-1- WO 2005/037279 PCT/US2O04/033732 1_2 0,4' -BIPEPIDIN-1'-YL)-1- (PHENYL) -ETHYL ! CYCLCHEXANOL DERIVATIVES AS MONOAHINE REUPTAKE MODULATORS FOR THE TREATMENT OF VISONCTOR SYMPTOMS CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Application No. 10/ filed October 12, 2004, which claims the benefit of U.S. Application Nos. 60/511,042 filed October 14, 2003, 60/561,448 filed .April 12, 2004, and 60/570,026 filed May 11, 2004, the entire disclosures of which are herein incorporated by reference. FIELD OF THE INVENTION [0002] The present invention relates to substituted N-heterocycle derivatives, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nerylus system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof. BACKGROUND OF THE INVENTION [0003] Vasomotor symptoms (VMS), referred to as hot flushes and night sweats, are the most common symptoms associated with menopause, occurring in 60% to 80% of all women following natural or surgically-induced menopause. VMS are likely to be an adaptive response of the central nerylus system (CNS) to declining sex steroids. To date, the most effective therapies for VMS are hormone-based treatments, including estrogens and/or some progestins. Hormonal treatments are very effective at alleviating VMS, but they are not appropriate for all women. It is well-recognized that VMS are caused by fluctuations of sex steroid levels and can be disruptive and disabling in both males and females. A hot flush can last up to -2- WO 2005/037279 PCT/US2004/033732 thirty minutes and vary in their frequency from several times a week to multiple occurrences per day. The patient experiences a hot flash as a sudden feeling of heat that spreads quickly from the face to the chest and back and then over the rest of the body. It is usually accompanied by outbreaks of profuse sweating. It may sometimes occur several times an hour, and it often occurs at night. Hot flushes and outbreaks of sweats occurring during the night can cause sleep deprivation. Psychological and emotional symptoms observed, such as nerylusness, fatigue, irritability, insomnia, depression, memory loss, headache, anxiety, nerylusness or inability to concentrate are considered to be caused by the sleep deprivation following hot flush and night sweats (Kramer et al., In: Murphy et al., 3'd Int'l Symposium on Recent Advances in Urological Cancer Diagnosis and Treatment-Proceedings, Paris, France: SCI: 3-7 0992)). [0004] Hot flushes may be even more severe in women treated for breast cancer for several reasons: 1) many surviylrs of breast cancer are given tamoxifen, the most prevalent side effect of which is hot flush, 2) many women treated for breast cancer undergo premature menopause from chemotherapy, 3) women with a history of breast cancer have generally been denied estrogen therapy because of concerns about potential recurrence of breast cancer (Loprinzi, et al., Lancet, 2000, 356(9247): 2059-2063). [0005] Men also experience hot flushes following steroid hormone (androgen) withdrawal. This is true in cases of age-associated androgen decline (Katovich, et al., Proceedings of the Society for Experimental Biology & Medicine, 1990, 193(2): 129-35) as well as in extreme cases of hormone deprivation associated with treatments for prostate cancer (Berendsen, et al., European Journal of Pharmacology, 2001, 4190): 47-54. As many as one-third of these patients will experience persistent and frequent symptoms severe enough to cause significant discomfort and inconvenience. [0006] The precise mechanism of these symptoms is unknown but generally is thought to represent disturbances to normal homeostatic mechanisms controlling thermoregulation and vasomotor activity (Kronenberg et al., "Thermoregulatory -3- WO 2005/037279 PCT/U:S2004/033732 Physiology of Menopausal Hot Flashes: A Review," Can. J. Physiol. Pharmacol., 1987565:1312-1324). [0007] The fact that estrogen treatment {e.g. estrogen replacement therapy) relieves the symptoms establishes the link between these symptoms and an estrogen deficiency. For example, the menopausal stage of life is associated with a wide range of other acute symptoms as described above and these symptoms are generally estrogen responsive. [0008] It has been suggested that estrogens may stimulate the activity of both the norepinephrine (NE) and/or serotonin (5-HT) systems (J. Pharmacology & Experimental Therapeutics, 1986, 236(3) 646-652). It is hypothesized that estrogens modulate NE and 5-HT levels providing homeostasis in the thermoregulatory center cf the hypothalarnus. The descending pathways from the hypothalamus via brainstem/spinal cord and the adrenals to the skin are inyl]ved in maintaining normal skin temperature. The action of NE and 5-HT reuptake inhibitors is known to impinge on both the CNS and peripheral nerylus system (PNS). The pathophysiology of VMS is mediated by both central and peripheral mechanisms and, therefore, the interplay between the CNS and PNS may account for the efficacy of dual acting SRI/NRIs in the treatment of thermoregulatory dysfunction. In fact, the physiological aspects and the CNS/PNS inyl]vement in VMS may account for the lower doses proposed to treat VMS (Loprinzi, et al. Lancet, 2000, 356:2059-2063; Stearns et al., JAMA, 2003, 289:2827-2834) compared to doses used to treat the behavioral aspects of depression. The interplay of the CNS/PNS in the pathophysiology of VMS and the presented data within this document were used to support the claims that the norepinephrine system could be targeted to treat VMS. [0009] Although VMS are most commonly treated by hormone therapy (orally, transdermally, or via an implant), some patients cannot tolerate estrogen treatment (Berendsen, Maturitas, 2000, 36(3): 155-164, Fink et al., Nature, 1996, 383(6598): 306). In addition, hormone replacement therapy is usually not recommended for women or men with or at risk for hormonally sensitive cancers (e.g. breast or prostate cancer). Thus, non-hormonal therapies (e.g. fluoxetine, paroxetine [SRIs] -4- WO 20015/037279 PCT/US2004/033732 and clonidine) are being evaluated clinically. WO9944601 discloses a method for decreasing hot flushes in a human female by administering fluoxetine. Other options have been studied for the treatment of hot flashes, including steroids, alpha-adrenergic agonists, and beta-blockers, with varylng degree of success (Waldinger etal., Maturitas, 2000, 36(3): 165-168).a [0010] It has been reported that #a2.adrenergic receptors play a role in thermoregulatory dysfunctions (Freedman et al., Fertility & Sterility, 2000, 740): 20-3). These receptors are located both pre- and post-synaptically and mediate an inhibitory role in the central and peripheral nerylus system. There are four distinct subtypes of the adrenergicC2 receptors, i.e., are #a2A, #a2B. and #a2D (Mackinnon et al., TIPS, 1994, 15: 119; French, Pharmacol. Ther., 1995, 68: 175). It has been reported that a non-select #a2-adrenoceptor antagonist, ychimbinc, induces #a flush and an #a2-adrenergic receptor agonist, clonidine: alleviates the yohimbine effect (Katovich, et al., Proceedings of the Society for Experimental Biology & Medicine, 1990, 193(2): 129-35, Freedman et al., Fertility & Sterility, 2000, 740): 20-3). Clonidine has been used to treat hot flush. However, using such treatment is associated with a number of undesired side effects caused by high doses necessary to abate hot flash described herein and known in the related arts. [0011] Given the complex multifaceted nature of thermoregulation and the interplay between the CNS and PNS in maintaining thermoregulatory homeostasis, multiple therapies and approaches can be developed to target vasomotor symptoms. The present invention focuses on novel compounds and compositions containing these compounds directed to these and other important uses. SUMMARY OF THE INVENTION [0012] The present invention is directed to substituted N-heterocycle derivatives, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, -5- WO 2005/0J7279 PCT/US2004/033732 gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia synorome, nerylus system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof. [0013] In one embodiment, the present invention is directed to compounds of formula I: I or a pharmaceutically acceptable salt thereof; wherein: A is phenyl, naphthyl, thiophenyl, pyridinyl, furanyl, benzofuranyl, isobenzofuranyl, xanthenyl, pyrrolyl, indolizinyl, isoindolyl, indolyl, or benzothiophenyl, where 1 to 3 carbon atoms of said A is optionally replaced with a nitrogen atom; U is N or O; W is H or OR8; R1 and R2 are, independently, H, OH, alkyl, alkoxy, halo, trifluoromethyl, alkanoyloxy, methylenedioxy, benzyloxy (optionally substituted with one or more R1), phenyloxy (optionally substituted with one or more R1), naphthyloxy (optionally substituted with one or more R1), phenylethoxy (optionally substituted with one or more R1), phenoxyethoxy (optionally substituted with one or more R1), -6- W0 2005/037279 PCT/US2004/033732 naphthylmethoxy (optionally substituted with one or more R1), phenylcarbonylamino (optionally substituted with one or more R1), phenylaminocarbonyl (optionally substituted with one or more R1), nitro, trifluoromethoxy, nitrile, alkenyl, alkynyl, sulfoxide, sulfonyl, sulfonamido, phenyl (optionally substituted with one or more R1), heteroaryl (optionally substituted with one or more R1), heteroaryloxy (optionally substituted with one or more R1), or heteroarylmethyloxy (optionally substituted with one or more R1); R3 and R4 are, independently, H, (C1-C6)alkyl, benzyl (optionally substituted with one or more R1), naphthylmethyl (optionally substituted with one or more R1), phenyl(C2-Ce)alkyl, heteroarylmethyl, cycloalkyl, cycloalkenyl, or cycloalkylmethyl (where any carbon atom of said cycloalkylmethyl may be optionally replaced with N, S, or O), provided that, when U is O, one of R3 and R4 is absent; or when U is N, R3 and R4, together with U, form a ring with 3 to 7 ring carbon atoms, and any ring carbon atom can be optionally replaced with N, S, or O: R5 is H, (C1-C6)alkyl, halo, or trifluoromethyl; or R3 and R5, together with U, form a ring with 3 to 7 ring carbon atoms, and any ring carbon atom can be optionally replaced with N, S, or O; R6 and R7 are, independently, (C1-C6)alkyl or (C3-C6)cycloalkyl; or R6 and R7 can together form a ring of 4 to 8 carbon atoms; where any carbon atom of said R6 and R7 may be optionally replaced with N, S, orO; where R6 and R7 may be optionally substituted with R5 or OH; or where R6 and R7 can form a ring with 4 to 8 carbons fused onto a cycloalkyl ring of 4 to 6 carbon atoms; R8 is H, (C1-C4)alkyl, or (d-C4)alkyl-C(=O); t is 1, 2, or 3; x is 0, 1, or 2; y is 0, 1, or 2; and z is 0, 1, or 2. [0014] In yet other embodiments, the present invention is directed to compositions, comprising: a. at least one compound of formula I; and -7- WO 2005/037279 PCT/US2004/033732 b. at least one pharmaceutically acceptable carrier. [0015] In another embodiment, the present invention is directed to methods for treating or preventing a condition ameliorated by monoamine reuptake in a subject in need thereof, comprising the step of: administering to said subject an effective amount of a compound of formula I or pharmaceutically acceptable salt thereof. The conditions ameliorated by monoamine reuptake include those selected from the group consisting of vasomotor symptoms, sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nerylus system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyaigia, pain, diabetic neuropathy, and combinations thereof. [0016] In another embodiment, the present invention is directed to methods for treating or preventing vasomotor symptoms in a subject in need thereof, comprising the step of: administering to said subject an effective amount of at least one compound of formula I or pharmaceutically acceptable salt thereof. [0017] In yet another embodiment, the present invention is directed to methods for treating or preventing a depression disorder in a subject in need thereof, comprising the step of: administering to said subject an effective amount of at least one compound of formula I or pharmaceutically acceptable salt thereof. [0018] In yet other embodiments, the present invention is directed to methods for treating or preventing sexual dysfunction in a subject in need thereof, comprising the step of: administering to said subject an effective amount of at least one compound of formula I or pharmaceutically acceptable salt thereof. -8- WO 2005/037279 PCT/US2004/033732 [0019] In further embodiments, the present invention is directed to methods for treating or preventing pain in a subject in need thereof, comprising the step of: administering to said subject an effective amount of at least one compound of formula I orpharmaceutically acceptable salt thereof. [0020] In another embodiment, the present invention is directed to methods for treating or preventing gastrointestinal or genitourinary disorder, particularly stress incontinence or urge urinary incontinence, in a subject in need thereof, comprising the step of: administering to said subject an effective amount of a compound of formula I or pharmaceutically acceptable salt thereof. [0021] In another embodiment, the present invention is directed to methods for treating or preventing chronic fatigue syndrome in a subject in need thereof, comprising the step of: administering to said subject an effective amount of a compound of formula I or pharmaceutically acceptable salt thereof. [0022] In another embodiment, the present invention is directed to methods for treating or preventing fibromylagia syndrome in a subject in need thereof, comprising the step of: administering to said subject an effective amount of a compound of formula I or pharmaceutically acceptable salt thereof. BRIEF DESCRIPTION OF THE DRAWINGS [0023] The invention can be more fully understood from the following detailed description and the accompanylng drawings that form a part of this application. [0024] Figure 1 is an overview of estrogen action on norepinephrine/serotonin mediated thermoregulation. [0025] Figure 2 is a schematic representation of the interactions of -9- WO 2005/037279 PCT/U S2004/O33732 norepinephrine and serotonin and their respective receptors (5-HT2a. #a1 and #a2-adrerngic). DETAILED DESCRIPTION OF THE INVENTION [0026] The present invention is directed to substituted N-heterocycle derivatives, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nerylus system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof. [0027] The following definitions are provided for the full understanding of terms and abbreviations used in this specification. [0028] As used herein and in the appended claims, the singular forms "a," "an," and "the" include the plural reference unless the context clearly indicates otherwise. Thus, for example, a reference to "an antagonist" includes a plurality of such antagonists, and a reference to "a compound" is a reference to one or more compounds and equivalents thereof known to those skilled in the art, and so forth. [0029] The abbreviations in the specification correspond to units of measure, techniques, properties, or compounds as follows: "min" means minutes, "h" means hour(s), "uL" means microliter(s), "mL" means milliliter(s), "mM" means millimolar, "M" means molar, "mmole" means millimole(s), "cm" means centimeters, "SEM" means standard error of the mean and "IU" means International Units. "A°C" and A "ED50 value" means dose which results in 50% alleviation of the observed condition or effect (50% mean maximum endpoint). [0030] "Norepinephrine transporter" is abbreviated NET. -10- WO 2005/037279 PCT/US2004/033732 "Human norepinephrine transporter" is abbreviated hNET. "Serotonin transporter" is abbreviated SERT. "Human serotonin transporter" is abbreviated hSERT. "Norepinephrine reuptake inhibitor" is abbreviated NRI. "Selective norepinephrine reuptake inhibitor" is abbreviated SNRI. "Serotonin reuptake inhibitor" is abbreviated SRI. "Selective serotonin reuptake inhibitor" is abbreviated SSRI. "Norepinephrine" is abbreviated NE. "Serotonin is abbreviated 5-HT. "Subcutaneous" is abbreviated sc. "Intraperitoneal" is abbreviated ip. "Oral" is abbreviated po. [0031] In the context of this disclosure, a number of terms shall be utilized. The term "treatment" as used herein includes preventative {e.g., prophylactic), curative or palliative treatment and "treating" as used herein also includes preventative, curative and palliative treatment. [0032] The term "effective amount," as used herein, refers to an amount effective, at dosages, and for periods of time necessary, to achieve the desired result with respect to prevention or treatment of vasomotor symptoms, depression disorders, sexual dysfunction, or pain. In particular with respect to vasomotor symptoms, "effective amount" refers to the amount of compound or composition of compounds that would increase norepinephrine levels to compensate in part or total for the lack of steroid availability in subjects subject afflicted with a vasomotor symptom. Varylng hormone levels will influence the amount of compound required in the present invention. For example, the pre-menopausal state may require a lower level of compound due to higher hormone levels than the peri-menopausal state. [0033] It will be appreciated that the effective amount of components of the present invention will vary from patient to patient not only with the particular compound, component or composition selected, the route of administration, and the ability of the components (alone or in combination with one or more combination drugs) to elicit a -11- WO 2005/037279 PCT/US2U04/033732 desired response in the individual, but also with factors such as the disease state or severtfy.of the condition to be alleviated, hormone levels, age, sex, weight of the individual, the state of being of the patient, and the severity of the pathological condition being treated, concurrent medication or special diets then being followed by the particular, patient, and other factors which those skilled in the art will recognize, with the appropriate dosage ultimately being at the discretion of the attendant physician. Dosage regimens may be adjusted to provide the improved therapeutic response. An effective amount is also one in which any toxic or detrimental effects of the components are outweighed by the therapeutically beneficial effects. [0034] Preferably, the compounds of the present invention are administered at a dosage and for a iinie such that the number of hot flushes is reduced as compared to the number of hot flushes prior to the start of treatment. Such treatment can also be beneficial to reduce the overall severity or intensity distribution of any hot flushes still experienced, as compared to the severity of hot flushes prior to the start of the treatment. With respect to depression disorders, sexual dysfunction, and pain, the compounds of the present invention are administered at a dosage and for a time such that there is the prevention, alleviation, or elimination of the symptom or condition. [0035] For example, for an afflicted patient, compounds of formula I may be administered, preferably, at a dosage of from about 0.1 mg/day to about 200 mg/day, more preferably from about 1 mg/day to about 100 mg/day and most preferably from about 1 mg/day to 50 mg/day for a time sufficient to reduce and/or substantially eliminate the number and/or severity of hot flushes or symptom or condition of the depression disorder, sexual dysfunction, or pain. [0036] The terms "component," "composition of compounds," "compound," "drug," or "pharmacologically active agent" or "active agent" or "medicament" are used interchangeably herein to refer to a compound or compounds or composition of matter which, when administered to a subject (human or animal) induces a desired pharmacological and/or physiologic effect by local and/or systemic action. -12- WO 2005/037279 PCT/US2004/033732 [0037] The terms "component", "drug" or "pharmacologically active agent" or "active agent" or "medicament" are used interchangeably herein to refer to a compound or compounds or composition of matter which, when administered to an organism (human or animal) induces a desired pharmacologic and/or physiologic effect by local and/or systemic action. [0038] The term "modulation" refers to the capacity to either enhance or inhibit a functional property of a biological activity or process, for example, receptor binding or signaling activity. Such enhancement or inhibition may be contingent on the occurrence of a specific event, such as activation of a signal transduction pathway and/or may be manifest only in particular cell types. The modulator is intended to comprise any compound, e.g., antibody, small molecule, peptide, oligopeptide, polypeptide, or protein, preferably small molecule, or peptide. [0039] As used herein, the term "inhibitor" refers to any agent that inhibits, suppresses, represses, or decreases a specific activity, such as serotonin reuptake activity or the norepinephrine reuptake activity. [0040] The term "inhibitor" is intended to comprise any compound, e.g., antibody, small molecule, peptide, oligopeptide, polypeptide, or protein, preferably small molecule or peptide, that exhibits a partial, complete, competitive and/or inhibitory effect on mammalian, preferably the human norepinephrine reuptake or both serotonin reuptake and the norepinephrine reuptake, thus diminishing or blocking, preferably diminishing, some or all of the biological effects of endogenous norepinephrine reuptake or of both serotonin reuptake and the norepinephrine reuptake. [0041] Within the present invention, the compounds of formula I may be prepared in the form of pharmaceutically acceptable salts. As used herein, the term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic acids, including inorganic salts, and organic salts. Suitable non-organic salts include inorganic and organic acids such as acetic, -13- WO 2005/037279 PCT/US2004/033732 benzenesulfonic. benzoic, camphorsulfonic, citric, ethenesulfonic, fumaric, gluconic, glutar.ftic, hydrobromic, hydrochloric, isethionic, lactic, malic, maleic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric acid, p-toluenesulfonic and the like. Particularly preferred are hydrochloric, hydrobromic, phosphoric, and sulfuric acids, and most preferably is the hydrochloride salt. [0042] "Administering," as used herein, means either directly administering a compound or composition of the present invention, or administering a prodrug, derivative or analog which will form an equivalent amount of the active compound or substance within the body. [0043] The term "subject" or "patient" refers to an animal including the human species that is treatable with the compositions, and/or methods of the present invention. The term "subject" or "subjects" is intended to refer to both the male and female gender unless one gender is specifically indicated. Accordingly, the term "patient" comprises any mammal which may benefit from treatment or prevention of vasomotor symptoms, depression disorders, sexual dysfunction, or pain, such as a human, especially if the mammal is female, either in the pre-menopausal, peri-menopausal, or post-menopausal period. Furthermore, the term patient includes female animals including humans and, among humans, not only women of advanced age who have passed through menopause but also women who have undergone hysterectomy or for some other reason have suppressed estrogen production, such as those who have undergone long-term administration of corticosteroids, suffer from Cushing's syndrome or have gonadal dysgenesis. However, the term "patient" is not intended to be limited to a woman. [0044] The terms "premature menopause" or "artificial menopause" refer to ovarian failure of unknown cause that may occur before age 40. It may be associated with smoking, living at high altitude, or poor nutritional status. Artificial menopause may result from oophorectomy, chemotherapy, radiation of the pelvis, or any process that impairs ovarian blood supply. -14- WO 2005/037279 PCT/US2004/033732 [0045] The term "pre-menopausar means before the menopause, the term "peri-menopausal" means during the menopause and the term "post-menopausal" means after the menopause. "Ovariectomy" means removal of an ovary or ovaries and can be effected according to Merchenthaler etal, Maturitas, 1998, 30(3): 307-316. [0046] "Side effect" refers to a consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other then the one sought to be benefited by its administration. In the case, for example, of high doses of NRIs or NRI/SRI compounds alone, the term "side effect" may refer to such conditions as, for example, ylmiting, nausea, sweating, and flushes (Janowsky, et al., Journal of Clinical Psychiatry, 1984, 4500 Pt 2): 3-9). [0047] "Alkyl," as used herein, refers to an aliphatic hydrocarbon chain o[1 to about 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably, 1 to 6 carbon atoms, and even more preferably, 1 to 4 carbon atoms and includes straight and branched chains such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neo-pentyl, n-hexyl, and isohexyl. Lower alkyl refers to alkyl having 1 to 4 carbon atoms. [0048] "Alkoxy," as used herein, refers to the group R-O- where R is an alkyl group o[1 to 6 carbon atoms. [0049] "Alkoxycarbonyl," as used herein, refers to the group R-O-C(=O)- where R is an alkyl group o[1 to 6 carbon atoms. [0050] "Alkanoyl," as used herein, refers to the group R-C(=O)- where R is an alkyl group o[1 to 6 carbon atoms. [0051] "Alkanoyloxy," as used herein, refers to the group R-C(=O)-O- where R is an alkyl group o[1 to 6 carbon atoms. -15- WO 2005/037279 PCT/US2004/033732 [0052] "Alkylaminocarbonyl," as used herein, refers to the group R-NH-C(=O)-where-R is an alkyl group o[1 to 6 carbon atoms. [0053] "Alkylcarbonylamino," as used herein, refers to the group R-C(=O)-NH where R is an alkyl group o[1 to 6 carbon atoms. [0054] "Alkenyl" or "olefinic," as used herein, refers to an alkyl group of at least two carbon atoms having one or more double bonds, wherein alkyl is as defined herein. Alkenyl groups can be optionally substituted with one or more R1, as defined herein. [0055] "Alkynyl," as used herein, refers to an alkyl group of at least two carbon atoms having one or more triple bonds, wherein alkyl is as defined herein. Alkynyl groups can be optionaiiy substituted with one or more R1, as defined herein. [0056] "Aryl" as used herein, refers to an optionally substituted, mono-, di-, tri-, or other multicyclic aromatic ring system having from about 5 to about 50 carbon atoms (and all combinations and subcombinations of ranges and specific numbers of carbon atoms therein), with from about 6 to about 10 carbons being preferred. Non-limiting examples include, for example, phenyl, naphthyl, anthracenyl, and phenanthrenyl. Aryl may be optionally substituted with one or more R1, as defined herein. [0057] "Heteroaryl," as used herein, refers to an optionally substituted, mono-, di-, tri-, or other multicyclic aromatic ring system that includes at least one, and preferably from 1 to about 4 sulfur, oxygen, or nitrogen heteroatom ring members. Heteroaryl groups can have, for example, from about 3 to about 50 carbon atoms (and all combinations and subcombinations of ranges and specific numbers of carbon atoms therein), with from about 4 to about 10 carbons being preferred. Non-limiting examples of heteroaryl groups include, for example, pyrryl, fury I, pyridyl, 1,2,4-thiadiazolyl, pyrimidyl, thienyl, isothiazolyl, imidazolyl, tetrazolyl, pyrazinyl, pyrimidyl, quinolyl, isoquinolyl, thiophenyl, benzothienyl, isobenzofuryl, pyrazolyl, indolyl, purinyl, carbazolyl, bcnzimidazolyl, and isoxazolyl. Heteroaryl may be optionally substituted with one or more R1, as defined herein. -16- WO 2005/037279 PCT/US20O4/033732 [0058] "Heterocyclic ring/' as used herein, refers to a stable 5- to 7-membered monocyclic or bicyclic or 7- to 10-membered bicyclic heterocyclic ring that is saturated, partially unsaturated or unsaturated (aromatic), and which contains carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, O and S and including any bicyclic group in which any of the above defined heterocyclic rings is fused to a benzene ring. The nitrogen and sulfur heteroatoms may optionally be oxidized. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. If specifically noted, a nitrogen atom in the heterocycle may optionally be quatemized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds one, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than one. Examples of heterocycles include, but are not limited to, 1H-indazole, 2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl, 4-piperidonyl, 4aH-carbazole, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, carbazolyl, 4H-carbazolyl, a-, (3-, or v-carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1 H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl., oxazolyl, oxazolidinylpyrimidinyl, phenanthridinyl, phenanthrolinyl, phenoxazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, carbolinyl, tetrahydrofuranyl, -17- WO 2005/037279 PCT/US2004/033732 tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4 thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazoiyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, xanthenyl. Preferred heterocycles include, but are not limited to, pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, indolyl, benzimidazolyl, 1 H-indazolyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, or isatinoyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles. [0059] "Heteroarylmethyl," as used herein, refers to the group R-CH2- where R is a heteroaryl group, as defined herein. [0060] "Heteroarylmethyloxy," as used herein, refers to the group R-CH2-0- where R is a heteroaryl group, as defined herein. [0061] "Heteroaryloxy," as used herein, refers to the group R-O- where R is a heteroaryl group, as defined herein. [0062] "Heteroarylmethyloxy," as used herein, refers to the group R-CH2-0- where R is a heteroaryl group, as defined herein. [0063] "Cycloalkyl," as used herein, refers to an optionally substituted, alkyl group having one or more rings in their structures having from 3 to about 20 carbon atoms (and all combinations and subcombinations of ranges and specific numbers of carbon atoms therein), with from 3 to about 10 carbon atoms being preferred. Multi-ring structures may be bridged or fused ring structures. Groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, 2-[4-isopropyl-1 -methyl-7-oxa-bicyclo[2.2.1 ]heptanyl], 2-[1,2,3,4-tetrahydro-naphthalenyl], and adamantyl. Cycloalkyl may be optionally substituted with one or more R1, as defined herein. [0064] "Cycloalkylmethyl," as used herein, refers to the group R-CH2- where R is a cycloalkyl group, as defined herein. -18- WO 2005/0J7279 PCT/US2004/033732 [0065] "Cycloalkenyl," as used herein, refers to an optionally substituted, alkene group having one or more rings in their structures having from 3 to about 20 carbon atoms (and all combinations and subcombinations of ranges and specific numbers of carbon atoms therein), with from 3 to about 10 carbon atoms being preferred. Multi-ring structures may be bridged or fused ring structures. Groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclooctenyl. Cycloalkenyl may be optionally substituted with one or more R1, as defined herein. [0066] "Cycloalkenylmethyl," as used herein, refers to the group R-CH2- where R is a cycloalkenyl group, as defined herein. [0067] "Sulfoxide," as used herein, refers to a compound or moiety containing the group -S(=O)-. [0068] "Sulfonamido," as used herein, refers to a moiety containing the group -S(O)2-NH-. [0069] "Sulfonyl," as used herein, refers to a moiety containing the group -S(O)2-. [0070] "Halo" or "halogen," as used herein, refers to chloro, bromo, fluoro, and iodo. [0071] In one embodiment, the present invention is directed to compounds of formula I: -19- WO 2005/037279 PCT/US2004/033732 or a pharmaceutically acceptable salt thereof; wherein: A is phenyl, naphthyl, thiophenyl, pyridinyl, furanyl, benzofuranyl, isobenzofuranyl, xanthenyl, pyrrolyl, indolizinyl, isoindolyl, indolyl, or benzothiophenyl, where 1 to 3 carbon atoms of said A is optionally replaced with a nitrogen atom; U is N or O; W is H or OR8; R1 and R2 are, independently, H, OH, alkyl, alkoxy, halo, trifluoromethyl, alkanoyloxy, methylenedioxy, benzyloxy (optionally substituted with one or more R1), phenyloxy (optionally substituted with one or more R1), naphthyloxy (optionally substituted with one or more R1), phenylethoxy (optionally substituted with one or more R1), phenoxyethoxy (optionally substituted with one or more R1), naphthylmethoxy (optionally substituted with one or more R1), phenylcarbonylamino (optionally substituted with one or more R1), phenylaminocarbonyl (optionally substituted with one or more R1), nitro, trifluoromethoxy, nitrite, alkenyl, alkynyl, sulfoxide, sulfonyl, sulfonamido, phenyl (optionally substituted with one or more R1), heteroaryl (optionally substituted with one or more R1), heteroaryloxy (optionally substituted with one or more R1), or heteroarylmethyloxy (optionally substituted with one or more R1); -20- WO 2005/037279 PCT/US20O4/033732 R3 and R4 are, independently, H, (C-C5)alkyl, benzyl (optionally substituted with one;or more R1), naphthylmethyl (optionally substituted with one or more R1), phenyl(C2-C6)alkyl, heteroarylmethyl, cycloalkyl, cycloalkenyl, or cycloalkylmethyl (where any carbon atom of said cycloalkylmethyl may be optionally replaced with N, S, or O), provided that, when U is O, one of R3 and R4 is absent; or when U is N, R3 and R4, together with U, form a ring with 3 to 7 ring carbon atoms, and any ring carbon atom can be optionally replaced with N, S, or O; R5 is H, (C1-C6)alkyl, halo, or trifluoromethyl; or R3 and R6, together with U, form a ring with 3 to 7 ring carbon atoms, and any ring carbon atom can be optionally replaced with N, S, or O; R6 and R7 are, independently, (C1-C6)alkyl or (C3-C6)cycloalkyl; or R6 and R7 can together form a ring of 4 to 8 carbon atoms; where any carbon atom of said R6 and R7 may be optionally replaced with N, S, or O; where R6 and R7 may be optionally substituted with R5 or OH; or where R6 and R7 can form a ring with 4 to 8 carbons fused onto a cycloalkyl ring of 4 to 6 carbon atoms; R8 is H, (CrC4)alkyl, or (C1C4)alkyl-C(=O); t is 1,2, or 3; x is 0, 1, or 2; y is 0, 1, or 2; and z is 0, 1, or 2. [0072] In certain preferred embodiments of compounds of formula I, A is phenyl, naphthyl, thiophenyl, pyridinyl, furanyl, benzofuranyl, isobenzofuranyl, xanthenyl, pyrrolyl, indolizinyl, isoindolyl, indolyl, or benzothiophenyl, where 1 to 3 carbon atoms of said A is optionally replaced with a nitrogen atom; U is N or O; W is H or OR8; R1 and R2 are, independently, H, OH, alkyl, alkoxy, halo, trifluoromethyl, alkanoyloxy, methylenedioxy, benzyloxy (optionally substituted with one or more R1), phenyloxy (optionally substituted with one or more R1), naphthyloxy (optionally -21- WO 2005/037279 PCT/US2OO4/033732 substituted with one or more R1), phenylethoxy (optionally substituted with one or more R1), phenoxyethoxy (optionally substituted with one or more R1), naphthylmethoxy (optionally substituted with one or more R1), phenylcarbonylamino (optionally substituted with one or more R1), phenylaminocarbonyl (optionally substituted with one or more R1), nitro, trifluoromethoxy, nitrile, alkenyl, alkynyl, sulfoxide, sulfonyl, sulfonamido, phenyl (optionally substituted with one or more R1), heteroaryl (optionally substituted with one or more R1), heteroaryloxy (optionally substituted with one or more R1), or heteroarylmethyloxy (optionally substituted with one or more R1); R3 and R4 are, independently, H, or (C1C6)alkyl; or R3 and R4, together with U, form a ring with 3 to 7 ring carbon atoms, and any ring carbon atom can be optionally replaced with N, S, or O; R5 is H, (C1-C6)alkyl, halo, or trifluoromethyl; or R3 and R5, together with U, form a ring with 3 to 7 ring carbon atoms, and any ring carbon atom can be optionally replaced with N, S, or O; R6 and R7 together form a ring of 4 to 8 carbon atoms; R8 is H; t is 1 or 2; x is 0, 1, or 2; y is 0, 1, or 2; and z isO. [0073] In certain preferred embodiments of compounds of formula I, A is phenyl, naphthyl, thiophenyl, pyridinyl, furanyl, benzofuranyl, isobenzofuranyl, xanthenyl, pyrrolyl, indolizinyl, isoindolyl, indolyl, or benzothiophenyl, where 1 to 3 carbon atoms of said A is optionally replaced with a nitrogen atom; U isN; W is OR8; R1 and R2 are, independently, H, OH, alkyl, alkoxy, halo, trifluoromeihyl, alkanoyloxy, methylenedioxy, benzyloxy (optionally substituted with one or more R1), phenyloxy (optionally substituted with one or more R1), naphthyloxy (optionally substituted with one or more R1), phenylethoxy (optionally substituted with one or -22- WO 2005/037279 PCT/US2004/033732 more R1), phenoxyethoxy (optionally substituted with one or more R1), naphthylmethoxy (optionally substituted with one or more R1), phenylcarbonylamino (optionally substituted with one or more R1), phenylaminocarbonyl (optionally substituted with one or more R1), nitro, trifluoromethoxy, nitrile, alkenyl, alkynyl, sulfoxide, sulfonyl, sulfonamido, phenyl (optionally substituted with one or more R1), heteroaryl (optionally substituted with one or more R1), heteroaryloxy (optionally substituted with one or more R1), or heteroarylmethyloxy (optionally substituted with one or more R1); R3 and R4 are, independently, H, or (C1-C6)alkyl; or R3 and R4, together with U, form a ring with 3 to 7 ring carbon atoms, R5 is H, (C1-C6)alkyl, halo, or trifluoromethyl; R5 and R7 together form a ring of 4 to 8 carbon atoms; R8 is H t is 1 x is 1, or 2; y is 1, or 2; and z is 0. [0074] In certain preferred embodiments, A is phenyl, naphthyl, thiophenyl, pyridinyl, furanyl, benzofuranyl, isobenzofuranyl, xanthenyl, pyrrolyl, indolizinyl, isoindolyl, indolyl, or benzothiophenyl. [0075] In certain preferred embodiments, U is N. In certain other preferred embodiments, U is O. [0076] In certain preferred embodiments, W is H. In certain other preferred embodiments, W is OR8, more preferably W is OH. [0077] In certain preferred embodiments, R1 and R2 are, independently, H, OH, alkyl (especially methyl, ethyl, propyl, and butyl), alkoxy (especially methoxy and ethoxy), halo, trifluoromethyl, alkanoyloxy, methylenedioxy, benzyloxy, phenyloxy, naphthyloxy, phenylethoxy, phenoxyethoxy, naphthylmethoxy, phenylcarbonylamino, -23- WO 2005/037279 PCT/US2004/033732 phenylaminocarbonyl, nitro, trifluoromethoxy, nitrile, alkenyl, alkynyl, sulfoxide, sulfunyl, sulfonamido, phenyl, heteroaryl, heteroaryloxy, or heteroarylmethyloxy. [0078] In certain preferred embodiments, R3 and R4 are, independently, H, (d-C6)alkyl (especially methyl, ethyl, propyl, and butyl), benzyl, naphthylmethyl, phenyl(C2-C6)alkyl, heteroarylmethyl, cycloalkyl, cycloalkenyl, or cycloalkylmethyl. [0079] In certain preferred embodiments, R3 and R4, together with U, form a ring with 3 to 7 ring carbon atoms. [0080] In certain preferred embodiments, R5 is H, (C1-C6)alkyl (especially methyl, ethyl, propyl, and butyl), halo (especially chloro, fluoro, and bromo), or trifluoromethyl. [0081] In certain preferred embodiments, R3 and R5, together with U, form a ring with 3 to 7 ring carbon atoms. [0082] In certain preferred embodiments, R6 and R7 are, independently, (C1 C6,)alkyl (especially methyl, ethyl, propyl, and butyl) or (C3-C6)cycloalkyl (especially cyclopropyl, cyclobutyl, and cyclohexyl). [0083] In certain preferred embodiments, R6 and R7 together with the carbon to which they are attached form a ring of 4 to 8 carbon atoms. [0084] In certain preferred embodiments, R8 is H, (d-C4)alkyl, or (d-d)alkyl-C(=O), more preferably, H or (d-d)alkyl, even more preferably, H or methyl. [0085] In certain preferred embodiments, t is 1. In certain preferred embodiments, t is 2. In certain preferred embodiments, t is 3. [0086] In certain preferred embodiments, x is 0. In certain preferred embodiments, x is 1. In certain preferred embodiments, x is 2. -24- WO 2005/037279 PCT/US2004/033732 [0087] In certain preferred embodiments, y is 0. In certain preferred embodiments, y is 1. -In certain preferred embodiments, y is 2. [0088] In certain preferred embodiments, z is 0. In certain preferred embodiments, z is 1. In certain preferred embodiments, z is 2. [0089] In certain preferred embodiments, A is phenyl, naphthyl or benzothienyl. [0090] In certain preferred embodiments, R1 and R2 are, independently, hydrogen, alkyl o[1-6 carbon atoms, alkoxy o[1-6 carbon atoms, halogen, trifluoromethyl, trifluoromethoxy, phenoxy-, phenylethoxy optionally substituted by an R1 substituent, benzyloxy and naphthylmethoxy. [0091] In certain preferred embodiments, W is OH. [0092] In certain preferred embodiments, R6 and R7 may form a ring of 4, 5, or 6 carbon atoms,e.g. cyclohexanol, optionally fused to a ring of 6 carbon atoms; said ring or rings being optionally substituted by up to four C1-C6 alkyl groups. [0093] In certain preferred embodiments, R6 and R7 may each represent a C1C6 alkyl groups, the same or different. [0094] An example of t is 1. An example of y is 1. An example of x is 0 or 1. An example of z is 0 or 1. [0095] In certain preferred embodiments, U may be for example N and R3 and R4 may be independently H or (C1-C6)alkyl or together with the nitrogen form a pyrrolidine or piperidine ring. [0096] In certain preferred embodiments, U may also represent O and for example one of R3 and R4 is absent, the other is (C1C6)alkyl. [0097] Preferred compounds of formula I include: -25- WO 2005/037279 PCT/US2004/033732 1-[2-0,4'-bipiperidin-1-yl)-1-(3-chlorophGnyl)ethyl]cyclohGxanol dihydrochloride; 1-[1-(3-chlorophenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]cyclohexanol dihydrochloride; 1 -[2-0,4'-bipiperidin-1 '-yl)-1 -(3-bromophenyl)ethyl]cyclohexanol dihydrochloride; 1 -[1 -(3-bromophenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)ethyl]cyclohexanol dihydrochloride; 1 -[2-0,4'-bipiperidin-1 '-yl)-1 -(3-bromo-4-methoxyphenyl)ethyl]cyclohexanol dihydrochloride; 1 -[1 -(3-bromo-4-methoxyphenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)ethyl]cyclohexanol dihydrochloride: 1 -[1 -(3,4-dichlorophenyl)-2-(4-pyrro!idin-1 -ylpiperidin-1 -yl)ethyl]cyclohexanol dihydrochloride: 1-{1-(3,4-dichlorophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride; 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3,4-dichlorophenyl)ethyl]cyclohexanol dihydrochloride; 1-[2-[(3S)-3-aminopyrrolidin-1-yl]-1-(3-chlorophenyl)ethyl]cyclohexanol dihydrochloride; 1 -{1 -(3-chlorophenyl)-2-[4-(methylamino)piperidin-1 -yl]ethyl}cyclohexanol dihydrochloride; 1-[2-(4-aminopiperidin-1-yl)-1-(3-bromophenyl)ethyl]cyclohexanol dihydrochloride; 1-{1-(3-bromophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride; 1 -{2-0,4'-bipiperidin-1 '-yl)-1 -[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride; 1-[2-0,4'-bipiperidin-1'-yl)-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride; 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3-bromo-4-methoxyphenyl)eihyl]cyclohexanol dihydrochloride; 1 -{2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)-1 -[3-(trif luoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride; -26- WO 2005/037279 PCT/US2004/033732 1 -{1 -{3-bromo-4-mefhoxyphenyl)-2-|4-(methylamino)piperidin-1 -y!]ethyf}cyclohexa dihydfochloride; 1 -{2-[4-(methylamino)piperidin-1 -yl]-1 -[3-(trif Iuoromethy!)phenyl]cthyl}cyc!ohexani dihydrochloride; 1 -[1 -(2-naphthyl)-2-(4-pyrrolidin-1 -yfpiperidin-1 -y!)ethyl]cyclohexano! dihydrochlor 1 -[2-(4-aminopiperidin-1 -yl)-1 -(2-naphthyl)ethyl]cyciohexanol dihydrochloride; 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3-chlorophenyl)ethyl]cyciohexanol dihydrochloride 1 -{1 -(3-chlorophenyl)-2-[4-(dime(hylamino)piperidin-1 -yl]ethyl}cyclohexanol dihydrochloride; 1 -{2-(4-aminopipcridin-1 -yl)-1 -[3-(trifiuoromethy!)phenyl]ethyl}cyclohexano! dihydrochloride; 1-[2-(4-aminopiperidin-1-yl)-1-(1-naphthyl)ethyl]cyclobutanol dihydrochloride; 1-[2-[4-(methylamino)piperidin-1-yl]-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride; 1 -[2-(4-aminopiperidin-1 -yl)-1 -(1 -naphthyl)ethyl]cyclohexane; 1 -{2-[(3R)-3-(methy!amino)piperidin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl] ethyl}cyclohexanol dihydrochloride; 1 -{2-[(3R)-3-aminopiperidin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl] ethyljcyclohexanol dihydrochbride; 1-{2-{(3R)-3-(dimethylamino)piperidin-1-yl]-1-[3-(trifluoromethoxy)pheny!] ethyl}cyclohexanol dihydrochloride; 1 -{2-{{3S)-3-(methylamino)piperidin-1 -yl]-1 -[3-(tnfluoromethoxy)phenyl] ethyl}cyclohexanol dihydrochloride; 1-{2-[{3S)-3-aminopiperidin-1-yl]-1-[3-(trifluoromelhoxy)phenyl] ethyl}cyclohexanol dihydrochloride; 1-{2-[(3S)-3-(dimethy!amino)piperidin-1-yl]-1-{3-(tnfluoromethoxy)pheny!] ethyljcyclohexano! dihydrochforide; 1 -{1 -[4-{benzyloxy)-3-chlorophenyl]-2-[(3R)-3-(methylamino)piperidin-1 -yl]ethyl}cyclohexanol dihydrochloride; 1 -{2-[(3R)-3-aminopiperidin-1 -yl]-1 -[4-(benzyloxy)-3-chIorophenyl]ethyl} cyclohexanol dihydrochloride; 1 -{1 -[4-(benzyloxy)-3-chlorophenyl]-2-[(3R)-3-(dimethylamino)piperidin-1-yljethyl}cyclohexanol dihydrochloride; -27- WO 2005/037279 PCT/US2004/033732 1-{1-[4-(benzyloxy)-3-chlorophenyl]-2-[(3S)-3-(methylamino)piperidin-1-yl]ethyl)cyclohexanol dihydrochloride; 1-{2-[(3S)-3-aminopiperidin-1-yl]-1-[4-(benzyloxy)-3-chlorophenyljethyl} cyclohexanol dihydrochloride; 1-{1-[4-(benzyloxy)-3-chlorophenyl]-2-[(3S)-3-(dimethylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride; 1 -{1 -(3-chlorophenyl)-2-[(3S)-3-(methylamino)pyrrolidin-1 -yljethyl} cyclohexanol dihydrochloride; 1-{1-(3-chlorophenyl)-2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]ethyl} cyclohexanol dihydrochloride; 1-{1-(3-chlorophenyl)-2-[(3R)-3-(methylamino)pyrrolidin-1-yljethyl} cyclohexanol dihydrochloride; 1-[2-[(3R)-3-arr.inopyrro!idin-1-y!]-1-(3-ch!oropheny!)ethyl]cyclohexanol dihydrochloride; 1 -{1 -(3-chlorophenyl)-2-[(3R)-3-(dimethylamino)pyrrolidin-1 -yl]ethyl}cyclohexanol dihydrochloride; 1 -[2-[(3S)-3-(methylamino)pyrrolidin-1 -yl]-1 -(2-naphthyl)ethyl]cyclohexanol dihydrochloride; 1-[2-[(3S)-3-aminopyrrolidin-1-yl]-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride; 1-[2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride; 1-[2-[(3S)-3-(methylamino)pyrrolidin-1-yl]-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride; 1 -[2-[(3S)-3-aminopyrrolidin-1 -yl]-1 -(1 -naphthyl)ethyl]cyclohexanol dihydrochloride; 1-[2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride; 1 -{1 -[4-(benzyloxy)-3-chlorophenyl]-2-[(3S)-3-(methylamino)pyrrolidin-1 -yl]ethyl}cyclohexanol dihydrochloride; 1 -{2-[(3S)-3-aminopyrrolidin-1 -yl]-1 -[4-(benzyloxy)-3-chlorophenyl]ethyl}cyclohexanol dihydrochloride; -28- WO 2005/037279 PCT/US2004/033732 1-{1-[4-(benzyloxy)-3-chlorophenyl]-2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]ethyj]cyclohexanol dihydrochloride; 1-{1-[4-(benzyloxy)phenyl]-2-[(3S)-3-(methylamino)pyrrolidin-1-yl]ethyl}cyclohexanol dihydrochloride; 1-{2-[(3S)-3-aminopyrrolidin-1-yl]-1-[4-(benzyloxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{1 -[4-(benzyloxy)phenyl]-2-[(3S)-3-(dimethylamino)pyrrolidin-1 -yl]ethyl}cyclohexanol dihydrochloride; 1 -{2-[(3S)-3-(methylamino)pyrrolidin-1 -yl]-1 -[3-(lrifluoromefhoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{2-[(3S)-3-aminopyrrolidin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{2-[(3S)-3-(dimethylamino)pyrrolidin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{2-[(3R)-3-(methylamino)pyrrolidin-1 -yl]-1 -[3-(trifluoromelhoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{2-[(3R)-3-(dimethylamino)pyrrolidin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl]e(hyl}cyclohexanol dihydrochloride; 1 -{2-[(3S)-3-(methylamino)pyrrolidin-1 -yl]-1 -[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride; 1-{2-[(3S)-3-aminopyrrolidin-1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride; 1-{2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride; 1-{2-[(3R)-3-(methylamino)pyrrolidin-1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride; 1-{2-[(3R)-3-aminopyrrolidin-1-yl]-1-[3-(trifluoromethy!)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{2-[(3R)-3-(dimethylamino)pyrrolidin-1 -yl]-1 -[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride; 1-[2-(3-chlorophenyl)-2-cyclopentylethyl]-N-methylpiperidin-4-amine dihydrochloride; -29- WO 2005/037279 PCT/US2004/033732 1-[2-(3-chlorophenyl)-2-cyclopentylethyl]-N,N-dimethylpipendin-4-amine dihydrochloride; 1-[2-(3-chlorophenyl)-2-cyclohexylethyl]-N-methylpiperidin-4-amine dihydrochloride; 1-[2-(3-chlorophenyl)-2-cyclohexylethyl]-N,N-dimethylpiperidin-4-amine dihydrochloride; 1-[2-(3-chlorophenyl)-2-cycloheptylethyl]-N-methylpiperidin-4-amine dihydrochloride; 1-[2-(3-chlorophenyl)-2-cycloheptylethyl]-N,N-dimethylpiperidin-4-amine dihydrochloride; 2-[2-(4-aminopiperidin-1-yl)-1-(3-chlorophenyl)ethyl]cyclohexanol dihydrochloride; 1 -{2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethoxy)phenyl]ethyl} piperidin-4-ol hydrochloride: 1-[2-[4-(benzyloxy)-3-chlorophenyl]-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-ol hydrochloride; 1-[1-[4-(benzyloxy)-3-chlorophenyl]-2-(4-methoxypiperidin-i-yl)ethyl]cyclohexanol hydrochloride; 4-(4-aminopiperidin-1-yl)-3-(3-chlorophenyl)-2-methylbutan-2-ol dihydrochloride; 3-(3-chlorophenyl)-4-[4-(dimethy)amino)piperidin-1-yl]-2-methylbutan-2-ol dihydrochloride; 1 -[2-(4-aminopiperidin-1 -yl)-1 -(5-methoxy-1 -benzothien-3-yl)ethyl]cyclohexanol dihydrochloride; 4-[2-(4-aminopiperidin-1-yl)-1-(3-chlorophenyl)ethyl]heptan-4-ol dihydrochloride; 1-{2-0,4'- bipiperidin-1'-yl)-1-[4-(trifluoromethoxy)phenyl]ethyl} cyclohexanol dihydrochloride; 1 -{2-(4-aminopiperidin-1 -yl)-1 -[4-(trifluoromethoxy)phenyl]ethyl} cyclohexanol dihydrochloride; 1 -{2-(4-aminopiperidin-1 -yl)-1 -[4-(tri{luoromethoxy) phenyljethyl} cyclobutanol dihydrochloride; -30- WO 2005/037279 PCT/US2004/033732 1-{2-(4-aminopiperidin-1-yl)-1-(4-phenoxyphenyl)elhyl]cyclohexanol dihydrochloride; 1 -[2-0,4'- bipiperidin-1 '-yl)-1 -[3-(phenoxyphenyl)elhyl]cyclchexanol dihydrochloride; 1-{2-(4-aminopiperidin-1-yl)-1-(3-phenoxyphenyl)ethyl]cyclohexanol dihydrochloride; 1-[1-(3-phenoxyphenyl)-2-(4-pyrrolidin-1-ytpiperidin-1-yl)ethyl] cyclohexanol dihydrochloride; 1 -[2-[4-(dimethylamino)piperidin-1 -yl]-1 -(2-naphthyl)ethyl]cyclohexanol dihydrochloride; 1 -{1 -(3-bromo-4-methoxyphenyl)-2-[4-(dimethylamino)piperidin-1 -yl]ethyl}cyclohexanol dihydrochloride; 1-{1-(3-bromopheny!)-2-[4-(d!methylarr.;r.c)piperidin-"!-yljethy!}cycioriexanoi dihydrochloride; 1 -{1 -(3,4-dichlorophenyl)-2-[4-(dimethylamino)piperidin-1 -yl]ethyl}cyclohexanol dihydrochloride; 1-{2-[4-(dimethylamino)piperidin-1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl} cyclohexanol dihydrochloride; 2-[2-(4-aminopiperidin-1 -yl)-1 -(3-chlorophenyl)ethyl]decahydro naphthalen-2-ol dihydrochloride; 1-[2-(4-aminopiperidin-1-yl)-1-(3-chlorophenyl)ethyl]-4-methylcyclo hexanol dihydrochloride; 1 -[1 -[4-(benzyloxy)-3-chlorophenyl]-2-(4-methoxypiperidin-1 -yl)ethyl]cyclohexanol; 1 -[2-(4-aminopiperidin-1 -yl)-1 -(6-methoxy-2-naphthyl)ethyl] cyclohexanol; 1-[2-[4-(dimethylamino)piperidin-1-yl]-1-(6-methoxy-2-naphthyl)ethyl] cyclohexanol; 1-{1-(6-methoxy-2-naphthyl)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol; 1 -[1 -(6-methoxy-2-naphlhyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)ethyl]cyclohexanol; 1 -[2-0,4'-bipiperidin-1 '-yl)-1 -(6-methoxy-2-naphthyl)ethyl]cyclohexanol; 1-[1S)-2-0,4'-bipiperidin-1'-yl)-1-(6-methoxy-2-naphthyl)ethyl] cyclohexanol; -31- WO 2O05/(»37279 PC T/US2004/033732 1-((1R)-2-0)4l-bipiperidin-i'-yl)-1-(6-melhoxy-2-naphthyl)ethyl] cyclohexanol; i-[(2S)-2-(3-chlorophenyl)-2-cyclohexylethyl]-N-methylpiperidin-4-amine; 1-[(2R)-2-(3-chlorophenyl)-2-cyclohexylethyl]-N-methylpiperidin-4-amine; 1-{(iS)-2-[4-(methylamino)piperidin-1-yl]-1-[3-(trifluoromethoxy) phenyl]ethyl}cyclohexanol; 1-{(iS)-2-[4-(dimethylamino)piperid;n-1-yl]-1-[3-(trifluoromethoxy) phenyl]ethyl}cyclohexanol; 1-{2-(4-morpholin-4-ylpiperidin-1-yl)-i-[3-(trifluoromethoxy)phenyl] ethyljcyclohexanol; 1-{0S)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)-1-{3-(trifluoromethoxy)phenyl] ethyljcyclohexanol; 1-{0S)-2-0,4'-bipiperidin-1'-yl)-1-[3-(trifluoromethoxy)phenyl] ethyljcyclohexanol; 1-[2-[(3R)-3-aminopyrroiidin-1-y!j-1-(2-riaphthyl)ethyl]cyciohexanoi; 1-[2-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-1-(2-naphthyl)ethyl] cyclohexanol; 1-[2-[(3R)-3-(methylamino)pyrrolidin-1-ylJ-1-(2-naphthyl)ethyl] cyclohexanol; 1-[2-[(3R)-3-aminopyrrolidin-1-yl]-1-(1-naphthyl)ethyl]cyclohexanol 1-[2-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-1-(1-naphthyl)ethyl] cyclohexanol; 1-[2-[(3R)-3-(methylamino)pyrrolidin-1-yl]-1-(1-naphthyl)ethyl] cyclohexanol; 1-{2-[(3R)-3-aminopyrrolidin-1-yl]-1-[4-(benzyloxy)phenyl] ethyljcyclohexanol; 1 -{1 -[4-(benzyloxy)phenyl]-2-[(3R)-3-(dimethylamino)pyrrolidin-1 -yl]ethyl}cyclohexanol; 1-{1-[4-(benzyloxy)phenyl]-2-[(3R)-3-(methylamino)pyrrolidin-1-yl]ethyl}cyclohexanol; 1-{2-[(3R)-3-aminopyrrolidin-1-yl]-1-[4-(benzyloxy)-3-chlorophenyl] ethyl}cyclohexanol; 1-{1-[4-(benzyloxy)-3-chlorophenyl]-2-[(3R)-3-(dimethylamino) pyrrolidin-1-yl]ethyl}cyclohexanol; 1-{1-[4-(benzyloxy)-3-chlorophenyl]-2-[(3R)-3-(methylamino)pyrrolidin-1-yl]ethyl}cyclohexanol; 1 -{2-[(3R)-3-aminopyrrolidin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl] ethyljcyclohexanol; 1-[1S)-2-[(3S)-3-aminopyrrolidin-1-yl]-1-(3-chlorophenyl)ethyl] cyclohexanol; -32- WO 2005/037279 PCT/IS2004/033732 1-[(1R)-2-[(3S)-3-aminopyrrolidin-1-yl]-1-(3-chlorophenyl)ethyl]cyclohexanol; l3R)-1-{2-0,4l-bipiperidin-1'-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}-3-methylcyclopentanol; 1-{2-(4-aminopiperidin-1-yl)-i-[4-(benzyloxy)-3-chlorophenyl]ethyl} cyclohexanol; 1 -{1 -[4-(benzyloxy)-3-chlorophenyl]-2-[4-(dimethylamino)piperidin-1 -yl]ethyl}cyclohexanol; 1 -{2-(4-aminopiperidin-1 -yl)-1 -[3-chloro-4-(2-naphthylmethoxy)phenyl] ethyljcyclohexanol; 1 -{1 -[3-chloro-4-(2-naphthylmethoxy)phenyl]-2-[4-(dimethylamino) piperidin-1 -yl]ethyl}cyclohexanol; 1-{2-(4-aminopiperidin-1-yl)-1-[4-(benzyloxy)-3-methoxyphenyl]ethyl} cyclohexanol: 1 -{1 -[4-(benzyloxy)-3-methoxyphenyl]-2-[4-(dimethylamino)piperidin-1 -yl]ethyl}cyclohexanol; 1-[2-0,4'-bipiperidin-1l-yl)-1-(3-chloro-4-methoxyphenyl)ethyl] cyclohexanol; 1-{2-0,4'-bipiperidin-1'-yl)-1-[4-(2-phenylethoxy)phenyl]ethyl} cyclohexanol; 1-(2-(i,4'-bipiperidin-1I-yl)-1-{4-[2-(4-methoxyphenyl)ethoxy] phenyl}ethyl)cyclohexanol; and pharmaceutically acceptable salts thereof. [0098] Some of the compounds of the present invention may contain chiral centers and such compounds may exist in the form of stereoisomers (i.e. enantiomersy. The present invention includes all such stereoisomers and any mixtures thereof including racemic mixtures. [0099] Racemic mixtures of the stereoisomers as well as the substantially pure stereoisomers are within the scope of the invention. The term "substantially pure," as used herein, refers to at least about 90 mole %, more preferably at least about 95 mole %, and most preferably at least about 98 mole % of the desired stereoisomer is present relative to other possible stereoisomers. Preferred enantiomers may be isolated from racemic mixtures by any method known to those skilled in the art, -33- WO 2005/037279 PCT/US2OO4/033732 including high performance liquid chromatography (HPLC) and the formation and crystarlization of chiral salts or prepared by methods described herein. See, for example, Jacques, et al., Enantiomers, Raccmates and Resolutions (Wiley Interscience, New York, 1981); Wilen, S.H., et al., Tetrahedron, 33:2725 0977); Eliel, E.L. Stereochemistry of Carbon Compounds, (McGraw-Hill, NY, 1962); Wilen, S.H. Tables of Resolving Agents and Optical Resolutions, p. 268 (E.L. Eliel, Ed., University of Notre Dame Press, Notre Dame, IN 1972). [0100] The present invention includes prodrugs of the compounds of formula I. "Prodrug," as used herein, means a compound which is convertible in viyl by metabolic means (e.g. by hydrolysis) to a compound of formula I. Various forms of prodrugs are known in the art, for example, as discussed in Bundgaard, (ed.), Design of Prodrugs, Elsevier 0985); Widder, et al. (ed.), Methods in Enzymology, yl]. 4, Academic Press 0385); Krogsgaard-Larsen, et al., (ed). "Design and Application of Prodrugs," Textbook of Drug Design and Development, Chapter 5, 113-191 0991), Bundgaard, et al., Journal of Drug Deliver Reviews, 1992, 8:1-38, Bundgaard, J. of Pharmaceutical Sciences, 1988, 77:285 et seq.; and Higuchi and Stella (eds.) Prodrugs as Novel Drug Delivery Systems, American Chemical Society 0975). [0101] Further, the compounds of formula I may exist in unsolvated as well as in solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the purpose of the present invention. [0102] This invention also provides processes for preparing compound of formula, which processes include one of the following: a) reducing a compound of formula -34- WO 2005/037279 PCT/US2O04/033732 wherein R1-7, x, y, z, t, A, U and W are as defined herein, to give a compound of formula I wherein W is OH; if necessary any reactive groups or sites being protected during the reaction by protecting groups and removed thereafter; or b) alkylating a compound of formula I herein R3 and/or R4 is hydrogen with an alkylating agent to give a compound of formula I wherein R3 and/or R4 is alkyl; or c) converting a compound of formula I having a reactive substituent group to a compound of formula I having a different substituent group; or d) converting a basic compound of formula I to a pharmaceutically acceptable salt or vice versa. [0103] The compounds of the present invention may be prepared in a number of ways well known to those skilled in the art. The compounds can be synthesized, for example, by the methods described below, or variations thereon as appreciated by the skilled artisan. All processes disclosed in association with the present invention are contemplated to be practiced on any scale, including milligram, gram, multigram, kilogram, multikilogram or commercial industrial scale. -35- WO 2005/037279 PCT/US2004/033732 [0104] As will be readily understood, functional groups present may contain protect/fig groups during the course of synthesis. Protecting groups are known per se as chemical functional groups that can be selectively appended to and removed from functionalities, such as hydroxyl groups and carboxyl groups. These groups are present in a chemical compound to render such functionality inert to chemical reaction conditions to which the compound is exposed. Any of a variety of protecting groups may be employed with the present invention. Protecting groups that may be employed in accordance with the present invention may be described in Greene, T.W. and Wuts, P.G.M., Protective Groups in Organic Synthesis 2d. Ed., Wiley & Sons, 1991. [0105] Compounds of the present invention are suitably prepared in accordance with the following general description and specific examples. Variables used are as defined for formula I, unless otherwise noted. The reagents used in the preparation of the compounds of this invention can be either commercially obtained or can be prepared by standard procedures described in the literature. In accordance with this invention, compounds of formula I are produced by the following reaction schemes (Scheme 1-6). -36- WO 2005/037279 PCT/US2004/033732 Scheme 1 where A is as previously described; V = R3, R4.H,orP; T = R3, R4. H, or P; P is an amine protecting group, preferably but not limited to tert-butoxycarbonyl; and R1, R2, [3- R4, R5. R6. R7, W, x, y, z are as previously described. [0106] Compounds of formula I can be prepared from compounds of formula VI via reduction followed by deprotection, where Y = P; otherwise the deprotection step is omitted (Scheme 1). Where P = tert-butoxycarbonyl. any conventional method for the deprotection of a carbamate can be utilized for this conversion. In accordance with the preferred embodiment of this invention, deprotection is carried out using a protic acid, i.e. hydrochloric acid. Reduction is performed using any conventional method of reducing an amide to an amine. In accordance with the preferred embodiment of this invention, the compounds of formula VI are treated with a solution of borane in tetrahydrofuran and heated at 70-80°C. If it is desired to produce compounds of formula I where Y = H and 2 = methyl, an extra equivalent of borane may be used to reduce the protecting group where P = alkoxycarbonyl. [0107] Compounds of formula VI can be prepared via the coupling of compounds of formula V with an appropriately substituted amine. The reaction is carried out by any conventional method for the activation of a carboxylic acid to form an amide. In the preferred embodiment of this invention, the carboxylic acid is treated with benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluoro phosphate in the presence of an appropriately amine and triethylamine. [0108] Compounds of formula V are prepared by reacting an appropriately substituted ketone with an aryl or heteroarylacetic acid of formula IV via an aldol reaction. The aryl or heteroarylacetic acids of formula IV can be either commercially obtained or are known compounds that can be prepared by standard procedures -37- WO 2005/037279 PCT/US2004/033732 described in the literature. Compounds of formula IV represent an organic acid having-an alpha carbon atom, so reaction with a ketone occurs at the alpha carbon atom of this carboxylic acid. This reaction is carried out by any conventional means of reacting the alpha carbon atom of a carboxylic acid with a ketone. Generally, in these aldol reactions, a ketone is reacted with the dianion of the acetic acid. The anion can be generated with a strong organic base such as lithium diisopropylamide, as well as other organic lithium bases. This reaction is performed in low boiling point solvents such as tetrahydrofuran at low temperatures from -80°C to about -500C being preferred. [0109] If it is desired to produce compounds of formula VIII where R3 and R4 = [0110] If is desired to form compounds of formula VII where R3 = as above and R4 = as above other than methyl (Scheme 3), they can be formed from methyl (Scheme 2), they can be formed from compounds of formula I via an alkylation with methyl iodide or via a reductive amination with formaldehyde. Any conventional method of alkylating a primary amine with methyl iodide can be utilized. In addition, any conventional method of performing a reductive amination can be utilized. In accordance with the preferred embodiment of this invention, a mixture of the amine and formaldehyde in formic acid is heated at 60°C-80°C. -38- WO 2005/037279 PCT/US2004/033732 compounds of formula I via an alkylation with an alkyl halide or via a reductive amination with an aldehyde or ketone. Any conventional method of alkylating a primary or secondary amine with an alkyl halide can be utilized. In addition, any conventional method of performing a reductive amination can be utilized. In accordance with the preferred embodiment of this invention, a mixture of the amine and an appropriately substituted aldehyde or ketone in methylene chloride is treated with trisacetoxyborohydride to form compounds of formula VIII. [0111] If it is desired to produce compounds of formula X where R, = nitrite, they can be formed from compounds of formula IX where P = an amine protecting group, preferably but not limited to tert-butoxycarbonyl. In the case where P = tert-butoxycarbonyl, any conventional method for the deprotection of a carbamate can be utilized for this conversion. In accordance with the preferred embodiment of this invention, deprotection is carried out using a protic acid, i.e. hydrochloric acid. [0112] Compounds of formula IX can be formed from compounds of formula VII where R1 = iodine or bromine and Y = P (see Scheme 1). Any conventional method for converting an aryl iodide or aryl bromide to an aryl nitrile can be utilized for this conversion. According to the preferred embodiment of this invention, the aryl bromide of formula VII is treated with zinc cyanide, 1, 1'- bis(diphenylphosphino)ferrocine, zinc dust, and catalytic -39- \YO 2005/037279 PCT/US2004/033732 tris(dibenzylideneacetone)dipalladium. This reaction is performed in high boiling point solvents such as N,N-dimethylformamide, under nitrogen, at elevated temperatures from 1002C to about 150pC being preferred. Compounds of formula VII are prepared as depicted in Scheme 1. If it is desired to form compounds of formula VIII from compounds of formula X, the procedure outlined in either Scheme 2 or Scheme 3 can be followed. [0113] Compounds of formula VII, where R1 = bromine or iodine and where Y = P (see Scheme 1), can also be used to form compounds of formula XII, where C = phenyl, substituted phenyl, heteroaryl, or substituted heteroaryl, if it is desired. Compounds of formula XII can be formed from compounds of formula VII where R1 = bromine or iodine via a cross-coupling reaction with either an aryl boronic acid or an aryl stannane. Any conventional method for the cross coupling of an aryl iodide or aryl bromide with an aryl boronic acid or aryl stannane can be employed. In accordance with the preferred embodiment of this invention, the aryl iodide or aryl bromide of formula VII is treated with an appropriately substituted aryl boronic acid, a base, i.e. sodium carbonate or potassium phosphate, and catalytic tetrakis(tripheny!phosphine)palladium (0) or [1,4-bis-(diphenylphosphine) butane]palladium (II) dichloride. This reaction is performed in a high boiling point solvent such as N, N-dimethylformamide, 1,4-dioxane, or 1,2-dimethoxyethane in the presence of water, under nitrogen, at elevated temperatures from 70eC to about 100°C being preferred. Compounds of formula VIII can be formed from compounds -40- WO 2005/037279 PCT/US2004/033732 of formula XII, via the reductive amination or alkylation procedure outlined in either Scheme 2 or Scheme 3. where B is alkenyl or alkynyl. [0114] If it is desired to produce compounds of formula XIV, where B = alkynyl or alkenyl, they can be formed from compounds of formula VII, where R1 = bromine or iodine and where Y = P (see Scheme 1). Compounds of formula XIII can be formed from compounds of formula VII where R1 = bromine or iodine via a cross-coupling reaction with either an appropriately substituted alkenyl or alkynyl stannane. Any conventional method for the cross coupling of an aryl iodide or aryl bromide with an alkenyl or alkynyl stannane can be employed. In accordance with the preferred embodiment of this invention, the aryl iodide or aryl bromide of formula VII is treated with an appropriately substituted alkenyl or alkynyl stannane and catalytic te1rakis(triphenylphosphine)palladium (0). This reaction is performed in high boiling point solvents such as N, N-dimethylformamide or toluene, under nitrogen, at elevated temperatures from 900C to about 1200C being preferred. Compounds of formula XIV are formed from compounds of formula XIV as described in Scheme 1. Compounds of formula VIII can be formed from compounds of formula XIV, via the reductive amination or alkylation procedure outlined in either Scheme 2 or Scheme 3. -41- WO 2005/037279 PCT/US2OO4/O33732 [0115] The compounds of formula I have an asymmetric carbon atom. The preferred stereoconfiguration is S. If it is desired to produce the R or the S isomer of the compounds of formula I, these compounds can be isolated as the desired isomer by any conventional method. Among the preferred means is to separate the isomers of either the amide of formula VI or the amide of formula VII where Y = P or the amine of formula I via either High Performance Liquid Chromatography (HPLC) or via Supercritical Fluid Chromatography. [0116] The separation of R and S isomers can also be achieved by forming a lower alky) ester of phenylacetic acids of formula V. Any conventional method for the formation of an ester from a carboxylic acid can be utilized. Separation is performed using an enzymatic ester hydrolysis of any lower alkyl esters corresponding to the compound of formula IV (See, (or example, Ahmar, M.; Girard, C; Bloch, R. Tetrahedron Lett., 1989, 7053), which results in the formation of corresponding chiral acid and chiral ester. The ester and the acid can be separated by any conventional method of separating an acid from an ester. [0117] In other embodiments, the invention is directed to pharmaceutical compositions, comprising: a. at least compound of formula I or pharmaceutically acceptable salt thereof; and b. at least one pharmaceutically acceptable carrier. Generally, the compound of formula I or a pharmaceutically acceptable salt thereof will be present at a level of from about 0.1%, by weight, to about 90% by weight, based on the total weight of the pharmaceutical composition, based on the total weight of the pharmaceutical composition. Preferably, the compound of formula I or a pharmaceutically acceptable salt thereof will be present at a level of at least about 1%, by weight, based on the total weight of the pharmaceutical composition. More preferably, the compound of formula I or a pharmaceutically acceptable salt thereof will be present at a level of at least about 5%, by weight, based on the total weight of the pharmaceutical composition. Even more preferably, the norepinephrine reuptake inhibitor or a pharmaceutically acceptable salt thereof will be present at a -42- WO 2005/037279 PCT/US2004/033732 level of a\ least about 10%, by weight, based on the total weight of the pharmaceutical composition. Yet even more preferably, the compound of formula I or a pharmaceutically acceptable salt thereof will be present at a level of at least about 25%, by weight, based on the total weight of the pharmaceutical composition. [0118] Such compositions are prepared in accordance with acceptable pharmaceutical procedures, such as described in Remington's Pharmaceutical Sciences, 17th edition, ed. Alfonoso R. Gennaro, Mack Publishing Company, Easton, PA 0985). Pharmaceutically acceptable carriers are those that are compatible with the other ingredients in the formulation and biologically acceptable. [0119] The compounds of this invention may be administered orally or parenterally, neat or in combination with conventional pharmaceutical carriers. Applicable solid carriers can include one or more substances that may also act as flaylring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet-disintegrating agents or an encapsulating material. In powders, the carrier is a finely divided solid that is in admixture with the finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain up to 99% of the active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins. [0120] Liquid carriers may be used in preparing solutions, suspensions, emulsions, syrups, and elixirs. The active ingredient of this invention can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fat. The liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flaylring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers, or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral -43- WO 2005/0J7279 PCT/US2O04/033732 administration include water (particularly containing additives as above, e.g. cellulose- derivatives, preferably sodium carboxymethyl cellulose solution), alcohols including monohydric alcohols and polyhydric alcohols, e.g. glycols) and their derivatives, and oils (e.g. fractionated coconut oil and arachis oil). For parenteral administration the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration. [0121] Liquid pharmaceutical compositions, which are sterile solutions or suspensions, can be administered by, for example, intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously. Oral administration may be either liquid or solid composition form. [0122] Preferably the pharmaceutical composilion is in unit dosage form, e.g. as tablets, capsules, powders, solutions, suspensions, emulsions, granules, or suppositories. In such form, the composition is sub-divided in unit dose containing appropriate quantities of the active ingredient; the unit dosage forms can be packaged compositions, for example packeted powders, vials, ampoules, prefilled syringes or sachets containing liquids. The unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form. [0123] In another embodiment of the present invention, the compounds useful in the present invention may be administered to a mammal with one or more other pharmaceutical active agents such as those agents being used to treat any other medical condition present in the mammal. Examples of such pharmaceutical active agents include pain relieving agents, anti-angiogenic agents, anti-neoplastic agents, anti-diabetic agents, anti-infective agents, or gastrointestinal agents, or combinations thereof. [0124] The one or more other pharmaceutical active agents may be administered in a therapeutically effective amount simultaneously (such as individually at the same time, or together in a pharmaceutical composition), and/or successively with -44- WO 2005/037279 PCT/US2004/033732 one or more compounds of the present invention. [0125] The term "combination therapy" refers to the administration of two or more therapeutic agents or compounds to treat a therapeutic condition or disorder described in the present disclosure, for example hot flush, sweating, thermoregulatory-related condition or disorder, or other. Such administration includes use of each type of therapeutic agent in a concurrent manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein. [0126] The route of administration may be any route, which effectively transports the active compound of formula I to the appropriate or desired site of action, such as oral, nasa!, pulmonary, transderrrial, such as passive or iontophoretic delivery, of parenteral. e.g. rectal, depot, subcutaneous, intravenous, intraurethra!, intramuscular, intranasal, ophthalmic solution or an ointment. Furthermore, the administration of compound of formula I with other active ingredients may be concurrent or simultaneous. [0127] It is believed that the present invention described presents a substantial breakthrough in the field of treatment, alleviation, inhibition, and/or prevention of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nerylus system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof. [0128] Accordingly, in one embodiment, the present invention is directed to methods for treating or preventing a condition ameliorated by monoamine reuptake in a subject in need thereof, comprising the step of: administering to said subject an effective amount of a compound of formula I or pharmaceutically acceptable salt thereof. -45- WO 2005/037279 PCT/US2004/fl33732 The conditions ameliorated by monoamine reuptake include those selected from the group consisting of vasomotor symptoms, sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nerylus system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof. [0129] "Vasomotor symptoms," "vasomotor instability symptoms" and "vasomotor disturbances" include, but are not limited to, hot flushes (flashes), insomnia, sleep disturbances, mood disorders, irritability, excessive perspiration, night sweats, fatigue, and the like, caused by, inter alia, thermoregulatory dysfunction. [0130] The term "hot flush" is an arl-recognized term that refers to an episodic disturbance in body temperature typically consisting of a sudden skin flushing, usually accompanied by perspiration in a subject. [0131] The term "sexual dysfunction" includes, but is not limited to, condition relating to desire and/or arousal. [0132] As used herein, "gastrointestinal and genitourinary disorders" includes irritable bowel syndrome, symptomatic GERD, hypersensitive esophagus, nonulcer dyspepsia, noncardiac chest pain, biliary dyskinesia, sphincter of Oddi dysfunction, incontinence (i.e., urge incontinence, stress incontinence, genuine stress incontinence, and mixed incontinence)(including the inyl]untary yliding of feces or urine, and dribbling or leakage or feces or urine which may be due to one or more causes including but not limited to pathology altering sphincter control, loss of cognitive function, overdistention of the bladder, hyperreflexia and/or inyl]untary urethral relaxation, weakness of the muscles associated with the bladder or neurologic abnormalities), interstitial cystitis (irritable bladder), and chronic pelvic pain (including, but not limited to vulyldynia, prostatodynia, and proctalgia). -46- WO 2005/037279 PCT/US 2004/033 73 2 [0133] As used herein, "chronic fatigue syndrome" (CFS) is a condition characterized by physiological symptoms selected from weakness, muscle aches and pains, excessive sleep, malaise, fever, sore throat, tender lymph nodes, impaired memory and/or mental concentration, insomnia, disordered sleep, localized tenderness, diffuse pain and fatigue, and combinations thereof. [0134] As used herein, "fibromyalgia syndrome" (FMS) includes FMS and other somatoform disorders, including FMS associated with depression, somatization disorder, conversion disorder, pain disorder, hypochondriasis, body dysmorphic disorder, undifferentiated somatoform disorder, and somatoform NOS. FMS and other somatoform disorders are accompanied by physiological symptoms selected from a generalized heightened perception of sensory stimuli, abnormalities in pain perception in the form of allodynia (pain with innocuous stimulation), abnormalities in pain perception in the form of hyperalgesia (increased sensitivity to painful stimuli), and combinations thereof. [0135] As used herein, "nerylus system disorders," includes addictive disorders (including those due to alcohol, nicotine, and other psychoactive substances) and withdrawal syndrome, age-associated learning and mental disorders (including Alzheimer's disease), anorexia nerylsa, bulimia nerylsa, attention-deficit disorder with or without hyperactivity disorder bipolar disorder, pain (including chronic pain selected from the group consisting of lower back pain, atypical chest pain, headache such as cluster headache, migraine, herpes neuralgia, phantom limb pain, pelvic pain, myofascial face pain, abdominal pain, neck pain, central pain, dental pain, opioid resistant pain, visceral pain, surgical pain, bone injury pain, pain during labor and delivery, pain resulting from burns, post partum pain, angina pain, neuropathic pain such as peripheral neuropathy and diabetic neuropathy, post-operative pain, and pain which is co-morbid with nerylus system disorders described herein), cyclothymic disorder, depression disorder (including major depressive disorder, refractory depression adolescent depression and minor depression), dysthymic disorder, generalized anxiety disorder (GAD), obesity {i.e., reducing the weight of obese or overweight patients), obsessive compulsive disorders and related spectrum disorders, oppositional defiant disorder, panic disorder, post-traumatic stress -47- WO 2005/037279 PCT/US2004/033732 disorder, premenstrual dysphoric disorder (i.e., premenstrual syndrome and late luteal phase dysphoric disorder), psychotic disorders (including schizophrenia, schizoaffective and schizophreniform disorders), seasonal affective disorder, sleep disorders (such as narcolepsy and enuresis), social phobia (including social anxiety disorder), selective serotonin reuptake inhibition (SSRI) "poop out" syndrome (i.e., wherein a patient who fails to maintain a satisfactory response to SSRI therapy after an initial period of satisfactory response). [0136] In one embodiment, the present invention is directed to methods for treating or preventing vasomotor symptoms in a subject in need thereof, comprising the step of: administering to said subject an effective amount of at least one compound of formula I or pharmaceutically acceptable salt thereof. [0137] When estrogen levels are low or estrogen is absent, the normal levels between NE and 5-HT is altered and this altered change in neurotransmitter levels may result in changes in the sensitivity of the thermoregulatory center. The altered chemical levels may be translated in the thermoregulatory center as heat sensation and as a response, the hypothalamus may activate the descending autonomic pathways and result in heat dissipation via vasodilation and sweating (hot flush) (Figure 1). Accordingly, the estrogen deprivation may result in altered norepinephrine activity. [0138] Norepinephrine synthesized in perikarya of the brainstem is released at the nerve terminals in the hypothalamus and brainstem. In the hypothalamus, NE regulates the activity of neurons residing in the thermoregulatory center. In the brainstem, NE innervates serotoninergic neurons (5HT), and acting via adrenergic#a1 and adrenergic#a2 postsynaptic receptors, it stimulates the activity of the serotoninergic system. In response, 5-HT neurons also modulate the activity the thermoregulatory center and feedback to NE neurons. Via this feedback connection, 5-HT, acting via 5-HT2a receptors, inhibit the activity of NE neurons. Norepinephrine in the synaptic cleft is also taken up by NE transporter (NET) located in NE neurons. The transporter recycles NE and makes it available for multiple neurotransmission -48- WO 2005/037279 PCT/US2004/033732 (Figure 2). [0139] The present invention provides a treatment for vasomotor symptoms by methods of recovering the reduced activity of norepinephrine. Norepinephrine activity in the hypothalamus or in the brainstem can be elevated by (i) blocking the activity of the NE transporter, (ii) blocking the activity of the presynaptic adrenergic C2 receptor with an antagonist, or (iii) blocking the activity of 5-HT on NE neurons with a 5-HT2a antagonist. [0140] In another embodiment, the present invention is directed to methods for treating or preventing a depression disorder in a subject in need thereof, comprising the step of: administerring to said subject an effactive amount of at least one compound of formula I or pharmaceutically acceptable salt thereof. [0141] In yet other embodiments, the present invention is directed to methods for treating or preventing sexual dysfunction in a subject in need thereof, comprising the step of: administering to said subject an effective amount of at least one compound of formula I or pharmaceutically acceptable salt thereof. [0142] In another embodiment, the present invention is directed to methods for treating or preventing gastrointestinal or genitourinary disorder, particularly stress incontinence or urge urinary incontinence, in a subject in need thereof, comprising the step of: administering to said subject an effective amount of a compound of formula I or pharmaceutically acceptable salt thereof. [0143] In another embodiment, the present invention is directed to methods for treating or preventing chronic fatigue syndrome in a subject in need thereof, comprising the step of: administering to said subject an effective amount of a compound of formula I or pharmaceutically acceptable salt thereof. -49- WO 2005/037279 PCT/US2O04/033732 [0144]-In another embodiment, the present invention is directed to methods for treating or preventing fibromylagia syndrome in a subject in need thereof, comprising the step of: administering to said subject an effective amount of a compound of formula I or pharmaceutically acceptable salt thereof. [0145] In further embodiments, the present invention is directed to methods for treating or preventing pain in a subject in need thereof, comprising the step of: administering to said subject an effective amount of at least one compound of formula I or pharmaceutically acceptable salt thereof. [0146] The pain may be, for example, acute pain (short duration) or chronic pain (regu!ariy reoccurring or persistent). The pain may also be centralized or peripheral. [0147] Examples of pain that can be acute or chronic and that can be treated in accordance with the methods of the present invention include inflammatory pain, musculoskeletal pain, bony pain, lumbosacral pain, neck or upper back pain, visceral pain, somatic pain, neuropathic pain, cancer pain, pain caused by injury or surgery such as burn pain or dental pain, or headaches such as migraines or tension headaches, or combinations of these pains. One skilled in the art will recognize that these pains may overlap one another. For example, a pain caused by inflammation may also be visceral or musculoskeletal in nature. [0148] In a preferred embodiment of the present invention the compounds useful in the present invention are administered in mammals to treat chronic pain such as neuropathic pain associated for example with damage to or pathological changes in the peripheral or central nerylus systems; cancer pain; visceral pain associated with for example the abdominal, pelvic, and/or perineal regions or pancreatitis; musculoskeletal pain associated with for example the lower or upper back, spine, fibromylagia, temporomandibular joint, or myofascial pain syndrome; bony pain associated with for example bone or joint degenerating disorders such as osteoarthritis, rheumatoid arthritis, or spinal stenosis; headaches such migraine or -50- WO 2005/037279 PCT/US2004/033732 tension headaches; or pain associated with infections such as HIV, sickle cell anemia autoimmune disorders, multiple sclerosis, or inflammation such as osteoarthritis or rheumatoid arthritis. [0149] In a more preferred embodiment, the compounds useful in this invention are used to treat chronic pain that is neuropathic pain, visceral pain, musculoskeletal pain, bony pain, cancer pain or inflammatory pain or combinations thereof, in accordance with the methods described herein. Inflammatory pain can be associated with a variety of medical conditions such as osteoarthritis, rheumatoid arthritis, surgery, or injury. Neuropathic pain may be associated with for example diabetic neuropathy, peripheral neuropathy, post-herpetic neuralgia, trigeminal neuralgia, lumbar or cervical radiculopathies, fibromyalgia, glossopharyngeal neuraigia, refiex sympaiheiic dysirophy, casuaiyla, ihaiarnic syndrome, nerve rooi avulsion or nerve damage cause by injury resulting in peripheral and/or centra! sensitization such as phantom limb pain, reflex sympathetic dystrophy or posrthoracotomy pain, cancer, chemical injury, toxins, nutritional deficiencies, or viral or bacterial infections such as shingles or HIV, or combinations thereof. The methods of use for compounds of this invention further include treatments in which the neuropathic pain is a condition secondary to metastatic infiltration, adiposis dolorosa, burns, or central pain conditions related to thalamic conditions. [0150] As mentioned previously, the methods of the present invention may be used to treat pain that is somatic and/or visceral in nature. For example, somatic pain that can be treated in accordance with the methods of the present invention include pains associated with structural or soft tissue injury experienced during surgery, dental procedures, burns, or traumatic body injuries. Examples of visceral pain that can be treated in accordance with the methods of the present invention include those types of pain associated with or resulting from maladies of the internal organs such as ulcerative colitis, irritable bowel syndrome, irritable bladder, Crohn's disease, rheumatologic (arthralgias), tumors, gastritis, pancreatitis, infections of the organs, or biliary tract disorders, or combinations thereof. One skilled in the art will also recognize that the pain treated according to the methods of the present invention may also be related to conditions of hyperalgesia, allodynia, or both. -51- WO 2005/037279 PCT/US2004/033732 Additionally, the chronic pain may be with or without peripheral or central sensitization. [0151] The compounds useful in this invention may also be used to treat acute and/or chronic pains associated with female conditions, which may also be referred to as female-specific pain. Such groups of pain include those that are encountered solely or predominately by females, including pain associated with menstruation, ovulation, pregnancy or childbirth, miscarriage, ectopic pregnancy, retrograde menstruation, rupture of a follicular or corpus luteum cyst, irritation of the pelvic viscera, uterine fibroids, adenomyosis, endometriosis, infection and inflammation, pelvic organ ischemia, obstruction, intra-abdominal adhesions, anatomic distortion of the pelvic viscera, ovarian abscess, loss of pelvic support, tumors, pelvic congestion or referred pain from non-gynecological causes. EXAMPLES i [0152] The present invention is further defined in the following Examples, in which all parts and percentages are by weight and degrees are Celsius, unless otherwise stated. It should be understood that these examples, while indicating preferred embodiments of the invention, are given by way of illustration only. From the above discussion and these examples, one skilled in the art can ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Reference Example 1-a: Aldol Reaction: Preparation of Acid Intermediates [0153] A solution of diisopropylamine (7.87 mL, 56.2 mmol) in dry tetrahydrofuran (50 mL) under nitrogen was cooled to -78 °C and treated dropwise with a solution of n-butyl]ithium (2.5 M in hexanes, 22 mL, 55.0 mmol). The resulting solution was warmed to 0 °C and stirred for 15 min. The solution was re-cooled to -78 °C and treated, via cannula, with a solution of 3-chlorophenylacetic acid (4.0 g, 23.4 mmol) in -52- W0 2005/037279 PCT/US2O04/033732 tetrahydrofuran (20 ml). The reaction was then allowed to warm to 25 X where it was stirred, for 45 minutes and was then re-cooled to -78 X. A solution of cyclohexanone (3.65 ml, 35.3 ml) in tetrahydrofuran 00 ml) was then added via cannula, and the resulting mixture was stirred at -78 X for 1.5 h. The reaction was then quenched by the addition of a saturated aqueous solution of ammonium chloride, and the tetrahydrofuran was removed in vacuo. The resulting residue was dissolved in a 2N aqueous solution of sodium hydroxide (30 mL) and washed with ethyl acetate 0 x 30 mL). The aqueous layer was then acidified to pH = 1 with the addition of a 2 N aqueous solution of hydrochloric acid. The product was extracted with ethyl acetate (3 x 30 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated in vacuo to yleld 6.05 g (96%) of pure (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid as a white solid. HRMS: calcd for C14H17CIO3, 268.0866; found (ES!_FT), 231.0743. b) In an analogous manner, (3-bromophenyl)(1-hydroxycyclohexylacetic acid was prepared from 3-bromophenylacetic acid and cyclohexanone. HRMS: calcd for C14H17Br03, 312.0361; found (ESI_FT), 350.99924. c) In an analogous manner, 0 -hydroxycyclobutyl)(2-naphthyl)acetic acid was prepared from 2-napthylacetic acid and cyclobutanone. HRMS: calcd for C16H16O3, 256.1099; found (ESI_FT), 279.09927. d) In an analogous manner, 3.4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacetic acid was prepared from 3, 4-dichlorophenylacetic acid and cyclohexanone. MS (ESI) m/z 301/303/305 ([M-H]); Anal. Calcd for C14H16CI2O3: C, 55.46; H, 5.32; N, 0.00. Found: C, 55.42; H, 5.30; N, 0.00. e) In an analogous manner, (1-hydroxycyclohexy)(1-naphthyl)acetic acid was prepared from 1-napthylacetic acid and cyclohexanone. MS (ESI) m/z 283 ([M- H]); HRMS: calcd for C18H2o03, 284.1412; found (ESI_FT), 307.13001. f) In an analogous manner, 0-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid was prepared from 3-trifluoromethoxyphenylacetic acid and cyclohexanone. HRMS: calcd for C15H17[3O4, 318.1079; found (ESI), 317.1013. g) In an analogous manner, (1-hydroxycyclohexyl)[4-(trifluoromethoxy)phenyl]acetic acid was prepared from 4-trifluoromethoxyphenylacetic acid and cyclohexanone. MS (ESI) m/z 317 ([M-H]+). -53- WO 2005/037279 PCT/US200-I/033732 h) In an analogous manner, (4-bromophenyl)0 -hydroxycyclohexyl)acetic acid was prepared from 4-bromophenylacetic acid and cyclohexanone. MS (ESI) m/z 313/315 ((M+H]4); Anal. Calcd for CKH17BrO3: C, 53.69; H, 5.47; N, 0.00. Found: C, 53.87; H, 5.42; N, 0.00. i) In an analogous manner, (3.4-dichlorophenyl)(4-hydroxy-1 -methylpiperidin-4-yl)acetic acid was prepared from 3,4-dichlorophenylacetic acid and 1-methyl-4-piperidone. HRMS: calcd for C14H17CI2NO3 HCI, 353.0352; found (ESI_FT), 318.0653. j) In an analogous manner, (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid was prepared from 3-bromophenylacetic acid and cyclobutanone. HRMS: calcd for Cl2H13BrO3, 284.0048; found (ESI_FT), 306.99337. k) In an analogous manner, 0-hydroxycyclobuty0[3-(trifluorornethoxv)phenyl]acetic acid was prepared from 3-trifluoromethoxyphenylacetic acid and cyclobutanone. HRMS: calcd for C3H13[3O4, 290.0766; found (ESI), 289.0686. I) In an analogous manner, (3-bromo-4-methoxyphenyl)(1-hydroxycyclohexyl)acetic acid was prepared from 3-bromo-4-methoxyphenylacetic acid and cyclohexanone. MS (ESI) m/z 341/343 ([M-H]+); HRMS: calcd for C15H13BrO4, 342.0467; found (ESI_FT), 341.03897. m) In an analogous manner, (1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetic acid was prepared from 3-trifluoromethylphenylacetic acid and cyclohexanone. MS (ESI) m/z 301 ([M-H]+); HRMS: calcd for C15H17[3O3, 302.1130; found (ESLFT), 325.1024. n) In an analogous manner, (4-Benzyloxyphenyl)(1-hydroxycyclohexyl)acetic acid was prepared from 4-benzyloxyphenylacetic acid and cyclohexanone. o) In an analogous manner, (1-hydroxycyclobutyl)(1 -naphthyl)acetic acid was prepared from 1-napthylacetic acid and cyclobutanone. p) In an analogous manner, (3.4-dichlorophenyl)(1-hydroxycyclobutyl)acetic acid was prepared from 3, 4-dichlorophenylacetic acid and cyclobutanone. HRMS: calcd for C12H12CI2O3, 274.0163; found (ESI_FT), 273.00881. q) In an analogous manner, (1-hydroxycyclohexyl)(2-naphthyl)acetic acid was prepared from 2-napthylacetic acid and cyclohexanone. HRMS: calcd for C18H20O3, 284.1412; found (ESI_FT), 323.10414. -54- WO 2005/037279 PCT/US2004/033732 r) In an analogous manner, (3-bromophcnyl)(4-hydroxv-1-methylpiperidin-4-.yl)acetic acid was prepared from 3-bromophenylac.etic acid and 1-methyl-.4-piperidone. HRMS: calcd for C14H18BrNO3 HCI 363.0237; found (ESI_FT), 328.05356. s) In an analogous manner, (1-hydroxycyclopentyl)0 -naphthy)acotic acid was prepared from 1-napthylacefic acid and cyclopentanone. MS (ESI) m/z 269 ([M-H]); HRMS: calcd forC17H18O3, 270.1256; found (ESI_FT), 293.11485. t) In an analogous manner, 2-(3-bromophenyl)-3-ethyl-3-hydroxypentanoic acid was prepared from 3-bromophenylacetic acid and 3-pentanone. MS (ESI) m/z 299/301 ([M-H]+); HRMS: calcd for C13H17BrO3, 300.0361; found (ESLFT), 323.02505. u) In an analogous manner, 2-(3-chlorophenyl)-3-hydroxy-3-propylhexanoic acid was prepared from 3-bromophenylacetic acid and 4-heptanone. MS (ESI) m/z 283/285 ([M1H]+) HRMS: calcd for C15H21ClO3 284.1173; found (ES!_FT), 307.1074. v) In an analogous manner, 2-(3-chlorophenyl)-3-ethyl-3-hydroxypentanoic acid was prepared from 3-chlorophenylacetic acid and 3-pentanone. MS (ESI) m/z 255/257 ([M+H]+). w) In an analogous manner, 3-ethyl-3-hydroxy-2-(1 -naphthyl)pontanoic acid was prepared from 1-napthylacetic acid and 3-pentanone. MS (ESI) m/z 271 ([M-H]'). x) In an analogous manner, (4-hydroxv-1-methylpiperidin-4-yl)(2-naphthyl)acetic acid was prepared from 2-napthylacetic acid and 1-methyl-4-piperidone. HRMS: calcd for C18H21NO3, 299.1521; found (ESI_FT), 300.15911. y) In an analogous manner, 2-(3-bromo-4-methoxyphenyl)-3-ethyl-3-hydroxypentanoic acid was prepared from 3-bromo-4-methoxypheny!acetic acid - and 3-pentanone. MS (ESI) m/z329/331 ([M+H]+). z) In an analogous manner, (4-Benzyloxyphenyl)(1-hydroxycyclobuty)acetic acid was prepared from 4-benzyloxyphenylacetic acid and cyclobutanone. aa) In an analogous manner, (3-chlorophenyl)0-hydroxydecahydronapthyl]acetic acid was prepared from 3-chlorophenylacetic acid and decahydronapthlene-1-one. MS (ESI) m/z 321/323 ([M-H]+). bb) In an analogous manner, (3-bromo-4-methoxyphenyl)(4-tert-butyl-1-hydroxycyclohexyl)acetic acid was prepared from 3-bromo-4- -55- WO 2005/037279 PCT/US2004/033732 methoxyphenylacetic acid and 4- tert-butylcyclohexanone. MS (ESI) m/z 397/399 [M-H]); HRMS: calcd for C19H27BrO4 398.1093; found (ESI_FT), 421.09875. cc) In an analogous manner, (3-chlorophenyl)(2-hydroxyl)ecahydronapthyl)acetic aci_d was prepared from 3-chlorophenylacetic acid and decahydronapthlene-2-one. MS (ESI) m/z321/323 ([M-H]+). dd) In an analogous manner, (4-tet-butyl-1-hydroxycyclohexyl)(1-naphthyl)acetic acid was prepared from 1-napthylacetic acid and 4- tert-butylcyclohexanone. MS (ESI) m/z 339 ([M-H]); HRMS: calcd for C22H28O3, 340.2038; found (ESI_FT), 363.19309. ee) In an analogous manner, (3-chlorophenyl)(4-hydroxytetrahydro-2H-pvran-4-yl)acetic acid was prepared from 3-chlorophenylacetic acid and tetrahydro-2H-pyran-4-one. MS (ESI) m/z 269 ([M-H]+); HRMS: calcd for C13H15CIO4, 270.0659; found (ESLFT), 293.05499. ff) in an analogous manner, ('3-bromophenyl)(4-fe/t-butyl-1-hydroxvcyclohexyl)acetic acid was prepared from 3-bromophenylacetic acid and 4- tert-butylcyclohexanone. MS (ESI) m/z 367/369 ([M-H]'); HRMS: calcd for C18H25Br03. 368.0987; found (ESI_FT), 391.0878. gg) In an analogous manner, 2-(3-bromophenyl)-3-hydroxy-3-propylhexanoic acid was prepared from 3-bromophenylacetic acid and 4-heptanone. MS (ESI) m/z 327/329 ([M+H]+). hh) In an analogous manner, 2-(3-chlorophenyl-3.3-dicyclopropyl-3-hydroxypropanoic acid was prepared from 3-chlorophenylacetic acid and dicyclopropyl ketone. MS (ESI) m/z 279.0801 ([M-H]'); HRMS: calcd for C15H17CIO3, 280.0866; found (ESI), 279.0801; Anal. Calcd for C15H17CIO3: C, 64.17; H, 6.10; N, 0.00. Found: C, 64.05; H, 6.31; N, 0.00. ii) In an analogous. manner, (3-bromophenyl)0-hydroxv-3,3,5,5-tetramethylcyclohexyl)acetic acid was prepared from 3-bromophenylacetic acid and 3,3,5,5-tetramethylcyclohexanone. MS (ESI) m/z367/369 ([M-H]'). jj) In an analogous manner, (4-ethyl-1-hydroxycyclohexyl) -(1-naphthyl) acetic acid was prepared from 1-napthylacetic acid and 4-ethylcyclohexanone. MS (ESI) m/z 311 ([M-H]). -56- W'O 2005/037279 PCT/US2004/033732 kk) In an analogous manner, (3-chorophnyl)(4-tert-buty[-1-hydroxycyclohexyl)acetic acid was prepared from 3-chlorophenylacetic acid and 4- tert-butylcyclohexanone. II) In an analogous manner, (4-methyl-1-hydroxycyclohexyl) -(1-naphthyl) acetic acid was prepared from 1-napthylacetic acid and 4-methylcyclohexanone. MS (ESI) m/z 297 ([M-H]). mm) In an analogous manner, (3-bromophenyl)(4-hydroxyletrahydro-2H-pyran-4- yl)acetic acid was prepared from 3-bromophenylacetic acid and tetrahydro-2H- pyran-4-one. MS (ESI) m/z 313/315 ([M+H]+); HRMS: calcd for Cl3H15BrO4 314.0154; found (ESI..FT), 315.02244. nn) In an analogous manner, (3-Benzyloxyphenyl)(1-hydroxycyclohexyl)acetic acid was prepared from 3-benzyloxyphenylacetic acid and cyclohexanone. oo) In an analogous manner, (3-brcrriophenyl)(2-hydroxy-2-adamantyl)acetic acid was prepared from 3-bromophenylacetic acid and adamantanone. MS (ESI) m/z 363/365 ([M-H]+). pp) In an analogous manner, (3-bromo-4-methoxyphenyl)(4-hydroxytetrahydro-2H- pvran-4-yl)acetic acid was prepared from 3-bromo-4-methoxyphenylacetic acid and tetrahydro-2H-pyran-4-one. MS (ESI) m/z343/345 ([M-H]+); HRMS: calcd for C14H17BrO5, 344.0259; found (ESI_FT), 367.01582. qq) In an analogous manner, (3-benzyloxyphenylH1 -hydroxycyclobutyl)acetic acid was prepared from 3-benzyloxyphenylacetic acid and cyclobutanone. rr) In an analogous manner,(5-chlorothien-2-yl)(1-hydroxycyclohexyl)acetic acid was prepared from 5-chloro-2-thiophene-3-acetic acid (Example 142) and cyclohexanone. MS (ESI) m/z 273/275 ([M-H]-). ss) In an analogous manner, (5-bromothien-2-yl)0 -hydroxycyclohexyl)acetic acid was prepared from 5-bromo-2-thiophene acetic acid (Example 143) and cyclohexanone. MS (ESI) m/z 317/319 ([M+H]+) tt) In an analogous manner; 1 -benzothien-3-yl(1-hydroxycyclohexyl)acetic acid was prepared from 1-benzothien-3-yl acetic acid and cyclohexanol. MS (ESI) m/z 289 ([M-H]-) uu) In an analogous manner. (2-bromophenyl)0-hydroxycyclohexyl)acetic acid was prepared from 2-bromophenylacetic acid and cyclohexanol. MS (ESI) m/z 311/313 ([M-H]-) -57- WO 2005/037279 PCT/US2004/033732 vv) In an analogous manner, (4-bromophGnyl)0-hydroxycyclohexyl)acetic acid was prepared from 4-bromophenylacetic acid and cyclohexanone. MS (ESI) m/z 313/315 ([M+H]+); Anal. Calcd for C14H17Br03 C, 53.69; H, 5.47; N, 0.00. Found: C, 53.87; H, 5.42; N, 0.00. ww) In an analogous manner, (4-bromophenyl)(1-hydroxycyclobuty)acetic acid was prepared from 4-bromophenylacetic acid and cyclobutanone. xx) In an analogous manner, (1-methyl-1H-indol-3-yl) 0-hydroxvcylclohexyl) acetic acid was prepared from N-Methyl-3-indole acetic acid and cyclohexanone. yy) In an analogous manner, (1-(tert-butyl-dimethyl-silanyl)-1H-indol-3-yl) 0- hydroxycylclohexyl) acetic acid was prepared from [i-(tert-butyl-dimethyl-silanyl)- 1H-indol-3-yl]-acetic acid1 and cyclohexanone. zz) In an analogous manner, (1-hydroxycyclohexyl)0.1'-biphenyl-4-yl)acetic acid was prepared from 4-biphenylacetic acid and cyclohexanone. MS (ESI) m/z 309 ([M- H]-) aaa) In an analogous mannerd -hyl)oxvcyclobutyl)[4-trifluoromethoxy)phenyn acetic acid was prepared from 4-trifluoromethoxyphenyl acetic acid and cyclobutanone. MS (ESI) m/z 289 ([M-H]'). bbb) In an analogous manner 0-hyl)oxvcyclohexyl)[4-phenoxyphenyl] acetic acid was prepared from 4-phenoxyphenylacetic acid and cyclohexanone. MS (ESI) m/z 325 ([M-H]-). ccc) In an analogous manner 0-hydoxycyclohexy)[3-phenoxyphenyl] acetic acid was prepared from 3-phenoxyphenylacetic acid and cyclohexanone. MS (ESI) m/z 325 ([M-H]+). Anal. Calcd for C2oH22040.1 H2O: C.73.19; H, 6.82. Found: C, 73.04; H, 6.88. ddd) In an analogous manner, (1-naphthyl)(1-hydroxycyclooctyl)acetic acid was prepared from 1-naphthyl acetic acid acid and cyclooctanone. eee) In an analogous manner, [4-(Benzyloxy)-3-chlorophenyl](1- hydroxycyclohexyl)acetic acid was prepared from [4-(benzyloxy)-3- chlorophenyl]acetic acid (DE 2556474, 1976, M.Kucher; B.Brunova; J. Grimova; N. Oldrich) and cyclohexanone. MS (ESI) m/z 373; ' Sclidphase synthesis o? polyanyl]e spider toxins and correlation with the natural products by HPLC-MS/MS. Manov, Nkolay; Tzouros, Manuc!; Chesnov, Sergiy; Bigleo Laurent; Bienz, Slcfan. Institute of Organic Chemistry, University of Zurich, Zurich, Sw!t2. Helvetica Ch:mica AOB (2032)," 85(9), 2827-2816 -58- WO 2005/037279 PCT/US2004/033732 fff) In an analogous manner, (1 -naphthyl)(1-hydroxvcycloheptyl)acetic acid was prepared from 1-napthylacetic acid and cycloheptanone. ggg) In an analogous manner, 2-(3-chlorophonyl)-3-hydroxy-3-methylbutanoic acid was prepared from 3-chlorophenylacetic acid and acetone. MS (ES) m/z 226.9. hhh) In an analogous manner, (3-chlorophenyl)0-hydroxy-3.3.5.5-tetramethylcyclohexyl)acetic acid was prepared from 3-chlorophenylacetic acid and 3,3,5,5-tetramethylcyclohexanone. MS (ES) m/z 323.2. iii) In an analogous manner, (1-hydroxy-cyclohexyl)-(5-methoxy-benzo[b]thiophen-3-yl)-acetic acid was prepared from 5-methoxy benzo[b]thiophene acetic acid (Campaigne, E.; Kim, C.S.; Pinza, M.; Pifferi, G. J. Heterocyclic Chem. 1983, 20, 1697-1703) and cyclohexanone. HRMS: calcd for C15H17[3O4, 318.1079; found (ESI), 317.1013. jjj) in an analogous manner, (2-hydroxydecahydronapthy!)0-napthyl)acetic acid was prepared from 1-napthy!acetic acid and decahydronaptblene-2-one. MS (ESI) m/z337 {[MM]). kkk) In an analogous manner, (3-chlorophenyl)(4-methyl-1 -hydroxycyclohexyl) acetic acid was prepared from 3-chlorophenylacetic acid and 4-methylcyclohexanone. MS (ESI) m/z 281/283 ([M-H]+). Ill) Step 1: A mixture of 4-(ch!oromethyl)dibenzyl (0.92 g, 4 mmol) and potassium cyanide (.039 g, 6 mmol) in N.N-dimethylformamide (20 mL) was heated at 80 °C for 16 hours. At the end of this time the solution was poured into water and extracted 2 times with ethyl acetate. The extracts were combined and filtered through a plug of silica gel. The filtrate was concentrated to yleld 4-(phenethylphenyl)acetonitrile as an oil which was used in the next step without further purification. Step 2: 4-(Phenethylpheny))acetonitrile from the above reaction was treated with a 6 N aqueous solution of-hydrochloric acid 00 mL) and heated at 95 °C for 4 h. The reaction was cooled to 0 °C and solid potassium hydroxide was added until pH 14 was achieved. The solution was washed twice with diethyl ether and the resulting aqueous layer was then acidified to pH 1 with concentrated hydrochloric acid. The product was extracted with diethyl ether (2 X 50 mL) and the combined ethereal extracts were dried over magnesium sulfate and concentrated. -59- WO 2005/03727'J PCT/US2OO4/O33732 Trituration with hexane and fitration of the resulting solid afforded 0.64 g of 4-(2- phenylethyl)phenyl]acetic acid as an off white solid. MS (ESI) m/z 239. Step3: In an analogous manner (as Reference Example l-a), [1-hydroxycyclohexyl)[4-(2-phenylethyl)phenyl]acelic acid was prepared from [4-(2-phenylethyl)phenyl]acetic acid and cyclohexanone. MS (ESI) m/z 337. mmm)Step 1: 3-Fluoro-4-hydroxyphenylacetic acid (0.85 g, 3.62 mmol) and of benzyl bromide 0.30 g, 7.60 mmol) were added to a flask containing N,N'-dimethylformamide (20 mL). Potassium carbonate 0.25 g, 9.00mmol) was then added, and the solution was heated at 50 CC for 4 hours. A 2 N aqueous solution of sodium hydroxide 00 mL) was added and heating was maintained for an additional 16 hours. At the end of this time the solution was poured into water and washed twice with diethyl ether. The ethereal extracts were discarded and the aqueous layer was acidified with concentrated hydrochloric acid until pH 1 was achieved. The product was then extracted with dielhyl ether (2 x 50 mi_). The combined ethereal layers were dried over magnesium sulfate and concentrated to afford 0.95 g of 4-benzyloxy-3-fluorophenylacetic acid which was used as such in the next step. MS (ESI) m/z 325. Step 2: In an analogous manner (as Reference Example l-a), [4-(benzyloxy)-3-fluorophenyl)(1-hydroxycyclohexyl)acetic acid was prepared from [4-(benzyloxy)-3-fluorophenyl]acetic acid and cyclohexanone. MS (ESI) m/z 357. nnn) In an analogous manner, [4-(benzyloxy)-3-methoxyphenyl]0- hydroxycyclohexyl)acetic acid was prepared from [4-(benzyloxy)-3-methoxyphenyl] acetic acid and cyclohexanone. MS (ES) m/z 369.0. ooo) Step 1: In an analogous manner to Reference Example l-mmm, step 1 (3-chloro-4-[(3-methoxybenzyl)oxy]phenyl)acetic acid was prepared from {3-chloro-4-hydroxy-phenyl) acetic acid and 3-methoxybenzyl chloride. Step 2: In an analogous manner (as Reference Example l-a), [3-chloro-4-(3-methoxy-Benzyloxy)-phenyl](1-hydroxy-cyclohexyl)acetic acid was from {3-chloro-4-[(3-methoxybenzyl)oxy]phenyl}acetic acid and cyclohexanone. ppp) Step 1: In an analogous manner \o Reference Example l-mmm, step 1 (3-chloro-4-[(2-methoxybenzyl)oxylphenyl]acetic acid was prepared from {3-chloro-4-hydroxy-phenyl) acetic acid and 2-methoxybenzyl chloride .MS (ES) m/z 304.9. -60- WO 2005/037279 PCT/US2O04/O33732 Step 2: In an analogous manner (as Reference Example l-a), [3-chloro-4-[2-methoxy-benzyloxy)-phenyl]-(1-hydroxy-cyclohexyl)-3cetic acid was from (3-chloro-4-[(2-methoxybenzyl)oxy]phenyl}acetic acid and cyclohexanone. qqq) In an analogous manner, [(3R)-1 -hydroxv-3-methylcyclopentyll[3-(trifluoromethoxy)phenyl]acetic acid was prepared from (3-trifluoromethoxy-phenyl)-acetic acid and 3(R)-methyl-cyclopentanone. rrr) In an analogous manner, (1-hydroxy-2.2-dimethyl-cyclopentyl)-(3-trifluoromethoxy-phenyl)-acetic acid was prepared from (3-trifluoromethoxy-phenyl)-acetic acid and 2,2-dimethyl-cyclopentanone. sss) In an analogous manner, (1-hydroxycyclohexyl)(6-methoxy-2-naphthyl)acetic acid was prepared from (6-methoxy-2-naphthyl)acetic acid (Harrison, Ian Thomas; Lewis, Brian; Nelson, Peter; Rooks, Wendell; Roszkowski, Adolph; Tomolonis, Albert; Fried, John H. J. Med. Chem. 1970, 75, 203-5) and cyciohexanone. MS (ES) m/z 313.0; HRMS: calcd for C13H22O4 + H+, 315.15909; found (ESI, [M+H]+), 315.159. ttt) In an analogous manner, (3-chloro-4-methoxyphenyl)-1 (1-hydroxycyclohexyl) acetic acid was prepared from (3-chloro-4-methoxyphenyl)acetic acid and cyclohexanone. MS(ESI) m/z 297 ([M-H]). uuu) In an analogous manner, (1-hydroxycyclohexyl)-(4- phenethyloxyphenyl) acetic acid was prepared from (4- phenethyloxyphenyl) acetic acid and cyclohexanone. MS(ESI) m/z 353 ([M-H]-). wv) Step 1: In an analogous manner to Reference Example l-mmm, step 1 (4-[2-(4-fluoro-phenyl)-ethoxyl-phenyl)-acetic acid was prepared from (4-hydroxyphenyl)acetic acid and 2-(4-fluorophenyl)ethyl bromide. MS(ESI) m/z 273 ([M-H]-). Step 2: In an analogous manner (as Reference Example l-a), (4-[2-(4-fluoro-phenyl)-ethoxv]-phenyl)-( 1 -hydroxy-cyclohexyl)-acetic acid was prepared from {4-[2-(4-fluoro-phenyl)-ethoxy]-phenyl}-acetic acid and cyclohexanone. MS(ESI) m/z 371 ([M-H]") www) Step 1: In an analogous manner to Reference Example l-mmm, step 1 [4-(2-naphthalen-1 -yl-ethoxy)-phenyl]-acetic acid was prepared from (4-hydroxyphenyl)acetic acid and 1-(2-bromoethyl)napthalene. MS(ESI) m/z 305 ([M-H]-). -61- WO 2005/037279 PCT/DS2004/033732 Step 2: In an analogous manner (as Reference Example l-a), 0-hydroxv-cyclohexyl)-[4-(2-narlhthalen-1 -yl-ethoxy)-phenyl]-acetic acid was prepared from • [4-(2-naphthalen-1-yl-ethoxy)-phenyl]-acetic acid and cyclohexanone. MS(ESI) m/z403 ([M-H]) xxx) Step 1: In an analogous manner to Reference Example l-mmm, step 1 (4-[2-(4-methoxy-phenyl)-ethoxv1-phenyl)-acetic acid was prepared from (4-hydroxyphenyl)acetic acid and 4-(2-chloroethyl)anisole. MS(ESI) m/z 273 ([M-H]' Step 2: In an analogous manner (as Reference Example l-a), 0-hydroxy-cyclohexyl)-(4-[2-(4-methoxy-phenyl)-ethoxyl-phenyl}-acetic acid was prepared from {4-[2-(4-methoxy-phenyl)-ethoxy]-phenyl}-acetic acid and cyclohexanone. MS(ESI)m/z 383 ([M-H]-) yyy) Step 1: In an analogous manner to Reference Example l-mmm, step 1 (4; Cyclohexylmethoxy-phenyl)-acetic acid was prepared from (4-hydroxyphenyl)acetic acid and cyclomethyl bromide. MS(ESI) m/z 247 ([M-H]'). Step 2: In an analogous manner (as Reference Example l-a), {4-cyclohexylmethoxy-pheny)-(1-hydroxy-cyclohexyl)-acetic acid was prepared from (4-cyclohexylmethoxy-phenyl)-acetic acid and cyclohexanone. MS(ESI) m/z 345 ([M-H]) zzz) Step 1: To a stirred solution of (4-hydroxyphenyl)acetic acid methyl ester (0.33 g, 0.002 mole), S-(-)-sec-phenethyl alcohol (0.24 g , 0.002 mole) and triphenylphosphine (0.52 g , 0.002 mole) in anhydrous tetrahydrofuran (6 mL) was added dropwise over 15 minutes diisopropyl azodicarboxylate (0.40 g, 0.002 mole) in tetrahydrofuran 06 mL). The reaction solution was stirred for 1 h at room temperature and was then evaporated to dryness in vacuo. To the residue was added methanol 02 mL) and sodium hydroxide (0.44g, 0.011 mole), and the reaction solution was stirred under reflux for 1 h. The methanol was then removed in vacuo, and to the residue was added 12 mL of water. After stirring for 1 h, the precipitated triphenylphosphine oxide was removed by suction filtration. The aqueous filtrate was extracted with 25 mL of ethyl acetate . The ethyl acetate phase was discarded and the aqueous phase was acidified with concentrated hydrochloric acid giving the solid product 4-( (1R)-1-phenylethoxyphenyl)acetic acid. MS(ESI) m/z 253 ([M-H]'). -62- WO 2005/037279 PCT/US2004/033732 Step 2: In an analogous manner (as Reference Example l-a), (1-hydroxycyclohexyl)-4-( 0 R)-1-phenylethoxyphenyl)acetic acid was prepared from 4-( (1R)-1-phenylethoxyphenyl)acetic acid and cyclohexanone. MS(ESI) m/z 353 ([M-H]) aaaa) Step 1: In an analogous manner to Reference Example l-zzz, step 1 4-( 0 S)-1 -phenylethoxyphenyl)acetic acid was prepared from (4-hydroxyphenyl)acetic acid and R-(+)-sec-phenethyl alcohol. MS(ESI) m/z 253 ([M-H]-). Step 2: In an analogous manner (as Reference Example l-a), (1-hydroxycyclohexyl)-4-( (IS)-1-phenylethoxyphenyl)acetic acid was prepared from 4-( 0S)-1-phenylethoxyphenyl)acetic acid and cyclohexanone. MS(ESI) m/z 353 ([M-H]) Example 1: 1-[1-(3-chloronhenyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0154] Step 1: A solution of (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) (5.4 g, 20.1 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate 04.22 g, 32.15 mmol), and tert-butyl 1-piperazinecarboxylate (5.99 g, 32.15 mmol) in methylene chloride (20 mL) was treated with triethylamine (8.4 mL, 60.3 mmol). The reaction was stirred at 25 °C for 16 h, after which time the solvent was removed in vacuo and the product was purified via Biotage Horizon (FLASH 40 M, silica, gradient from 0% EtOAc/hexane to 30% EtOAc/hexane) to yleld 7.10 g (81%) tort-butyl 4-[(3-chlorophenyl)(1-hydroxycyclohexyl)acctyl]piperazine-1-carboxylate as a white foam. HRMS: calcd for C23H33CIN2O4 436.2129; found (ESI_FT), 437.21996. -63- W0 2005/037279 PCT/US2OO4/OJ37.?2 [0155] Step 2: A solution of 4-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]piperazine- 1-carboxylale (200 mg, 0.46 mmol) in dry te'rahydrofuran (3 mL) under nitrogen was treated dropwise with a solution of borane 0.0 M in tetrahydrofuran, 1.60 mL, 1.60 mmol). The resulting solution was heated at 70 C for 2 h, after which time the reaction was cooled in an ice bath and was treated dropwise with a 2N aqueous solution of hydrochloric acid 0 mL). The reaction was again heated at 70 °C for 1 h, and was then cooled and treated with methanol 0 mL). After the solvent was removed in vacuo, the resulting residue was dissolved in water (5 mL) and was washed with ethyl acetate 0 x 4 mL). The aqueous layer was basified with the addition of a 2 N aqueous solution of sodium hydroxide until the pH = 10. The product was extracted with ethyl acetate (4x5 mL) and the combined organic extracts were dried over magnesium sulfate and concentrated in vacuo to yleld 146 mg (99%) 1-[1-(3-chlorophenv))-2-piperazin-1- ylethylicyclohexanol as a colorless oil. HRMS: calcd for C18H27CIN2O, 322.1812; found (ESi_FT), 323.18977. 1-[1-(3-Chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol 046 mg) was dissolved in methanol (0.5 mL) and treated with a saturated methanolic solution of hydrochloric acid (0.5 mL) followed by diethyl ether. After crystallizing in the refrigerator for 16 h, the resulting solid was collected, washed with diethyl ether and dried in vacuo to yleld 110 mg (60%) 1-[1-(3-chlorophenyl)-2-piperazin-1- ylethyl]cyclohexanol dihydrochloride as a white solid. MS (ESI) m/z 323/325 ([M+H]+); HRMS: calcd for C18H27CIN2O 2.00 HCI, 394.1345; found (ESI..FT), 323.18831. Example 2: 1 -[2-0,4'-bipiperidin-1 '-yl)-1 -(3-chlorophenyl)ethyllcyclohexanol [0156] In an analogous manner to Example 1, step 1 1-[2-0.4'-bipiperidin-1'-yl)-1-(3-chlorophenyl)-2-oxoethyllcyclohexanol was prepared from (3-chlorophenyl)0- dihydrochloride -64- \\ O 2005/037279 PCT/US20O4/033732 hydroxycyclohexyl)acotic acid (Reference Example 1-a) and N-(4-piperidine)piperidine. MS (ESI) m/z 419/421 ([M+Hp; HRMS: calcd for C24H35CIN2O2, 418.2387; found (ESI), 419.2451. [0157] In an analogous manner to Example 1, step 2 1-[2-0,4'-bipiperidin-1'-yl)-1-(3-chlorophenyl)ethyl]cyclohexanol dihydrochloride was prepared from 1 -[2-0,4'-bipiperidin-1'-yl)-1-(3-chlorophenyl)-2-oxoethyl]cyclohexanol. MS (ESI) m/z 405/407 ([M+H]4); HRMS: calcd for C24H37CIN2O 2.00 HCI, 476.2128; found (ESI), 405.2664. Example 3: 1 -[1 -(3-chlorophenyl)-2-(4-pyrro!idin-1 -ylpiperidin-1 -yl)ethyl]cyclohexanol dihydrochloride [0158] In an analogous manner to Example 1, step 1 1 -[1 -(3-chlorophenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)-2-oxoethyl]cyclohexanol was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and 4-0-pyrrolidinyl)piperidine. -65- WO 2005/037279 PCT/US2004/033732 [0159] In an analogous manner to Example 1, step 2 1 -[ 1 -(3-chlorophenyl)-2-(4-pvrrodin-1-ylpiperidin-1-yl)ethyl]cyclohexanoldihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)-2-oxoethyl]cyciohexanol. MS (ESI) m/z391/393 ([M+H]+); HRMS: calcd for C23H35CIN2O 2.00 HCI, 462.1971; found (ESI), 391.2497. Example 4: 1-r,2-0,4'-bipiperidin-1'-yl)-1-(3-bromophenyl)ethyl]cyclohexanol dihydrochloride [0160] In an analogous manner to Example 1, step 1 1-[2-0.4'-bipiperidin-1-yl)-1-(3-bromophenyl)-2-oxoethyl]cyclohexanol was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and N-(4-piperidine)piperidine. MS (ESI) m/z463 ([M+H]*); HRMS: calcd for C24H35BrN2O2, 462.1882; found (ESI), 463.1975. -66- \\O 2005/037279 PCT/US2004/033732 [0161] In an analogous manner to Example 1, step 2 1-[2-0.4'-bipiperidin-1'-yl-1-(3-bromopheny)ethyl]cyclohexanol dihydrochloride was prepared from 1-[2-0,4'-bipiperidin-1'-yl)-1-(3-bromophenyl)-2-oxoethyl]cyclohexanol. MS m/z449/451 ([M-"-H]+); HRMS: calcd for C24H37BrN2O ' 2.00 HCI. 520.1623; found (ESI), 449.2149. Example 5: 1-[1-(2-naphthyl)-2-piperazin-1-ylethyl1cyclobutanol dihydrochloride [0162] In an analogous manner to Example 1. step 1 tert-butyl 4-[0- hydroxycyclobutyl)(2-naphthynacetyl]piperazine-1-carboxylate was prepared from (1-hydroxycyclobutyl)(2-naphthyl)acetic acid (Reference Example 1-c) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C25H32N2O4, 424.2362; found (ESI...FT), 425.24337. [0163] In an analogous manner to Example 1, step 2 1 -[1 -(2-naphthyl)-2-piperazin-1 -ylethyl]cyclobutanol dihyrochloride was prepared from /ert-butyl 4-[(1-hydroxycyclobutyl)(2-naphthyl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C20H26N2O ' 2.00 HCI, 382.1579; found (ESI_FT), 311.21184. Example 6: 1-[2-0.4'-bipiperidin-1'-yl)-1-(3,4-dichlorophenynethyncyclohexanol dihydrochloride -67- \\O 2005/037270 PCT/US2O0./4'033732 [0154] In an analogous manner to Example 1, step 1 1 -[2-0,4'-bipiperidin-1 '-yl)-1 -(3.4-dicrfloropheny)-2-oxoethyl]cyclohexanol was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and N-(4-piperidine)pipcridine. [0165] In an analogous manner to Example 1, step 2 1-[2-0.4'-bipiperidin-1'-yl)-1-(3,4-dichlorophenyl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[2-0,4'-bipiperidin-1'-yl)-1-(3,4-dichlorophenyl)-2-oxoethyl]cyclohexanol. MS m/z 439/441/443 ([M-H]+); HRMS: calcd for C24H35CI2N2O • 2.00 HCI, 510.1738; found (ESI), 439.2267. Example 7: 1 -[1 -(3-bromophenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)ethyl]cyclohexanol dihydrochloride [0166] In an analogous manner to Example 1, step 1 1 -[1 -(3-bromophenyl)-2-oxo-2-(4-pyrrolidin-1-ylpiperidin-1-yl]ethyl]cyclohexanol was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-0-pyrrolidinyl)piperidine. MS (ESI) m/z 449 ([M+H]+); HRMS: calcd for C23H33BrN2O2, 448.1725; found (ESI), 449.1789. [0167] In an analogous manner to Example 1, step 2 1 -[1 -(3-bromophenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(3-bromophenyl)-2-oxo-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)ethyl]cyclohexanol. MS m/z 435/437 ([M+HD; HRMS: calcd for C23H35BrN2O 2.00 HCI, 506.1466; found (ESI), 435.2021. -68- \YO 2005/037279 PCT/US2OO4/033732 Example 8: 1-[2-0,4'rbipiperidin-1'-yl)-1-(3-bromo-4-methoxyphenyl)ethyl]cyclohexanol dihydrochloride [0168] In an analogous manner to Example 1, step 1 1-[2-0,4'-bipiperidin-1'-yl)-1-(3-bromo-4-methoxyphenyl)-2-oxoethyncyclohexanol was prepared from (3-bromo-4-methoxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-1) and N-(4-piperidine)piperidine.. [0169] In an analogous manner to Example 1, step 2 1 -[2-0,4'-bipiperidin-1 '-yl)-1 -(3-bromo-4-methoxyphenyl)ethyncyclohexanol dihydrochloride was prepared from 1-[2-0,4'-bipiperidin-1'-yl)-1-(3,4-dichlorophenyl)-2-oxoethyl]cyclohexanol. MS m/z 479/481 ([M+H]+); HRMS: calcd for C25H39BrN2O2 ' 2.00 HCI, 550.1728; found (ESI), 479.2269. Example 9: 1 -[1 -(3-bromo-4-methoxyphenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)ethyl]cyclohexanol dihydrochloride [0170] In an analogous manner to Example 1, step 1 1 -[1 -(3-bromo-4-methoxyphenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)-2-oxoethyl]cyclohexanol was prepared from (3-bromo-4-methoxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-1) and 4-0-pyrrolidinyl)piperidine. -69- WO 2005/037279 PCT/US2004/033732 [0171] In an analogous manner to Example 1, step 2 1 -[1 -(3-bromo-4-methoxyphenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl1cyclohexanol dihydrochloride was prepared from 1-[1-(3-bromo-4-methoxyphenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)-2-oxoethyl]cyclohexanol. MS m/z 465/467 ([M+H]+); HRMS: calcd for C24H37BrN2O2 2.00 HCI, 536.1572; found (ESI), 465.2096. Example 10: 1-[2-(benzylamino)-1-(3.4-dichlorophenyl)ethy]cyclobutanol hydrochloride [0172] In an analogous manner to Example 1, step 1 N/-benzyl-2-(3.4-dichlorophenyl)-2-0-hydroxvcyclobutyl)acetamide was prepared from (3,4-dichlorophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-p) and benzylamine. HRMS: calcd for C19H19CI2NO2, 363.0793; found (ESl_FT), 364.08658. [0173] In an analogous manner to Example 1, step 2 1 -[2-(benzylamino)-1 -(3,4-dichlorophenyl)ethyl]cyclobutanol hydrochloride was prepared from A/-benzyl-2-(3,4-dichlorophenyl)-2-(1-hydroxycyclobutyl)acetamide. HRMS: calcd for C19H21CI2NO HCI, 385.0767; found (ESI_FT), 350.10832. Example 11: 1-[1-(3,4-dichlorophenyl)-2-(4-pvrrolidin-1-ylpiperidin-1-yl)ethyl]cyclohexanol dihydrochloride -70- WO 2005/037279 PCT/US200-4/033732 [0174] In an analogous manner to Example 1, step 1 1-[1-(3.4-dichlorophenyl)-2-(4-pvrrolidin-1-ylpiperidin-1-yl)-2-oxoethyl]cyclohexanol was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohcxyl)benzeneacetic acid (Reference Example 1-d) and 4-0-pyrrolidinyl)piperidine. [0175] In an analogous manner to Example 1, step 2 1-[1-(3.4-dichlorophenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)ethyl1cyclohexanol dihydrochloride was prepared from 1-[1-(3,4-dichlorophenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)-2-oxoethyl]cyclohexanol. MS m/z 425/427/429 ([M+H]+); HRMS: calcd for C23H34CI2N2O 2.00 HCI, 496.1582; found (ESI), 425.2129. Example 12: 1-[2-(benzviamino)-l-('2-naphihvi)ethnyl)cyclobutanol hydrochloride [0176] In an analogous manner to Example 1, step 1 A/-benzyl-2-0- hydroxycyclobutyl)-2-(2-naphthyl)acetamide was prepared from (1-hydroxycyclobuty!)(2-naphthyl)acetic acid (Reference Example 1-c) and benzylamine. HRMS: calcd for C23H23NO2l 345.1729; found (ESI_FT), 346.17885. [0177] In an analogous manner to Example 1, step 2 1 -[2-(benzylamino)-1 -(2-naphthyl)ethyl]cyclobutanol hydrochloride was prepared from A/-benzyl-2-(1-hydroxycyclobutyl)-2-(2-naphthyl)acetamide. HRMS: calcd for C23H25NO HCI, 367.1703; found (ESI_FT), 332.20146. Example 13: 1 -{1 -(3,4-dichlorophenyl)-2-[4-(methylamino)piperidin-1 -yl]ethyl}cyclohexano! dihydrochloride -71- W0 2005/037279 PCT/US2OO4/O33732 [0178] Step 1: In an analogous manner to Example 1, step 1 /erf-butyl {1-[(3.4-dichlorophenyl)(1-hydroxycyclohexyl)acetyl1piperidin-4-yl)carbamate was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and 4-N-boc-aminopiperidine. MS (ES) m/z 485.2 ([M+H]+); HRMS: calcd for C24H3Cl2N2O4, 484.1896; found (ESI), 485.1987. [0179] Step 2: A solution of fert-butyl {1-[(3,4-dichlorophenyl)0-" hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate (364 mg, 0.75 mmol) in dry tetrahydrofuran 0 mL), under nitrogen, was treated with a solution of borane 0.0 M in tetrahydrofuran, 2.62 mL, 2.62 mmol). The reaction was heated at 74 °C for 2 h, after which time the reaction was cooled and quenched by the addition of methanol (4 mL). The solvents were removed in vacuo, and the products were purified via Biotage Horizon (FLASH 25 M, silica, gradient from 10% EtOAc/hexane to 90% EtOAc/hcxane) to yleld 187 mg (53%) fert-butyl {1-[2-(3,4-dichlorophenyl)-2-0- hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate as a white foam which eluted first and 88 mg (31%) 1-{1-(3,4-dichlorophenyl)-2-[4-(methylamino)piperidin-1- yl]ethyl}cyclohexanol as a colorless oil which eluted second, tert-butyl 0-[2-(3,4- dichlorophenyl)-2-(1-hydroxycyclohexyl)ethynpiperidin-4-yl)carbamate: MS (ES) m/z 471.3 ([M+H]+); HRMS: calcd for C24H36Cl2N2O3 470.2103; found (ESI), 471.2165. 1- 0-(3.4-dichlorophenylyl)-2-[4-(methylamino)piperidin-1-yl]ethyl)cyclohexanol: MS m/z 385/387/389 ([M+H]+). 1-{1-(3,4-dichlorophenyl)-2-[4-(methylamino)piperidin-1- yl]ethyl}cyclohexanol was converted to the dihydrochloride salt with a methanolic solution of hydrochloric acid and diethyl ether to yleld 45 mg (41%) 1-0-(3.4- dichlorophenyl)-2-[4-(methylamino)piperidin-1-yl1ethyl)cyclohexanol dihydrochloride as a white solid. HRMS: calcd for C2oH3oCI2N20 2.00 HCI, 456.1269; found (ESI), 385.183. -72- WO 2005/037279 PCT/US2OO4/O33732 Example 14: 1-[2-(4-aminopiperidin-1-yl)-1-(3,4-dichlorophenyl)ethyl]cyclohexanol dihydrochloride [0180] A solution of tert-butyl {1-[2-(3,4-dichlorophenyl)-2-0- hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate 030 mg, 0.28 mmol) (Example 13), in diethyl ether (2 mL) was treated with a 4 N solution of hydrogen chloride in dioxane 0 mL). The resulting solution was stored at 25 °C for 16 h, during which time crystals began to form. The mixture was transferred to the refrigerator where it was stored for an additional 16 h. The resulting crystals were collected, washed with diethyl ether, and dried in vacuo to yleld 101 mg (82%) 1-2-(4-aminopiperidin-1-yl)-1-(3.4-dichlorophenyl)ethylicyclohexanol dihydrochloride as a white solid. MS m/z 371/373/375 ([M+H]+); HRMS: calcd for C19H28CI2N2O 2.00 HCI, 442.1112; found (ESI), 371.1642. Example 15: 4-[2-(benzylamino)-1 -(3,4-dichlorophenyl)ethyl]-1 -methylpiperidin-4-ol dihydrochloride [0181] In an analogous manner to Example 1, step 1 A/-benzyl-2-(3.4-dichlorophenyl)-2-(4-hydroxy-1-methylpiperidin-4-yl)acetamide was prepared from (3,4-dichlorophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-i) -73- WO 2005/037279 PCT/US2004/033732 and benzylamine. HRMS: calcd for C21H24Cl2N2O2, 406.1215; found (ESI_FT), 40712885. [0182] In an analogous manner to Example 1, step 2 4-[2-(benzylamino)-1-(3.4-dichlorophenyl)ethyl]-1 -methylpiperidin-4-ol dihydrochloride was prepared from N-benzyl-2-(3,4-dichlorophenyl)-2-(4-hydroxy-1-methylpiperidin-4-yl)acetamide. HRMS: calcd for C21H20CI2N2O 2.00 HCI, 464.0956; found (ESI_FT), 393.14924. Example 16: 1-[2-[(3S)-3-aminopyrrolidin-1-yl]-1-(3-chlorophenyl)ethyl]cyclohexanol dihydrochloride [0183] In an analogous manner to Example 1, step 1 ((S)-1 -[2-(3-Chloro-phenyl)-2-(1-hydroxy-cyclohexyl)-acetyn-pyrrolidin-3-yl}-carbamic acid tert-butyl ester was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolodine. [0184] In an analogous manner to Example 1, step 2 1-[2-[(3S)-3-aminopyrrolidin-1-yl]-1 -O-chlorophenyl)ethyl]cyclohexanol dihydrochloride was prepared from {(S)-1-[2-(3-Chloro-phenyl)-2-(1-hydroxy-cyclohexyl)-acetyl]-pyrrolidin-3-yl}-carbamic acid tert-butyl ester. HRMS: calcd for C18H27CIN2O 2.00 HCI, 394.1345; found (ESI), 323.1884. Example 17: 1 -{1 -(3-chlorophenyl)-2-[4-(methylamino)piperidin-1 -yl]ethyl}cyclohexanol dihydrochloride -74- WO 2005/037279 PCT/US2OO4/033732 [0185] In an analogous manner to Example 1, step 1 tert-butyl 0-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl)carbamate was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and 4-N-boc-aminopiperidine. MS m/z 451/453 ([M+H]+) HRMS: calcd for C24H35ClN2O4, 450.2285; found (ESI), 451.2353. [0186] In an analogous manner to Example 13, step 2 1 -0 -(3-chlorophenyl)-2-[4-(methylamino)piperidin-1 -yl]ethyl}cyclohexanol dihydrochloride was prepared from tert-butyl {1-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS m/z 351/353 ([M+H]+); HRMS: calcd for C2oH31CIN20 2.00 HCI, 422.1658; found (ESI), 351.2208. Example 18:1 -[2-(4-aminopiperidin-1 -yl)-1 -(3-bromophenyl)ethyl]cyclohexanol dihydrochloride [0187] In an analogous manner to Example 1, step 1 tert-butyl 0-[(3-bromophenyl)0-hydroxvcyclohexyl)acetyl1piperidin-4-yl)carbamate was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-N-boc-aminopiperidine. MS (ES) m/z 495.2 ([M+H]+); HRMS: calcd for C24H35BrN2O4, 494.1780; found (ESI), 495.1864. -75- WO 2005/037279 PCT/US2OO4/033732 [01881 In an analogous manner to Example 13, step 2 tert-butyl 0-[2-(3- bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-yl)carbamate was prepared from tert-butyl {1 -[(3-bromophenylphenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4- yl}carbamate. MS (ES) m/z 481.3 ([M+H]+); HRMS: calcd for C24H37BrN2O3, 480.1988; found (ESI), 481.2081. [0189] In an analogous manner to Example 14, 1-[2-(4-aminopiperidin-1-yl)-1-(3-bromophenyl)ethyl]cyclohexanol dihydrochloride was prepared from tert-butyl {1-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate. HRMS: calcd for C19H29BrN2O 2.00 HCI, 452.0997; found (ESI), 381.1525. Example 19: 1-{1-(3-bromophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride [0190] In an analogous manner to Example 1, step 1 tert-butyl {1-[(3-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl)carbamate was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-N-boc-aminopiperidine. MS (ES) m/z 495.2 ([M+H]+); HRMS: calcd for C24H35BrN2O4, 494.1780; found (ESI), 495.1864. [0191] In an analogous manner to Example 13, step 2 1-{1-(3-bromophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride was prepared from tert-butyl {1 -[(3-bromophenylpheny!)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS (ESI) m/z 395 ([M+H]+); HRMS: calcd for C2oH31BrNO • 2.00 HCI, 466.1153; found (ESI), 395.1708. -76- \YL) 2OO5/037279 PCT/US2004/033732 Example 20: 1-{2-0,4'-bipiperidin-1'-y|)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohGxanol dihydrochloride [0192] In an analogous manner to Example 1, step 1 1 -(2-0,4'-bipiperidin-1 '-yl)-1 -[3-(trifluoromethyl)phenyl]-2-oxoethyl)cyclohexanol was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and N-(4-piperidine)piperidine. [0193] In an analogous manner to Example 1, step 2 1-(2-0.4'-bipiperidin-1'-yl)-1-[3- (trifluoromethyl)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from 0- hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid. m/z 439 ([M+H]+); HRMS: calcd for C25M37[3N2O 2.00 HCI, 510.2392; found (ESI), 439.2928. Example 21: 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0194] In an analogous manner to Example 1, step 1 /erf-butyl 4-f0- hydroxycyclohexyl)0-naththy)acetyl]piperazine-1-carboxylate was prepared from (1-hydroxycyc)ohexyl)(1-naphthyl)acetic acid (Reference Example 1-e) and tert-butyl 1- -77- W O 2005/037279 PCT/US2004/033732 piperazinecarboxylate. MS (ESI) m/z 453 ([M+H]+); HRMS: calcd for C27H36N2O4, 452.PJ575; found (ESI FT), 453.27518. [0195] In an analogous manner to Example 1, step 2 1-[1-(1-naphthyl)-2-piperazin-1-ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[(1-hydroxycyclohexyl)(1-naphthyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 339 ([M+H]+); HRMS: calcd for C22H30N2O HCI, 374.2125; found (ESI_FT), 339.24268. Example 22: 1-[2-0,4'-bipiperidin-1'-yl)-1-(2-naphthyl)ethyl]cyclohexano! dihydrochloride [0196] In an analogous manner to Example 1, step 1 1-[2-0.4'-bipiperidin-1'-yl)-1-(2-naphthyl)-2-oxoethy]cyclohexanol was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and N-(4-piperidine)piperidine. [0197] In an analogous manner to Example 1, step 2 1-[2-0,4'-bipiperidin-1'-yl)-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[2-0,4'-bipiperidin-1'-yl)-1-(2-naphthyl)-2-oxoethyl]cyclohexanol. MS m/z 421 ([M+H]'); HRMS: calcd for C28H40N2O 2.00 HCI, 492.2674; found (ESI), 421.3224. Example 23: 1-(2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride -78- WO 2005/037279 PCT/US2004/033732 [0198] In an analogous manner to Example 1, step 1 tert-butyl 4-10- hydrcxycyclohexyl)[3-(trifluoromeethoxy)phenyl]acetyl)pipernzine-1-carboxylate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C24H33[3N2O5, 485.2342; found (ESI), 487.2398. [0199] In an analogous manner to Example 1, step 2 1 -{2-piperazin-1 -yl-1 -[3-(trifluoromethoxy)phenynethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}piperazine-1-carboxylate. HRMS: calcd for C19H27[3N2O2 2.00 HCI, 444.1558; found (ESI), 373.2095. Example 24: 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifJuoromethoxy)phGnyl]ethyl}cyclohexanol dihydrochloride [0200] A solution of 1-{2-piperazin-1-yl-1-[3- (trifluoromethoxy)phenyl]ethyl}cyclohexanol (590 mg, 1.59 mmol) (see Example 23), in formic acid (3.1 mL) at 50 °C, was treated with an aqueous solution of formaldehyde (37% in water, 1.3 mL, 1.94 mmol). The reaction was heated at 70 °C for 1.5 h, after which time the reaction was poured into water (50 mL) and basified to pH = 10 with the addition of a 2 N aqueous solution of sodium hydroxide. The product was then extracted with ethyl acetate (3 x 20 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated to yleld 442 mg (72%) 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol as a colorless oil. The product was dissolved in methanol (0.5 mL) and the resulting solution was treated with a saturated methanolic solution of hydrochloric acid (0.5 mL) followed by diethyl ether (2 mL). The solution was stored in the refrigerator for 16 h. The resulting -79- WO 2005/037279 PCT/US2OO4/O33732 precipitate was filtered and washed with diethyl ether to yleld 299 mg (57%) 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride as a white solid. HRMS: calcd for C20H29F2N2O2 2.00 HCl, 458.1715; found (ESI), 387.2263. Example 25: 1-[2-(4-aminopiperidin-1-yl)-1-(3-bromo-4-methoxyphenyl)ethyl]cyclohexanol dihydrochloride [0201] In an analogous manner to Example 1, step 1 tert-butyl {1-{(3-bromo-4-methoxyphenyl)(1-hydroxycyclohexyl).acetyl]piperidin-4-yl}carbamate was prepared from (3-bromo-4-methoxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-1) and 4-N-boc-aminopiperidine. MS (ES) m/z 525.2 ([M+H]+); HRMS: calcd for C25H37BrN2O5, 524.1886; found (ESI), 525.1971. [0202] In an analogous manner to Example 13, step 2 tert-butyl {1-[2-(3-bromo-4-methoxyphenyl)-2-(1-hydroxycyc)ohexyl)ethyl]piperidin-4-yl}carbamate was prepared from /erf-butyl {1 -[(3-bromo-4-methoxyphenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-y]}carbamate. MS (ES) m/z 511.4 ([M+H]+); HRMS: calcd for C25H39BrN2O4, 510.2093; found (ESI), 511.2147. [0203] In an analogous manner to Example 14, 1-[2-(4-aminopiperidin-1-yl)-1-(3-bromo-4-methoxyphenyl)ethyl]cyclohexanol dihydrochloride was prepared from tert-butyl {1 -[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate. MS m/z 411/413 ([M+H]+); HRMS: calcd for C2oH31BrN202 2.00 HCl, 482.1102; found (ESI), 411.1656. -80- WO 2OO5/0J7279 PCT/U'S200-l/OJ3732 Example 26: 1-{2-(4-pyrrolidin-1-ylpiperidin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride [0204] In an analogous manner to Example 1, step 1 1 -(2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)-1 -[3-(trifluoromethyl)phenyl]-2-oxoethy))cyclohexanol was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetic acid (Reference Example 1-m) and 4-0 -pynolidinyl)piperidine. [0205] In an analogous manner to Example 1, step 2 1-{2-(4-pyrrolidin-1-ylpiperidin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride was prepared from 1-{2-(4-pyrrolidin-1-ylpiperidin-1-yl)-1-[3-(trifluoromethyl)phenyl]-2-oxoethyl}cyclohexanol. MS m/z425 ([M+H]+); HRMS: calcd for C24H35[3N2O 2.00 HCI, 496.2235; found (ESI), 425.2789. Example 27: 1-{1-[4-(benzy!oxy)phenyl]-2-piperazin-1-ylethy!}cyclohexano! dihydrochloride [0206] In an analogous manner to Example 1, step 1 tert-butyl 4-[{4- (benzyloxyl)phenyn(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate was prepared from (4-benzyloxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-n) and -81- WO 2OO5/037279 PCT/US2OO4/O33732 tort-butyl 1-piperazinecarboxylate. MS (ESI) m/z 509 ([M+H]+); HRMS: calcd for C30H40N2O5, 508.2937; found (ESI), 509.3027. [0207] In an analogous manner to Example 1, step 1-{1-[4-(benzyloxy)phenyl]-2-pipcrazin-1-ylethyl}cyclohexanol dihydrochloride was prepared from tert-butyl 4-[[4-(benzyloxy)phenyl](1-hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate. HRMS: calcd for C25H34N2O2 2.00 HCI, 466.2154; found (ESI), 395.2683. Example 28: 1 -{2-piperazin-1 -yl-1 -[4-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride [0208] In an analogous manner to Example 1, step 1 tert-butyl 4-{0- hydroxycyclohexyl)[4-(trifluoromethoxy)phenyl]acetyl)piperazine-1-carboxylate was prepared from (1-hydroxycyclohexyl)[4-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-g) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 487 ([M+H]+). [0209] In an analogous manner to Example 1, step 2 1-{2-piperazin-1-yl-1-[4-(trifluoromethoxy)phenyl]ethy!}cyclohexanol dihydrochloride was prepared from tert-butyl 4-{(1-hydroxycyclohexyl)[4-(triftuoromethoxy)phenyl]acetyl}piperazine-1-carboxylate. MS m/z 373 ([M+H]); Anal. Calcd for C19H27[3N2O2 2.00 HCI 2.10 H2O: C, 47.23; H, 6.93; N, 5.80. Found: C, 46.93; H, 6.80. Example 29: 1 -{1 -(3-bromo-4-methoxyphenyl)-2-[4-(methylamino)piperidin-1 -yl]ethyl}cyclohexanol dihydrochloride -82- W'O 2005/037279 PCT/US2O04/O33732 [0210] In an analogous manner to Example 1, step 1 tert-butyl 0-[(3-bromo-4-methoxyphenyl)0-hydroycyclohexyl)acetyl]piperidin-4-yl}carbamate was prepared from (3-bromo-4-methoxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-1) and 4-N-boc-aminopiperidine. MS (ES) m/z 525.2 ([M+H]4); HRMS: calcd for C25H37BrN2O5, 524.1886; found (ESI), 525.1971. [0211] In an analogous manner to Example 13, step 2 1-{1-(3-bromo-4- methoxypheny!)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride was prepared from /erf-butyl {1-[(3-bromo-4-methoxyphenyl)0- hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS (ESI) m/z 425 ([M+H]+); HRMS: calcd for C21H33BrN2O2 2.00 HCI, 496.1259; found (ESI), 425.1793. Example 30: 1-{2-[4-(methylamino)piperidin-1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride [0212] In an analogous manner to Example 1, step 1 tert-butyl 0-10- hydroxycyclohexyl)[3-(trifluoromethyl)phenyl1acetyl)piperidin-4-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetic acid (Reference Example 1-m) and 4-N-boc-aminopiperidine. MS (ES) m/z485.3 ([M+H]+); HRMS: calcd for C25H35[3N2O4, 484.2549; found (ESI), 485.2612. -83- WO 2005/037279 PCT/U'S2OO4/033732 [0213] In an analogous manner to Example 13, step 2 1-{2-[4-(methylamino)piperidin- 1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride was prepared from /erf-butyl 0 -{(1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetyl}piperidin-4- yl)carbamate. MS m/z 385 ([M+H]+); HRMS: calcd for C21H31[3N2O 2.00 HCI, 456.1922; found (ESI), 385.2454. Example 31: 1 -[1 -(2-naphthyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)ethyl]cyclohexanol dihydrochloride [0214] In an analogous manner to Example 1, step 1 141 -(2-naphthyl)-2-(4-Dyrrolidin-1 -ylpiperidin-1 -yl)-2-oxoethyncyclohexanol was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and 4-0-pyrrolidinyl)piperidine. [0215] In an analogous manner to Example 1, step 2 1-[1-(2-naphthyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(2-naphthyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)-2-oxoethyl]cyclohexanol. MS m/z 407 ([M+H]+); HRMS: calcd for C27H38N2O 2.00 HCI, 478.2518; found (ESI), 407.3055. Example 32: 1-[2-(4-aminopiperidin-1-yl)-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride -84- WO 2005/037279 PCT/US2004/033732 [0216] In an analogous manner to Example 1, step 1 rert-butyl 0-[0- hydroxycyclohexyl)(2-naphthyl)acetyl]piperidin-4-yllcarbarnate was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and 4-N-boc-aminopiperidine. MS (ES) m/z 467.3 ([M+H]+); HRMS: calcd for C28H38N2O4, 466.2832; found (ESI), 467.2902. [0217] In an analogous manner to Example 13, step 2 t ert-butyl 0-|2-0- hydroxvcyclohexyl)-2-(2-naphthyl)ethyl)piperidin-4-yl)carbamate was prepared from /erf-butyl {1-[(1-hydroxycyclohexyl)(2-naphthyl)acetyl]piperidin-4-yl}carbamate. MS (ES) m/z 453.4 ([M+H]+); HRMS: calcd for C26H40N2O3, 452.3039; found (ESI), 453.3095. [0218] In an analogous manner to Example 14, 1-[2-(4-aminopiperidin-1-yl)-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from /erf-butyl 0-[2-(1-hydroxycyclohexyl)-2-(2-naphthyl)ethyl]piperidin-4-yl}carbamate. MS m/z 353 ([M+H]+); HRMS: calcd for C23H32N2O 2.00 HCI, 424.2048; found (ESI), 353.2598. Example 33: 1-[2-[(3-chlorobenzyl)amino]-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride [0219] In an analogous manner to Example 1, step 1 N-(3-chlorobenzyl)-2-0- hydroxycyclohexyl)-2-(2-naphthyl)acetamide was prepared from 0- hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and 3-chlorobenzylamine. MS (ESI) m/z408/410 ([M+H]+). [0220] In an analogous manner to Example 1, step 2 1-[2-[(3-chlorobenzyl)amino]-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride was prepared from N-(3-chlorobenzyl)-2- -85- WO 2005/037279 PCT/US2OO4/033732 (1-hydroxycyclohexyl)-2-(2-naphthyl)acetamide. MS m/z 394/396 ([M+H]+); HRMS: calcd or C25H28CINO HCI, 429.1626; found (ESI), 394.191. Example 34: 1-[1-(3-chlorophenyl)-2-pyrrolidin-1-ylethyl]cyclohexanol hydrochloride [0221] In an analogous manner to Example 1, step 1 1 -[1-(3-chlorophenyl)-2-oxo-2-pyrrolidin-1-ylethyl]cyclohexanol was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and pyrrolidine. MS (ESI) m/z 322/324 ([M+HD; HRMS: calcd for C18H24CINO2, 321.1496; found (ESI_FT), 322.15603. [0222] In an analogous manner to Example 1, step 2 1-[1-(3-chlorophenyl)-2-pyrrolidin-1-ylethyl]cyclohexanol hydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-oxo-2-pyrrolidin-1-ylethyl]cyclohexanol. HRMS: calcd for C18H26CINO HCI, 343.1470; found (ESI_FT), 308.17736. [0223] In an analogous manner to Example 1, step 1 tert-butyl 0 -[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl]carbamate was prepared from (3- Example 35: 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3-chlorophenyl)ethyl]cyclohexanol dihydrochloride -86- W O 2005/037279 PCT/US2OO4/033732 chlorophenyl)0-hyclroxycyclohexyl)acetic acid (Reference Example 1-a) and 4-N-boc-aminopiperidine. MS m/z 451/453 ([M+H]+); HRMS: calcd for C24H35CIN2O4, 450.2285; found (ESI), 451.2353. [0224] In an analogous manner to Example 13, step 2 1-[2-(4-aminopiperidin-1-yl)-1-(3-chlorophenyl)ethyl]cyclohexanol dihydrochloride was prepared from tert-butyl {1-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS m/z 337/339 ([M+H]+); HRMS: calcd for C19H29CIN2O 2.00 HCI, 408.1502; found (ESI), 337.2022 Example 36: 1-{1-(3-chlorophenyl)-2-[4-(dimethylamino)piperidin-1 -yl]ethyl}cyc!ohexanol dihydrochloride [0225] A solution o[1-[2-(4-aminopiperidin-1-yl)-1-(3-chlorophenyl)ethyl]cyclohexanol (50 mg, 0.15 mmol) (see Example 35), in formic acid (0.28 mL) was treated with an aqueous solution of formaldehyde (37% in water, 0.12 mL). The reaction was heated at 70 °C for 1 h, after which time the reaction was diluted with water (3 mL) and basified to pH = 10 with a 2 N aqueous solution of sodium hydroxide. The product was extracted with ethyl acetate (4x5 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated in vacuo. The resulting colorless oil was treated with methanolic hydrochloric acid and diethyl ether to yleld 32 mg (53%) 1-{1-(3-chlorophenyl)-2-[4-(dimethylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride as a white solid. HRMS: calcd for C21H33CIN2O HCI, 400.2048; found (ESI), 365.2349. Example 37: 4-[1-(3,4-dichlorophenyl)-2-piperazin-1-ylethyl]-1-methylpiperidin-4-ol trihydrochloride -87- W0 2OO5/037279 PCT/US2004/033732 [0226] In an analogous manner to Example 1, step 1 tert-butyl 4-[(3.4- dichlorophenyl)4-hydroxy-1-methylpiperidin-4-yl)acetyl]piperazine-1-carboxylate was prepared from (3,4-dichlorophcnyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-i) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C23H33CI2N3O4, 485.1848; found (ESLFT), 486.19305. [0227] In an analogous manner to Example 1, step 2 4-[1-(3,4-dichlorophonyl)-2-piperazin-1-ylethyl]-1-methylpiperidin-4-ol trihydrochloride was prepared from tert-butyl 4-[(3,4-dichlorophenyl)(4-hydroxy-1-melhylpiperidin-4-yl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C18H27CI2N3O 3.00 HCI, 479.0831; found (ES!_FT), 372.16065. Example 38: 1-[2-(benzylamino)-1-(3,4-dichlorophenyl)ethyl]cyclohexanol hydrochloride [0228] In an analogous manner to Example 1, step 1 N-benzyl-2-(3.4-dichlorophenyl)-2-(1-hydroxycyclohexyl)acetamide was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and benzylamine. HRMS: calcd for C21H23CI2NO=, 391.1106; found (ESLFT), 392.11598. [0229] In an analogous manner to Example 1, step 2 4-[1-(3,4-dichlorophenyl)-2-piperazin-1-ylethyl]-1-methylpiperidin-4-ol hydrochloride was prepared from N-benzyl-2-(3,4-dich!orophenyl)-2-(1-hydroxycyclohexyl)acetamide. HRMS: calcd for C21H25CI2NO HCI, 413.1080; found (ESLFT), 378.13864. -88- WO 2005/037279 PCT/US2004/033732 Example 39: 1-{2-(4-aminopiperidin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride [0230] In an analogous manner to Example 1, step 1 tert-butyl 0-{0- hydroxycyclohexl)[3-(trifluoromethyl)phenynacetyl]Piperidin-4-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetic acid (Reference Example 1-m) and 4-N-boc-aminopiperidine. MS (ES) m/z 485.3 ([M+H]+); HRMS: calcd for C25H35[3N2O4, 484.2549; found (ESI), 485.2612. [0231] In an analogous manner to Example 13, step 2 fe/t-butyl 0-(2-0- hydroxycyclohexyl)-2-[3-(trifluoromethyl)phenyl1ethyl)piperidin-4-yl)carbamate was prepared from tert-butyl 0-{(1-hydroxycyclohexyl)[3- (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)carbamate. MS (ES) m/z 471.4 ([M+H]+); HRMS: calcd for C25H37[3N2O3, 470.2756; found (ESI), 471.2852. [0232] In an analogous manner to Example 14, 1-{2-(4-aminopiperidin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride was prepared from tert-butyl 0-{2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethyl)phenyl]ethyl}piperidin-4-yl)carbamate. MS m/z 371 ([M+H]+); HRMS: calcd for C20H29[3N2O • 2.00 HCI, 442.1766; found (ESI), 371.2309. Example 40: 1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclobutanol hydrochloride -89- WO 2005/037279 PCT/US2OO4/033732 [0233] In an analogous manner to Example 1, step 1 N-benzyl-2-(3-bromophenyl)-2-0-hydroxvcyclobutyl)acetamide was prepared from (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and benzylamine. HRMS: calcd for C19H2oBrN02, 373.0677; found (ESI_FT), 374.07415. [0234] In an analogous manner to Example 1, step 2 1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclobutanol hydrochloride was prepared from N-benzyl-2-(3-bromophenyl)-2-(1-hydroxycyclobutyl)acetamide. HRMS: calcd for C19H22BrNO HCI, 395.0652; found (ESI_FT), 360.09546. Example 41: 1-[2-(benzylamino)-1-(3-chlorophenyl)ethyl]cyclohexanol hydrochloride [0235] In an analogous manner to Example 1, step 1 N-benzyl-2-(3-chlorophenyl)-2-(1-hydroxycyclohexyl)acetamide was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and benzylamine. HRMS: calcd for C21H24CINO2, 357.1496; found (ESLFT), 358.15607. [0236] In an analogous manner to Example 1, step 2 1-[2-(benzylamino)-1-(3-chlorophenyl)ethyl]cyclohexanol hydrochloride was prepared from A/-benzyl-2-(3- -90- WO 2005/037279 PCT/US2004/033732 chlorophenyl)-2-(1-hydroxycyclohcxyl)acetamide. HRMS: calcd for C21H26CINO HCI, 379 1470; found (ESI..FT). 344.17761. Example 42: 1-[2-(cyclohexylamino)-1-(3,4-dichlorophenyl)ethyl]cyclohexanol hydrochloride [0237] In an analogous manner to Example 1, step 1 N-cyclohexyl-2-(3.4- dichlorophenyl)-2-(1-hydroxycyclohexyl)acetamide was prepared from 3,4-dichloro-a!pha-(1-hydroxycyciohexyl)benzeneacetic acid (Reference Example 1-d) and cyclohexylamine. MS (ESI) m/z 384/386/388 ([M+H]+). [0238] In an analogous manner to Example 1, step 2 1-[2-(cyclohexylamino)-1-(3,4- dichlorophenyl)ethyl)cyclohexanol hydrochloride was prepared from N-cyclohexyl-2-(3,4- dichlorophenyl)-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z [M+H]+ (370/372/374); HRMS: calcd for C20H29CI2NO HCI, 405.1393; found (ESI), 370.1687; Anal. Calcd for C20H29CI2NO HCI: C, 59.05; H, 7.43; N, 3.44. Found: C, 59.00; H, 7.49; N, 3.37. Example 43: 1-[2-(4-aminopiperidin-1-yl)-1-(1-naphthyl)ethyl]cyclobutanol dihydrochloride -91- WO 2005/037279 PCT/US2004/033732 [0239] In an analogous manner to Example 1, step 1 fort-butyl [1-[L1i hydroxycyclobutyl)(1-naphthyl)acotylpiperidin-4-yl}carbamate was prepared from 0- hydroxycyclobutyl)(1-naphthy!)acetic acid (Reference Example 1-o) and 4-N-boc- aminopiperidine. MS (ES) m/z 439.3 ([M+H]+). [0240] In an analogous manner to Example 1, step 2 1-[2-(4-aminopiperidin-1-yl)-1-(1-naphthyl)ethyl]cyclobutanol dihydrochloride was prepared from tort-butyl {1-[(1-hydroxycyclobutyl)(1-naphthyl)acetyl]piperidin-4-yl}carbamate. MS (ES) m/z 325.3 ([M+H]+); HRMS: calcd for C21H28N2O 2.00 HCI, 396.1735; found (ESI), 325.2272. Example 44: 4-[2-(benzylamino)-1-(3-bromophenyl)ethyl]-1-methylpiperidin-4-ol dihydrochloride [0241] In an analogous manner to Example 1, step 1 N-benzyl-2-(3-bromophenyl)-2-(4-hydroxy-1-methylpiperidin-4-yl)acetamide was prepared from (3-bromophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-r) and benzylamine. HRMS: calcd for C21H25BrN2O2, 416.1099; found (ESI_FT), 417.11652. [0242] In an analogous manner to Example 1, step 2 4-[2-(benzylamino)-1-(3-bromophenyl)ethyl]-1-methylpiperidin-4-ol dihydrochloride was prepared from N-benzyl-2-(3-bromophenyl)-2-(4-hydroxy-1-methylpiperidin-4-yl)acetamide. HRMS: calcd for C21H27BrN2O 2.00 HCI, 474.0840; found (ESI_FT), 403.13802. Example 45: 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclopentanol dihydrochloride -92- WO 2005/037279 PCT/US2004/033732 [0243] In an analogous manner to Example 1, step 1 tert-butyl 4-[0- hydroxycydopentyl)(1-naphthyl)acetyripiperazine-i-carboxylate was prepared from (1-hydroxycyclopentyl)(1-naphthyl)acetic acid (Reference Example 1-s) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 439 ([M+H]+); HRMS: calcd for C26H34N2O4, 438.2519; found (ESI), 439.2563. [0244] In an analogous manner to Example 1, step 2 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyciopentanol dihydrochlorids was prepared from tert-buty\ 4-[(1-hydroxycyclopentyl)(1-naphthyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 325 ([M+H]+); HRMS: calcd for C21H28N2O 2.00 HCI, 396.1735; found (ESI), 325.2267. Example 46: 1-{2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclobutanol dihydrochloride [0245] In an analogous manner to Example 1, step 1 tert-butyl 4-(0- hydroxycyclobutyl)[3-(trifluoromethoxy)phenyl]acetyl)piperazinG-1-carboxylate was prepared from (1-hydroxycyclobutyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-k) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C22H29[3N2O5, 458.2029; found (ESI), 459.2118. -93- WO 2005/037279 PCT/US2004/033732 [0246] In an analogous manner to Example 1, step 2 1-{2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclobutanol dihydrochloride was prepared from tert-butyl 4-{(1-hydroxycyclobutyl)[3-(trifluoromethoxy)phenyljacetyl}piperazine-1-carboxylate. HRMS: calcd for C.7H23[3N2O2 2.00 HCI, 416.1245; found (ESI), 345.1801. Example 47: 1 -{2-[(4-fluorobenzyl)amino]-1 -[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol hydrochloride [0247] In an analogous manner to Example 1, step 1 N-(4-fluorobenzyl)-2-0 -hydroxycyclohexyl)-2-[3-(trifluoromethyl)phenyl)acetarnide was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetic acid (Reference Example 1-m) and 4-fluorobenzylamine. MS (ESI) m/z410 ([M+H]+)- [0248] In an analogous manner to Example 1, step 2 1-{2-[(4-fluorobenzyl)amino]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol hydrochloride was prepared from N-(4-fluorobenzyl)-2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethyl)phenyl]acetamide. MS (ESI) m/z 396 ([M+H]+); HRMS: calcd for C22H25[4NO HCI, 431.1639; found (ESI), 396.1931. Example 48: 1-[1-(3-bromophenyl)-2-(cyclohexylamino)ethyl]cyclohexanol hydrochloride -94- WO 2005/037279 PCT/US2004/033732 [0249] In an analogous manner to Example 1, step 1 2-(3-bromoPhenyl)-N-cyclohexyl-2-(1-hydroxycyclohexyl)acetamide was prepared from (3-bromopheny!)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and cyclohexylamine. MS (ESI) m/z394/396 ([M+H]). [0250] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2-(cyclohexylamino)ethyl]cyclohexanol hydrochloride was prepared from 2-(3-bromophenyl)-A/-cyclohexyl-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z 380/382 ([M+H]); HRMS: calcd for C20H3oBrNO HCI, 415.1278; found (ESI), 380.1574. Example 49: 1 -[2-[4-(methylamino)piperidin-1 -yl]-1 -(2-naphthyl)ethyl]cyclohexanol dihydrochloride [0251] In an analogous manner to Example 1, step 1 tert-butyl 0-f0- hydroxycyclohexyl)(2-naphthyl)acetyl]piperidin-4-yl)carbamate was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-c) and 4-N-boc-aminopiperidine. MS (ES) m/z 467.3 ([M+H]+); HRMS: calcd for C28H38N2O4, 466.2832; found (ESI), 467.2902. [0252] In an analogous manner to Example 13, step 2 1-[2-[4-(methylarnino)piperidin- 1-yl]-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 0- [(1-hydroxycyclohexyl)(2-naphthyl)acetyl]piperidin-4-yl}carbamate. MS m/z 367 ([M+H]+); HRMS: calcd for C24H34N=O 2.00 HCI, 438.2205; found (ESI), 367.2763. Example 50: 2-(3-bromophenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol dihydrochloride -95- WO 2005/037279 PCT/US2O04/033732 [0253] In an analogous manner to Example 1, step 1 tert-butyl 4-[2-(3-bromophenyl)-3-elhyl-3-hydroxypentanoyl]piperazine-1-carboxylate was prepared from 2-(3-bromophenyl)-3-ethyl-3-hydroxypentanoic acid (Reference Example 1-t) and tert-buty) 1-piperazinecarboxylate. MS (ESI) m/z469/471 ([M+H]f); HRMS: calcd for C22H33BrN2O4, 468.1624; found (ESI_FT), 469.17071. [0254] In an analogous manner to Example 1, step 2 2-(3-bromophenyl)-3-ethyl-1-piperazin-1-ylpentan-3-o! dihydrochioride was prepared from /erf-butyl 4-[2-(3-bromophenyl)-3-ethyl-3-hydroxypentanoyl]piperazine-1-carboxylate. MS (ESI) m/z 355/357 ([M+H]+); HRMS: calcd for C17H27BrN2O 2.00 HCI, 426.0840; found (ESI_FT), 355.13878. Example 51: 4-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]heptan-4-ol dihydrochioride [0255] In an analogous manner to Example 1, step 1 tert-butyl 4-[2-(3-chlorophenvy)-3-hydroxy-3-propylhexanoyl1piperazine-1-carboxylate was prepared from 2-(3-chlorophenyl)-3-hydroxy-3-propylhexanoic acid (Reference Example 1-u) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 453/455 ([M+H]+); HRMS: calcd for C24H37CIN2O4, 452.2442; found (ESI_FT), 453.25255. -96- WO 2005/037279 PCT/US2004/033732 [0256] In an analogous manner to Example 1, step 2 4-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]heptan-4-ol dihydrochloride was prepared from tert-butyl 4-[2-(3-chlorophenyl)-3-hydroxy-3-propylhexanoyl]piperazine-1-carboxylate. MS (ESI) m/z 339/341 ([M+H]+); HRMS: calcd for C19H3,CIN2O * 2.00 HCI, 410.1658; found (ESI_FT), 339.21916. Example 52: 2-(3-chlorophenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol dihydrochloride [0257] In an analogous manner to Example 1, step 1 rert-buty! 4-[2-(3-chlorophenyl)-3-ethyl-3-hydroxyl)entanoyl]piperazine-1-carboxylate was prepared from 2-(3-chlorophenyl)-3-ethyl-3-hydroxypentanoic acid (Reference Example 1-v) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z425/427 ([M+H]+). [0258] In an analogous manner to Example 1, step 2 2-(3-chlorophenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol dihydrochloride was prepared from tert-butyl 4-[2-(3-chlorophenyl)-3-ethyl-3-hydroxypentanoyl]piperazine-1-carboxylate. MS (ESI) m/z 311/313 ([M+H]+); HRMS: calcd for C17H27CIN2O HCI, 346.1579; found (ESI_FT), 311.18803. Example 53: 3-ethyl-2-(1-naphthyl)-1-piperazin-1-ylpentan-3-ol dihydrochloride -97- WO 2005/037279 PCT/US2004/033732 [0259] In an analogous manner to Example 1, step 1 tert-butyl 4-[2-(3-chlorophenyl)-3-ethyl-3-hydroxypentanoyl]piperazine-1-carboxylate was prepared from 3-ethyl-3-hydroxy-2-(1-naphthyl)pentanoic acid (Reference Example 1-w) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 441.2766 ([M+H]+); HRMS: calcd for C26H36N2O4 440.2675; found (ESI), 441.2766. [0260] In an analogous manner \o Example 1, step 2 3-ethyl-2-(1-naphthyl)-1-piperazin-1-ylpentan-3-ol dihydrochloride was prepared from tert-butyl 4-[2-(3-chlorophenyl)-3-ethyl-3-hydroxypentanoyl]piperazine-1-carboxylate. MS (ESI) m/z 327 ([M+H]+); HRMS: calcd for C21H3oN20 2.00 HCI, 398.1892; found (ESI), 327.2426. Example 54: 1 -[2-(4-aminopiperidin-1 -y!)-1-(1 -naphthyl)elhyl]cyciohexanoi dihydrochloride [0261] In an analogous manner to Example 1, step 1 tert-butyl 0-[0- hydroxycyclohexyl)(1-naphthyl)acetyl]piperidin-4-yl)carbamate was prepared from (1-hydroxycyclohexyl)(1-naphthyl)acetic acid (Reference Example 1-e) and 4-N-boc-aminopiperidine. MS (ESI) m/z 467 ([M+H]+). [0262] In an analogous manner to Example 1, step 2 1-[2-(4-aminopiperidin-1-yl)-1-(1-naphthyl)ethyl]cyclonexanol dihydrochloride was prepared from tert-butyl {1-[(1-hydroxycyclohexyl)(1-naphthyl)acetyl]piperidin-4-yl}carbamate. MS (ESI) m/z 353 ([M+H]+); HRMS: calcd for C23H32N2O 2.00 HCI, 424.2048; found (ESI), 353.2583. Example 55: 1-[1-(3-bromophenyl)-2-0,2,3,4-tetrahydronaphthalen-1-ylamino)ethyl]cyclohexanol hydrochloride -98- WO 2005/037279 PCT/US2004/033732 [0263] In an analogous manner to Example 1, step 1 2-(3-bromophenyl)-2-0 -hydroxycyclohexyl)-N-1.2.3.4-tetrahydronaphthalen-1-ylacetamide was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 1,2,3,4-tetrahydro-1-napthylamine. MS (ESI) m/z 442/444 ([M+H]+). [0264] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2-0,2,3,4-tetrahydronaphthalen-1-ylamino)ethyl]cyclohexanol hydrochloride was prepared from 2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)-/V-1,2,3,4-tetrahydronaphthalen-1-ylacetamide. MS (ESI) m/z 428/430 ([M+Hf); HRMS: calcd for C24H30BrNO HCI, 463.1278; found (ESI), 428.1593. Example 56: 1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclopentanol dihydrochloride [0265] In an analogous manner to Example 1, step 1 1 -[2-(4-methylpiperazin-1 -yl)-1 -(1 -naphthyl)-2-oxoethyl]cyclopentanol was prepared from (1-hydroxycyclopentyl)(1-naphthyl)acetic acid (Reference Example 1-s) and N-methylpiperazine. MS (ESI) m/z 353 ([M+H]+). -99- WO 2005/037279 PCT/US20O4/033732 [0266] In an analogous manner to Example 1, step 2 1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclopentanol 'dihydrochloride was prepared from 1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)-2-oxoethyl]cyclopentanol. MS m/z 339 ([M+H]+); HRMS: calcd for C22H30N2O 2.00 HCI, 410.1892; found (ESI), 339.2419. Example 57: 1-[1-(3-chlorophenyl)-2-morpholin-4-ylethyl]cyclohexanol hydrochloride [0267] In an analogous manner to Example 1, step 1 1 -[1-(3-chlorophenyl)-2-morpholin-4-yl-2-oxoethyncyclohexanol was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and morpholine. HRMS: calcd for C18H24CINO3, 337.1445; found (ESI_FT), 338.1521. [0268] In an analogous manner to Example 1, step 2 1-[1-(3-chloropheny!)-2-morpholin-4-ylethyl]cyclohexanol hydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-morpholin-4-yl-2-oxoethyl]cyclohexanol. HRMS: calcd for C18H26CINO2 HCI, 359.1419; found (ESLFT), 324.17137. Example 58: 4-[1 -(3-bromophenyl)-2-piperazin-1 -ylethyl]-1 -methylpiperidin-4-ol dihydrochloride -100- WO 2005/037279 PCT/US20O4/033732 [0269] In an analogous manner to Example 1, step 1 /erf-butyl 4-[(3-bromophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acety)piperazine-1-carboxylate was prepared from (3-bromophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-r) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C23H34BrN3O4 495.1733; found (ESLFT), 496.18082. [0270] In an analogous manner to Example 1, step 2 4-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]-1-methylpiperidin-4-ol dihydrochloride was prepared from tert-butyl 4-[(3-bromophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C18H28BrN3O 3.00 HCI, 489.0716; found (ESI_FT), 382.14952. i Example 59: 1 -methyl-4-[1 -(2-naphthyl)-2-piperazin-1 -ylethyl]piperidin-4-ol dihydrochloride [0271] In an analogous manner to Example 1, step 1 tert-butyl 4-[(4-hydroxy-1-methylpiperidin-4-yl)(2-naphthyl)acetyllpiperazine-1-carboxylate was prepared from (4-hydroxy-1-methylpiperidin-4-yl)(2-naphthyl)acetic acid (Reference Example 1-x) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C27H37N3O4, 467.2784; found (ESLFT), 468.28561. [0272] In an analogous manner to Example 1, step 2 1-methyl-4-[1-(2-naphthyl)-2- piperazin-1-ylethyl]piperidin-4-ol dihydrochloride was prepared from tert-butyl 4-[(4- hydroxy-1 -methylpiperidin-4-yl)(2-naphthyl)acetyl]piperazine-1 -carboxylate. HRMS: calcd for C22H31N3O 3.00 HCI, 461.1767; found (ESLFT), 354.25401. -101- WO 2005/037279 PCT/US2OO4/033732 Example 60: 1 -{1 -(3-bromophenyl)-2-((3-chlorobenzyl)amino]elhyl}cyclohexanol hydjochloride [0273] In an analogous manner to Example 1, step 1 2-(3-bromophenyl)-N-(3-chlorobenzyl)-2-(1-hydroxycyclohexy))acetamide was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 3-chlorobenzylamine. MS (ESI) m/z 436/438/440 ((M+H]+). [0274] !n an analogous manner to Example 1, step 2 1-{1-(3-bromophenyl)-2-[(3-chlorobenzyl)amino]ethyl}cyclohexanol hydrochloride was prepared from 2-(3-bromophenyl)-N-(3-chlorobenzyl)-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z 422/424/426 ([M+H]+); HRMS: calcd for C21H25BrCINO HCI, 457.0575; found (ESI), 422.0873. Example 61: 1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclohexanol hydrochloride [0275] In an analogous manner to Example 1, step 1 N-benzyl-2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)acetamide was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and benzylamine. HRMS: calcd for C21H24BrNO2, 401.0990; found (ESI_FT), 402.10557. -102- \YO 2005/037279 PCT/US2004/033732 [0276] In an analogous manner to Example 1, step 2 1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclohexanol hydrochloride was prepared from A/-benzyl-2-(3-bromdphenyl)-2-(1-hydroxycyclohexyl)acetamide. HRMS: calcd for C21H26BrNO HCI, 423.0965; found (ESI_FT), 388.12785. Example 62: 1-[2-(benzylamino)-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride [0277] In an analogous manner to Example 1, step 1 N-benzyl-2-0- hydroxycyclohexyl)-2-(2-naphthyl)acetamide was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and benzylamine. HRMS: calcd for C25H27NO2, 373.2042; found (ESI_FT), 374.21082. [0278] In an analogous manner to Example 1, step 2 1-[2-(benzylamino)-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride was prepared from N-benzyl-2-(1-hydroxycyclohexyl)-2-(2-naphthyl)acetamide. HRMS: calcd for C25H29NO HCI, 395.2016; found (ESI_FT), 360.23164. Example 63: 1-[1-(2-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0279] In an analogous manner to Example 1, step 1 tert-butyl 40- hydroxycyclohexyl)(2-naphthyl)acetyl1piperazine-1-carboxylate was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-c) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 453 ([M+H]+). -103- W'O 2005/037279 PCT/US2004/033732 [0280] In an analogous manner to Example 1, step 2 1-p-(2-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4(1-hydroxycyclohexyl)(2-naphthyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 339 ([M+H]+); HRMS: calcd for C22H30N2O 2.00 HCI, 410.1892; found (ESI_FT), 339.2426. Example 64: 1-[2-(4-methylpiperazin-1-yl)-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride [0281] In an analogous manner to Example 24, 1-[2-(4-methylpiperazin-1-yl)-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(2-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 63). MS (ESI) m/z 353 ([M+H]+); HRMS: calcd for C23H32N2O 2.00 HCI, 424.2048; found (ESI_FT), 353.25994. Example 65: 2-(3-bromo-4-methoxyphenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol dihydrochloride [0282] In an analogous manner to Example 1, step 1 tert-butyl 4-[2-(3-bromo-4-methoxyphenyl)-3-ethyl-3-hydroxypentanoyl)piperazine-1-carboxylate was prepared from 2-(3-bromo-4-methoxyphenyl)-3-ethyl-3-hydroxypentanoic acid (Reference Example 1-y) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 499/501 ([M+H]+); HRMS: calcd for C23H35BrN2O=, 498.1729; found (ESI), 499.1793. -104- WO 2005/037279 PCT/US2004/033732 [0283] In an analogous manner to Example 1, step 2 2-(3-bromo-4-methoxyphenyl)-3-ethyl-1-(4-methylpiperazin-1-yl)pentan-3-ol dihydrochloride was prepared from tert-butyl 4-[2-(3-bromo-4-methoxyphenyl)-3-ethyl-3-hydroxypentanoyl]piperazine-1-carboxylate. MS m/z 385/387 ([M+H]+); HRMS: calcd for C18H29BrN2O2 2.00 HCI, 456.0946; found (ESI), 385.1494. Example 66: 2-(3-bromo-4-methoxyphenyl)-3-ethyl-1-(4-methylpiperazin-1-yl)pentan-3-ol dihydrochloride [0284] In an analogous manner to Example 24, 2-(3-bromo-4-methoxyphenyl)-3-ethyl-1-(4-methylpiperazin-1-yl)pentan-3-ol dihydrochloride was prepared from 2-(3-bromo-4-methoxyphenyl)-3-ethyl-1-(4-methylpiperazin-1-yl)pentan-3-ol (see Example 65). MS (ESI) m/z 399/401 ([M+H]+); HRMS: calcd for C19H31BrN2O2 • 2.00 HCI, 470.1102; found (ESI), 399.1632. Example 67: 1-[1-(3-chlorophenyl)-2-(cyclohexylamino)ethyl]cyclohexanol hydrochloride [0285] In an analogous manner to Example 1, step 1 2-(3-chlorophenyl)-N-cyclohexyl-2-(1-hydroxycyclohexyl)acetamide was prepared from (3-chlorophenyl)0- -105- WO 2005/037279 PCT/US2004/033732 hydroxycyclohexyl)acetic acid (Reference Example 1-a) and cyclohexylamine. MS (ESI) m/z 350/352 ([M+H]+). [0286] In an analogous manner to Example 1, step 2 1-[1-(3-chlorophenyl)-2-(cyclohexylamino)ethyljcyclohexanol hydrochloride was prepared from 2-(3-chlorophenyl)-N-cyclohexyl-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z 336/338 ([M+H]+); HRMS: calcd for C20H3oCINO HCI, 371.1783; found (ESI), 336.206. Example 68: 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclobutanol dihydrochloride [0287] In an analogous manner to Example 1, step 1 tert-butyl 4-f0- hydroxycyclobutyl)(1-naphthyl)acetyl]piperazine-1 -carboxylate was prepared from (1-hydroxycyclobutyl)(1-naphthyl)acetic acid (Reference Example 1-o) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z425 ([M+H]+). [0288] In an analogous manner to Example 1, step 2 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclobutanol dihydrochloride was prepared from tert-butyl 4-[(1-hydroxycyclobutyl)(1-naphthyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 311 ([M+H]+); HRMS: calcd for C2oH26N2O 2.00 HCI, 382.1579; found (ESI), 311.2127. Example 69: 1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclobutanol dihydrochloride -106- \\O 2005/037279 PCT/US2004/033732 [0289] In an analogous manner to Example 24, 1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclobutanol dihydrochloride was prepared from 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclobutanol (see Example 68). MS (ES) m/z 325.3 ([M+H]+); HRMS: calcd forC21H28N2O 2.00 HCI, 396.1735; found (ESI), 325.2278. Example 70: 1 -{1 -[4-(benzyloxy)phenyl]-2-piperazin-1 -ylethyl}cyclobutanol dihydrochloride [0290] In an analogous manner to Example 1, step 1 tert-butyl 4-[[4- (benzyloxy)phenyl1(1-hydroxycyclobutyl)acetyl]piperazine-1-carboxylate was prepared from (4-benzyloxyphenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-z) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 481 ([M+H]+); HRMS: calcd for C25H36N2O5, 480.2624; found (ESI), 481.2716. [0291] In an analogous manner to Example 1, step 2 1-{1-[4-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol dihydrochloride was prepared from tert-butyl 4-[[4-(benzyloxy)phenyl](1-hydroxycyclobutyl)acetyl]piperazine-1 -carboxylate. HRMS: calcd for C23H3oN202 2.00 HCI, 438.1841; found (ESI), 367.2389. Example 71: 1-[1-[4-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclobutanol dihydrochloride -107- WO 20O5/037279 PCT/US2OO4/033732 [0292] In an analogous manner to Example 24, 1-[1-(4-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclobutanol dihydrochloride was prepared from 1-{1-[4-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol (see Example 70). HRMS: calcd for C24H32N2O2 2.00 HCI, 452.1997; found (ESI), 381.2526. Example 72: 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]decahydronaphthalen-1-ol dihydrochloride [0293] In an analogous manner to Example 1, step 1 tert-buryl 4-[1-(3-chlorophenylphenyl)0-hydroxyl)ccahydronapthyl)acetyllpiperazine-1-carboxylate was prepared from (3-chlorophenyl)(1-hydroxydocahydronapthyl)acetic acid (Reference Example 1-aa) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 491/493 ([M+H]+). [0294] In an analogous manner to Example 1, step 2 1-[1-(3-chlorophenyl)-2- piperazin-1-ylethyl]decahydronaphthalen-1-ol dihydrochloride war, prepared from /erf- butyl 4-[ 1 -(3-chlorophenylphenyl)( 1 -hydroxydecahydronapthyl)acetyl]piperazine-1 - carboxylate. MS (ES) m/z 377.3 ([M+H]+); HRMS: calcd for C22H33CIN2O 2.00 HCI, 448.1815; found (ESI). 377.2351. 108- WO 2005/037279 PCT/US2004/033732 Example 73: 1-[1-(3-bromo-4-methoxyphonyl)-2-(4-methylpiperazin-1-yl)ethyl]-4-tert-butylcyclohexanol dihydrochloride [0295] In an analogous manner to Example 1, step 1 1-[1-(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazin-1-yl)-2-oxoethyll-4-tert-butylcyc1ohexanol was prepared from (3-bromo-4-methoxyphenyl)(4-tert-butyl-1 -hydroxycyclohexyl)acetic acid (Reference Example 1-bb) and N-methylpiperazine. MS (ESI) m/z481/483 ([M+H]+). [0296] In an analogous manner to Example 1, step 2 1 -[1 -(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazin-1-yl)ethyl]-4-tert-butylcyclohexanol dihydrochloride was prepared from /erf-butyl 1 -[1 -(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazin-1 -yl)-2-oxoethyl]-4-tert-butylcyclohexanol. MS (ESI) m/z 467/469 ([M+H]+); HRMS: calcd for C24H39BrN2O2 • 2.00 HCI, 538.1728; found (ESI), 467.2258. Example 74: 2-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]decahydronaphthalen-2-ol dihydrochloride -109- WO 2005/037279 PCT/US2004/033732 [0297] In an analogous manner to Example 1, step 1 tort-butyl 4-[1 -(3-chlorpphenylphenyl)(2-hydroxydecahydronapthyl)acetv!lpiperazine-1-carboxylate was prepared from (3-chlorophenyl)(2-hydroxydecahydronapthyl)acetic acid (Reference Example 1-cc) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 491/493 ([M+H]+). [0298] In an analogous manner to Example 1, step 2 2-[1-(3-chlorophenyl)-2- piperazin-1-ylethyl]decahydronaphthalen-2-ol dihydrochloride was prepared from tert- butyl 4-[1 -(3-chlorophenylphenyl)(2-hydroxydecahydronapthyl)acetyl]piperazine-1 - carboxylate. MS (ESI) m/z 377 ([M+H]+); HRMS: calcd for C22H33CIN2O 2.00 HCI, 448.1815; found (ESI), 377.2346. Example 75: 1-0-(3,4-dichlorophenyl)-2-{[4-(trifluorornethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride [0299] In an analogous manner to Example 1, step 1 2-(3,4-dichlorophenyl)-2-0 -hydroxycyclohexyl)-N-[4-(trifluoromethyl)benzyl]acetamide was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneaceticacid (Reference Example 1-d) and 4-trifluoromethylbenzylamine. MS (ESI) m/z460/462/464 ([M+H]f). [0300] In an analogous manner to Example 1, step 2 1-0-(3,4-dichlorophenyl)-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride was prepared from 2-(3,4-dichlorophenyl)-2-(1-hydroxycyclohexyl)-N-[4-(trifluoromethyl)benzyl]acetamide. MS (ESI) m/z 446/448/450 ([M+H]+); HRMS: calcd for C22H24Cl2[3NO HCI, 481.0954; found (ESI), 446.1232; Anal. Calcd for C22H24CI2[3NO HCI: C, 54.73; H, 5.22; N, 2.90. Found: C, 54.69; H, 4.99; N, 2.78. -110- WO 2005/037279 PCT/US2004/033732 Example 76: 4-tert-buryl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0301] In an analogous manner to Example 1, step 1 tert-butyl 4-[(4-tert-butyl-1-hydroxycyclohexyl)(1-naphthyl)acetyl)piperazine-1-carboxylate was prepared from (4-tert-butyl-1-hydroxycyclohexyl)(1-naphthyl)acetic acid (Reference Example 1-dd) and rert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 509 ([M+H]+); HRMS: calcd for C31H44N2O4, 508.3301; found (ESI), 509.3354. [0302] In an analogous manner to Example 1, stop 2 4-tert-butyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[(4-tert-butyl-1-hydroxycyclohexyl)(1-naphthyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 395 ([M+H]+); HRMS: calcd for C26H38N2O 2.00 HCI, 466.2518; found (ESI), 395.3055. Example 77: 4-[1 -(3-chloropheny!)-2-piperazin-1 -ylethyl]tetrahydro-2H-pyran-4-ol dihydrochloride [0303] In an analogous manner to Example 1, step 1 /erf-butyl 4-[(3-chlorophenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetyl]piperazine-1-carboxylate was prepared from (3-chlorophenyl)(4-hydroxytetrahydro-2fV-pyran-4-y!)acetic acid (Reference Example 1-ee) -111- WO 2005/037279 PCT/US2OO4/033732 and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 439/441 ([M+H]+); HRMS: calcd for C22H31CIN2O5, 438.1921; found (ESI_FT), 439.19884. [0304] In an analogous manner to Example 1, step 2 4-[1-(3-chlorophenyl)-2- piperazin-1-ylethyl]tetrahydro-2H-pyran-4-ol dihydrochloride was prepared from tert- butyl 4-[(3-chlorophenyl)(4-hydroxytctrahydro-2H-pyran-4-yl)acetyl]piperazine-1- carboxylate. MS (ESI) m/z 325/327 ((M+H]+); HRMS: calcd for C17H25CIN2O2 2.00 HCI, 396.1138; found (ESI..FT), 325.16764. Example 78: 4-[1 -(3-chlorophenyl)-2-(4-methylpiperazin-1 -yl)ethyl]tetrahydro-2H-pyran-4-ol dihydrochloride [0305] In an analogous manner to Example 24, 4-[1-(3-chlorophenyl)-2-(4- methylpipprazin-1-y!)ethy!]tetrahydro-2H-pyran-4-o! dihydrochlcride was prepared from 4-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]tetrahydro-2H-pyran-4-ol (see Example 77). MS (ESI) m/z 339 ([M+H]+); HRMS: calcd for C18H27CIN2O2 • 2.00 HCI, 410.1295; found (ESI), 339.1844. Example 79: 1 -[1 -(3-bromophenyl)-2-(4-methylpiperazin-1 -yl)ethyl]-4-tert-butylcyclohexanol dihydrochloride -112- WO 2005/037279 PCT/US2004/033732 [0306] In an analogous manner to Example 1, stop 1 1 -[ 1 -(3-bromophenyl)-2-(4-methytoiperazin-1 -yl)-2-oxoothyl]-4-tert-butylcyclohexanol was prepared from (3-bromophenyl)(4-tert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-ff) and N-methylpipcrazine. MS (ESI) m/z451/453 ([M+H]4). [0307] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]-4-tert-butylcyclohexanol dihydrochloride was prepared from 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)-2-oxoethyl]-4-tert-butylcyclohexanol. MS (ESI) m/z 437/439 ([M+H]+); HRMS: calcd for C23H37BrN2O • 2.00 HCI, 508.1623; found (ESI), 437.2154. Example 80: 1-{1-(3,4-dichlorophenyl)-2-[(4-fluorobenzyl)amino]ethyl}cyclohexanol hydrochloride [0308] In an analogous manner to Example 1, step 1 2-(3.4-dichlorophenyl)-N-(4-fluorobenzyl)-2-(1-hydroxycyclohexyl)acetamide was prepared from 3,4-dichloro-alpha-(i-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and 4-fluorobenzylamine. MS (ESI) m/z410/412/414 ([M+H]+). [0309] In an analogous manner to Example 1, step 2 1-{1-(3,4-dichlorophenyl)-2-[(4-fluorobenzyl)amino]ethyl}cyclohexanol hydrochloride was prepared from 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z 396/398/400 ([M+H]+); HRMS: calcd for C21H24CI2FNO HCI, 431.0986; found (ESI), 396.1277. Example 81: 4-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]heptan-4-ol dihydrochloride -113- wO 2005/037279 PCT/US2004/033732 [0310] In an analogous manner to Example 1, step 1 tert-butyl 4-[2-(3-bromophenyl)-3-hydroxy-3-propylhexanoyl)piperazine-1-carboxylate was prepared from 2-(3-bromophenyl)-3-hydroxy-3-propylhexanoic acid (Reference Example 1-gg) and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z497.2 ([M+H]*). [0311] in an analogous manner to Example 1, step 2 4-[1-(3-bromophenyl)-2-pipsrazin-1-y!ethy!]heptan-4-ol dihydrochloride was prepared from tert-butyl 4-[2-(3-bromophenyl)-3-hydroxy-3-propylhexanoyl]piperazine-1-carboxylate. MS (ES) m/z 383.2 ([M+H]+); HRMS: calcd for Ci9H31BrN2O • 2.00 HCI, 454.1153; found (ESI), 383.1705. Example 82: 4-[1 -(3-bromophenyl)-2-(4-methylpiperazin-1 -y!)ethyl]heptan-4-ol dihydrochloride [0312] In an analogous manner to Example 24, 4-[1-(3-bromophenyl)-2-(4- methylpiperazin-1-yl)ethyl]heptan-4-ol dihydrochloride was prepared from 4-[1-(3- bromophenyl)-2-piperazin-1-ylethyl]heptan-4-ol (see Example 81). MS (ES) m/z 397.2 ([M+H]+); HRMS: calcd for C2oH33BrN20 2.00 HCI, 468.1310; found (ESI), 397.1865. Example 83: 1-[1-(3,4-dichlorophenyl)-2-morpholin-4-ylethyl]cyclobutanol hydrochloride -114- WO 2005/037279 PCT/US2OO4/033732 [0313] In an analogous manner to Example 1, step 1 1 -[ 1 -(3.4-dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]cyclobutanol was prepared from (3,4-dichlorophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-p) and morpholine. HRMS: calcd for C.6H19CI2NO3, 343.0742; found (ESI_FT), 344.08102. [0314] !n an analogous manner to Example 1, step 2 1-[1-(3,4-dichioroprieny!)-2- morpholin-4-ylethyl]cyclobutanol hydrochloride was prepared from 1-[1-(3,4- dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]cyclobutanol. HRMS: calcd for C16H21CI2NO2 HCI, 365.0716; found (ESLFT), 330.10064. Example 84; 1-[1-(3-bromo-4-methoxyphenyl)-2-piperazin-1-ylethyl]-4-tert-butylcyclohexanol dihydrochloride [0315] In an analogous manner to Example 1, step 1 /erf-butyl 4-[(3-bromo-4-methoxyphenyl)(4-tert-butyl-1 -hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate was prepared from (3-bromo-4-methoxyphenyl)(4-tert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-bb) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 567/569 ([M+H]+); HRMS: calcd for C28H43BrN2O5, 566.2355; found (ESI), 567.2435. -1 15- WO 2005/037279 PCT/US2OO4/033732 [0316] In an analogous manner to Example 1, step 2 1 -[1 -(3-bromo-4-methoxyphenyl)-2-.p>oerazin-1-ylethyl]-4-tert-butylcyclohexanol dihydrochlonde was prepared from ten-butyl 4-[(3-bromo-4-methoxyphenyl)(4-tert-butyl-1 -hydroxycyclohexyl)acetyl]piperazme-1-carboxylate. MS (ESI) m/z 453'455 ([M+H]+); HRMS: calcd for C23H37BrN2O2 2.00 HCI. 524.1572. found (ESI), 453 2119. Example 85. 1-[1-(3-chlorophenyl)-2-piperidin-1-ylethyl]cyclohexanol hydrochloride [0317] In an analogous manner to Example 1, step 1 .1-[1_-(3-chlorophenyl1-2-oxo-2-piperidin-1-ylethyl]cyclohexanol was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and piperidine. HRMS: calcd for C19H26ClNO2. 335.1652; found (ESI_FT), 336.17194. [0318] In an analogous manner to Example 1, step 2 1-[1-(3-chlorophenyl)-2-piperidin-1-ylethyl]cyclohexanol hydrochloride was prepared from 1-0-(3-chlorophenyl)-2-oxo-2- piperidin-1-ylethyl]cyclonexanol HRMS caled for CHCINO HCI 357,1626:found (ESLFT). 322.19304 Example 86: 2-(3-chlorophenyl)-1.1 -dicyclopropyl-3-(4-mcthylpiperazin-1 -yl)propan-1 -ol dihydrochloride [0319] In an analogous manner to Example 1, step 1 tert-butyl 4-(2-(3-chlorophcnyl) (3.3-dicyclopropyl-3-hydroxypropyl)acetyl)piperazine-1-carboxylate was prepared from -116- WO 2005/037279 PCT/US2OO4/033732 2-(3-chlorophenyl)-3,3-dicyclopropyl-3-hydroxypropanoic acid (Reference Example 1-hh) and N-methylpiperazine. MS (ESI) m/z 363 ([M+H]+). [0320] In an analogous manner to Example 1, step 2 2-(3-chlorophenyl)-1,1-dicyclopropyl-3-(4-methylpiperazin-1-yl)propan-1-ol dihydrochloride was prepared from rert-butyl 4-[2-(3-chlorophenyl) (3,3-dicyclopropyl-3-hydroxypropyl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z 349.2037 ([M+H]+); HRMS: calcd for C2oH2oCIN20 2.00 HCI, 420.1502; found (ESI), 349.2037. Example 87: 1 -[1 -(3-bromophenyl)-2-piperazin-1 -ylethyl]-3,3,5,5-tetramethylcyclohexanol dihydrochloride [0321] In an analogous manner to Example 1, step 1 /erf-butyl 4-[(3-bromophenyl)0-hydroxv-3.3.5.5-tetramethylcyclohexyl)acetynpiperazine-1-carboxylate was prepared from (3-bromophenyl)(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetic acid (Reference Example 1-ii) and tert-butyl 1-piperazinecarboxylate. [0322] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyt)-2-piperazin-1-ylethyl]-3,3,5,5-tetramethylcyclohexanol dihydrochloride was prepared from tert-butyl 4-[(3-bromophenyl)(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetynpiperazine-1-carboxyla1e. MS (ES) m/z 423.2 ([M+Hf); HRMS: calcd for C22H35BrN2O, 422.1933; found (ESI), 423.2015. Example 88: 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]-3,3,5,5-tetramethylcyclohexanol dihydrochloride -117- WO 2005/037279 PCT/US2004/033732 [0323] In an analogous manner to Example 24, 1-[1-(3-bromcphenyl)-2-(4- methylpiperazin-1 -yl)ethyl]-3,3,5,5-tetramethylcyclohexanol dihydrochloride was prepared from 1-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]-3,3,5,5- tctramethylcyclohexanol (see Example 87). MS (ES) m/z 437.3 ([M+H]+); HRMS: calcd for C23H37BrN2O 2.00 HCI, 508.1623; found (ESI), 437.2162. Example 89: 3-ethyl-1 -(4-methylpiperazin-1 -yl)-2-(1 -naphthyl)pentan-3-ol dihydrochloride [0324] In an analogous manner to Example 24, 3-ethyl-1 -(4-methylpiperazin-1 -yl)-2-(1 -naphthyl)pentan-3-ol dihydrochloride was prepared from 3-ethyl-2-(1-naphthyl)-1-piperazin-1-ylpentan-3-ol (see Example 53). MS (ESI) m/z 341 ([M+H]+); HRMS: calcd for C22H32N2O 2.00 HCI, 412.2048; found (ESI), 341.2583. Example 90: 1-0-(3-bromophenyl)-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride -118- WO 2005/037279 PCT/US2OO4/033732 [0325] In an analogous manner to Example 1, step 1 2-(3-bromophenyl)-2-0 -hydroxycyclohexyl)-N-[4-(trifluoromethynbenzynacetamide was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-trifluoromethylbenzylamine. MS (ESI) m/z 470/472 ([M+H]+). [0326] In an analogous manner to Example 1, step 2 1-0-(3-bromophenyl)-2-{[4- (trif!uoromethyl)benzyl]amino}ethy!)cyc!ohexanol hydrochloride was prepared from 2-(3- bromophenyl)-2-(1-hydroxycyclohexyl)-N-[4-(trifluoromethyl)benzyl]acetamide. MS (ESI) m/z 456/458 ([M+H]+); HRMS: calcd for C22H25Br[3NO HCI, 491.0838; found (ESI), 456.1147. Example 91: 4-ethyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0327] In an analogous manner to Example 1, step 1 tort-butyl 4-[1-(1-naphthyl)- (4-ethyl-1 -hydroxycyclohoxyl)acetynpiperazine-i-carboxylate was prepared from (4-ethyl-1-hydroxycyclohexyl) -(1-naphthyl) acetic acid (Reference Example 1-jj) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 481 ([M+H]+); [0328] In an analogous manner to Example 1, step 2 4-ethyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[1-0- -119- WO 2005/037279 PCT/US2004/033732 naphthyl)- (4-ethyl-1-hydroxycyclohexyl)acetyl]pipcrazine-1-carboxylate. MS (ESI) m/z 367 ([M+H]+); HRMS: calcd for C24H34N2O 2.00 HCI. 438.2205; found (ESI), 367.2749. Example 92: 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclobutanol dihydrochloride [0329] In an analogous manner to Example 24, 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclobutanol dihydrochloride was prepared from 1-{2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclobutanol (see Example 46). HRMS: calcd for C18H25[3N2O2 2.00 HCI, 430.1402; found (ESI), 359.1965. Example 93: 4-tert-butyl-1 -[1 -(3-chlorophenyl)-2-piperazin-1 -ylethy!]cyclohGxanol dihydrochloride [0330] In an analogous manner to Example 1, step 1 tert-butyl 4-[(4-tert-butyl-1-hydroxycyclohexyl)(3-chlorophenyl)acetyl1pipera7ine-1-carboxylate was prepared from (3-chlorophenyl)(4-tert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-kk) and /erf-butyl 1-piperazinecarboxylate. MS (ES) m/z 493.4 ([M+H]+). [0331] In an analogous manner to Example 1, step 2 4-tert-butyl-1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[(4- -120- WO 2005/037279 I'CT/US200.|/«33732 tert-butyl-1-hydroxycyclohoxyl)(3-chlorophenyl)acetyl]piperazine-1-carboxylato. MS (ESI) m/z 379 ([M+H]+); HRMS: calcd for C22H35CIN2O, 378.2438; found (ESI), 379.2513. Example 94: 2-(3-chlorophenyl)-3-ethyl-1-(4-methylpiperazin-1-yl)pentan-3-ol dihydrochloride [0332] In an analogous manner to Example 24, 2-(3-chlorophenyl)-3-ethyl-1-(4-methylpiperazin-1-y!)pentan-3-ol dihydrochloride was prepared from 2-(3-ch!orophenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol (see Example 52). (ESI) m/z 325/327 ([M+H]+); HRMS: calcd for C18H29CIN2O 2.00 HCI, 396.1502; found (ESI), 325.2032. Example 95: 1-[1-(3-bromophenyl)-2-morpholin-4-ylethyl]cyclobutanol hydrochloride [0333] In an analogous manner to Example 1, step 1 1-[1-(3-bromophenyl)-2-morpholin-4-yl-2-oxoethyl]cyclobutanol was prepared from (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and morpholine. HRMS: calcd for C16H2oBrN03, 353.0627; found (ESI_FT), 354.06919. [0334] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2-morpholin-4-ylethyl]cyclobutanol hydrochloride was prepared from tert-butyl 4-[(A-tert- -121- WO 2005/037279 PCT/US2004/033732 butyl-1-hydroxycyclohexyl)(3-chlorophenyl)acetyl]piperazine-1-carboxylate. HRMS: calcd-ior C16H22BrNO2 HCI, 375.0601; found (ESI_FT), 340.08898. Example 96: 1 -[1 -(3-bromophenyl)-2-piperazin-1 -ylethyl]-4-tert-butylcyclohexanol dihydrochloride [0335] In an analogous manner to Example 1, step 1 tert-butyl 4-[(3-bromophenyl)(4-tert-butyl-1-hydroxycyclohexyl)acetyflpiperazine-1-carboxylate was prepared from (3-brornophenyl)(4-tert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-ff) and /erf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 537/539 ([M+H]+); HRMS: calcd for C27H41BrN2O4, 536.2250; found (ESI), 537.2324. [0336] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2- piperazin-1-y!ethy!]-4-tert-butylcyc!ohexano! dihydrcchlcrids was prepared from tsrt- butyl 4-[(3-bromophenyl)(4-tert-butyl-1-hydroxycyclohexyl)acetyl]piperazine-1- carboxylate. MS (ESI) m/z 423/425 ([M+H]+); HRMS: calcd for C22H35BrN2O 2.00 HCI, 494.1466; found (ESI), 423.1994. Example 97: 4-methyl-1 -[1 -(1 -naphthyl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride -122- WO 2005/037279 PCT/l;S20»4/033732 [0337] In an analogous manner to Example 1, step 1 /erf-butyl 4-[1-(1-naphthyl)- (4-mothyl-1 -hydroxvcyclohexvhacGtyl]piporazine-i -carboxylate was prepared from (4-methy/-'1-hydroxycyclohexyl) -0-naphlhyl) acetic acid (Reference Example 1-11) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 467 ([M+H]+). [0338] In an analogous manner to Example 1, step 2 4-methyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[1-(1-naphthyl)- (4-methyl-1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 353 ([M+H]+); HRMS: calcd for C23H32N2O • 2.00 HCI, 424.2048; found (ESI), 353.2599. Example 98: 1 -{1 -(3-bromophenyl)-2-[(4-fluorobenzyl)amino]ethyl}cyclohexanol hydrochloride [0339] In an analogous manner to Example 1, step 1 2-(3-bromophenyl)-N-(4-fluorobenzyl)-2-(1-hydroxycyclohexyl)acetamide was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-fluorobenzylamine. MS (ESI) m/z 420/422 ([M+H]+)- [0340] In an analogous manner to Example 1, step 2 1-{1-(3-bromophenyl)-2-[(4-fluorobenzyl)amino]ethyl}cyclohexanol hydrochloride was prepared from 2-(3-bromophenyl)-N-(4-fluorobenzyl)-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z 406 ([M+H]+); MS (ESI) m/z 408 ([M-H]+); HRMS: calcd for C21H25BrFNO HCI, 441.0870; found (ESI), 406.1173. Example 99: 1-[1-(3-bromophenyl)-2-morpholin-4-ylethyl]cyclohexanol hydrochloride -123- \\0 2005/037279 PCT/US2004/033732 (0341 ] In an analogous manner to Example 1, step 1 1 -[1 -(3-bromophenyl)-2-morpholin-4-yl-2-oxoethyl|cyclohexanol was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and morpholine. HRMS: calcd forC18H24BrNO3, 381.0940; found (ESI_FT), 382.10032. [03^2] !n an analogous manner to Example 1, step 2 1-i1-(3-bromophenyl)-2-morpholin-4-ylethyl]cyclohexanol , hydrochloride was prepared from 1-[1-(3-bromophenyl)-2-morpholin-4-yl-2-oxoethyl]cyclohexanol. HRMS: calcd for C18H25BrNO2 HCI, 403.0914; found (ESLFT), 368.12137. Example 100: 4-tert-butyl-1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride [0343] In an analogous manner to Example 24, 4-tert-butyl-1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from 4-tert-butyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 76). MS (ESI) m/z 409 ([M+H]+); HRMS: calcd for C27H40N2O • 2.00 HCI, 480.2674; found (ESI), 409.3207. Example 101: 4-tert-butyl-1-[1-(3-chlorophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride -124- WO 2005/037279 PCT/US2004/O33732 [0344] In an analogous manner to Example 24, 4-tert-butyl-1-[1-(3-chlorophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride was prepared from 4-tert-butyl-1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 93). MS (ESI) m/z 393 ([M+H]+); HRMS: calcd for C23H37CIN2O 2.00 HCI, 464.2128; found (ESI), 393.2673. Example 102: 1 -methyl-4-[2-morpholin-4-yl-1 -(2-naphthy1)ethyl]piperidin-4-ol hydrochioride [0345] In an analogous manner to Example 1, step 1 1 -methyl-4-[2-morpholin-4-yl-1 -(2-naphthyl)-2-oxoethynpiperidin-4-ol was prepared from (4-hydroxy-1-methylpiperidin-4-yl)(2-naphthyl)acetic acid (Reference Example 1-x) and morpholine HRMS: calcd for C22H28N2O3, 368.2100; found (ES!_FT), 369.21652. [0346] In an analogous manner to Example 1, step 2 1-methyl-4-[2-morpholin-4-yl-1-(2-naphthyl)ethyl]piperidin-4-ol hydrochioride was prepared from 1-methyl-4-[2-morpholin-4-yl-1-(2-naphthyl)-2-oxoethyl]piperidin-4-ol. HRMS: calcd for C22H30N2O+ ' 2.00 HCI, 426.1841; found (ESI_FT), 355.23761. Example 103: 4-[1 -(3-brcmophenyl)-2-piperazin-1 -yle!hyl]tetrahydro-2H-pyran-4-ol dihydrochloride -125- W'O 2005/037279 PCT/US2004/033732 [0347] In an analogous manner to Example 1, step 1 ter-butyl 4-[(3-bromophenyl)(4-hydroxytetrahydro-2H-pvran-4-yl)acetyl]piperazine-1-carboxylate was prepared from (3-bromophenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetic acid (Reference Example 1-mm) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z483/485 ([M+H]+); HRMS: calcd for C22H31BrN2O5, 482.1416; found (ESI), 483.1508. [0348] In an analogous manner to Example 1, step 2 4-[1-(3-brornophcr:y!)-2- piperazin-1-ylethyl]tetrahydro-2H-pyran-4-ol dihydrochloride was prepared from tcrt- butyl 4-[(3-bromophenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetyl]piperazine-1- carboxylate. MS (ESI) m/z 369/371 ([M+H]+); HRMS: calcd for C17H25BrN2O2 ' 2.00 HCI, 440.0633; found (ESI), 369.1166. . Example 104: 1 -{1 -[3-(benzyloxy)phenyl]-2-piperazin-1 -ylethyl}cyclohexano! dihydrochloride [0349] In an analogous manner to Example 1, step 1 tert-butyl 4-f[3-(benzyloxy)phenyn(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate was prepared from (3-benzyloxyphenyl)(4-hydroxycyclohexyl)acetic acid (Reference Example 1-nn) -126- WO 2005/037279 PCT/US2OO4/033732 and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 509 ([M+H]+); HRMS: calcd for C30H40N2O=, 508.2937; found (ESI), 509.2997. [0350] In an analogous manner to Example 1, step 2 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride was prepared from tert-butyl 4-[[3-(benzyloxy)phenyl](1-hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate. HRMS: calcd for C25H34N2O2 2.00 HCI, 466.2154; found (ESI), 395.2676. Example 105: 1-0-(3-chlorophenyl)-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride [0351] In an analogous manner to Example 1, step 1 2-(3-chlorophenyl)-2-(1-hydroxycyclohexyl)-N-[4-(trifluoromethyl)benzyl]acetamide was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and 4-trifluoromethylbenzylamino. MS (ESI) m/z 426/428 ([M+H]+). [0352] In an analogous manner to Example 1, step 2 1-0-(3-chlorophenyl)-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride was prepared from 2-(3-chlorophenyl)-2-(1-hydroxycyclohexyl)-N-[4-(trifluoromethyl)benzyl]acetamide. MS (ESI) m/z [M+H]+ (412/414). Example 106: 1-[2-morpholin-4-yl-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride -127- WO 2005/037279 PCT7US2004/033732 [0353] In an analogous manner to Example 1, step 1 1 -[2-morpholin-4-yl-1 -12-naphthyl)-2-oxoethyl]cyclohexanol was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and morpholine. HRMS: calcd for C22H27NO3, 353.1991; found (ESI_FT), 354.20523. [0354] In an analogous manner to Example 1, step 2 1-[2-morpholin-4-yl-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride was prepared from 1-[2-morpholin-4-yl-1-(2-naphthyl)-2-oxoethyl]cyclohexanol. HRMS: calcd for C22H29NO2 HCI, 375.1965; found (ESI_FT), 340.2256. Example 107: 2-[1 -(3-bromophenyl)-2-piperazin-1 -ylethyl]adamantan-2-ol dihydrochloride [0355] In an analogous manner to Example 1, step 1 tert-butyl 4-rC3-bromopheny!)(2-hydroxy-2-adamantyl)acetyl]piperazine-1-carboxylate was prepared from (3-bromophenyl)(2-hydroxy-2-adamantyl)acctic acid (Reference Example 1-oo) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 533/535 ([M+H]+). [0356] In an analogous manner to Example 1, step 2 2-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]adamantan-2-ol dihydrochloride was prepared from tert-butyl 4-[(3-bromophenyl)(2-hydroxy-2-adamantyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z -128- WO 2005/037279 PCT/US2004/033732 419/421 ([M+H]+); HRMS: calcd for C22H31BrN2O 2.00 HCI, 490.1153; found (ESI), 419.16.82. Example 108: 1-[1-[3-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride [0357] In an analogous manner to Example 24, 1-[1-[3-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride was prepared from 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol (see Example 104). HRMS: calcd for C25H36N2O2 2.00 HCI, 480.2310; found (ESI), 409.2838. Example 109: 1-[2-morpholin-4-yl-1-(2-naphthyl)ethyl]cyclobutanol hydrochloride [0358] In an analogous manner to Example 1, step 1 1 -|2-morpholin-4-yl-1 -(2-naphthyl)-2-oxoethyl]cyclobutanol was prepared from (1-hydroxycyclobutyl)(2-naphthyl)acetic acid (Reference Example 1-c) and morpholine. HRMS: calcd for C20H23NO=, 325.1678; found (ESI._FT), 326.17435. [0359] In an analogous manner to Example 1, step 2 1-[2-morpholin-4-yl-1-(2-naphthyl)ethyl]cyclobutanol hydrochloride was prepared from 1-[2-rnorpholin-4-yl-1-(2- -129- WO 2005/037279 PCT/US2OO4/0337J2 naphthyl)-2-oxoethyl]cyclobutanol. HRMS: calcd for C20H25NO2 HCI, 347.1652; found (ESlFT), 312.19602. Example 110: 4-[1-(3-bromo-4-methoxyphenyl)-2-piperazin-1-ylethyl]tetrahydro-2H-pyran-4-ol dihydrochloride [0360] In an analogous manner to Example 1, step 1 tert-butyl 4-[(3-bromo-4-methoxyphenyl)(4-hydroxytetrahydro-2H-pvran-4-yl]acetyllpiperazine-1-carboxylate was prepared from (3-bromo-4-methoxyphenyl)(4-hydroxytetrahydro-2/-/-pyran-4-yl)aceiic acid (Reference Example 1-pp) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 513/515 ([M+H]+); HRMS: calcd for C23H33BrN2O6 512.1522; found (ESI), 513.16. [0361 ] in an analogous manner to Example 1, step 2 4-[1 -(3-bromo-4-methoxyphenyl)- 2-piperazin-1-y!ethyl]tetrahydro-2H-pyran-4-ol dihydrochloride was prepared from /erf- butyl 4-[(3-bromo-4-methoxyphenyl)(4-hydroxytetrahydro-2H-pyran-4- yl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 399/401 ([M+H]+); HRMS: calcd for C18H27BrN2O3 2.00 HCI, 470.0739; found (ESI), 399.1266. Example 111: 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylet'nyl}cyclobutanoi dihydrochloride -130- WO 2005/037279 PCT/US2004/033732 [0362] In an analogous manner to Example 1, step 1 tert-butyl 4-[[3-(Benzyloxy)phenyl](1-hydroxycyclobutyl)acetyl]piperazine-1-carboxylate was prepared from (3-benzyloxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-qq) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z481 ([M+H]+); HRMS: calcd for C28H=N2O5, 480.2624; found (ESI), 481.272. [0363] In an analogous manner to Example 1, step 2 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol dihydrochloride was prepared from tert-butyl 4-[[3-(benzyloxy)phenyl](1-hydroxycyclobutyl)acetyl]piperazine-1 -carboxylate. HRMS: calcd for C23H3oN2O= 2.00 HCI, 438.1841; found (ESI), 367.2357. Example 112: 1-[1-(3,4-dichlorophenyl)-2-morpholin-4-ylethyl]cyclohexanol hydrochloride [0364] In an analogous manner to Example 1, step 1 1 -[ 1 -(3.4-dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl1cyclohexanol was prepared from 3,4-dichloro-a!pha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and morpholine. HRMS: calcd for C18H23CI2NO3. 371.1055; found (ESI_FT), 372.11122. -131- WO 2005/037279 PCT/US2004/033732 [0365] In an analogous manner to Example 1, stop 2 1-[1-(3,4-dichlorophenyl)-2- morptiolin-4-ylethyl]cyclohexanol hydrochloride was prepared from 1-[1-(3,4- dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]cyclohexanol. HRMS: calcd for C18H25CI2NO2 HCI, 393.1029; found (ESI_FT), 358.13358. Example 113: 1-[2-[(4-fluorobenzyl)amino]-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride [0366] In an analogous manner to Example 1, step 1 N-(4-fluorobenzyl)-2-(1-hydroxycyclohexyl)-2-(2-naphthyl)acetamide was prepared from (1-hydroxycyclobutyl)(2-naphthyl)acetic acid (Reference Example 1-c) and 4-fluorolbenzylamine. MS (ESI) m/z 372 ([M+H-H2O]+). [0367] In an analogous manner to Example 1, step 2 1-[2-[(4-fluorobenzyl)amino]-1-(2-n3phthy!)eihyljcyc!ohexanoi hydrochioride was prepared from A/-(4-fluorobenzyl)-2-(1-hydroxycyclohexyl)-2-(2-naphthyl)acetamide. MS m/z 378 ([M+H]'); HRMS: calcd for C25H28FNO HCI, 413.1922; found (ESI), 378.2234. Example 114: 4-[1-(3,4-dichlorophenyl)-2-morpholin-4-ylethyl]-1-methylpiperidin-4-o! dihydrochloride -132- WO 2005/037279 PCT/US2004/033732 [0368] In an analogous manner to Example 1, step 1 4-[1 -(3.4-dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]-1-methylpiperidin-4-ol was prepared from (3,4-dichlorophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-i) and morpholine. HRMS: calcd for C18H24Cl2O3, 386.1164; found (ESI._FT), 387.12304. [0369] In an analogous manner to Example 1, step 2 4-[1-(3,4-dichlorophenyl)-2-morpholin-4-ylethyl]-1-methylpiperidin-4-ol dihydrochloride was prepared from 4-[1-(3,4-dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]-1-methylpiperidin-4-ol. HRMS: calcd for C18H26Cl=N2O2 2.00 HCI, 444.0905; found (ESI_FT), 373.14421. Example 115: 1-[1-[3-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclobutanol dihydrochloride [0370] In an analogous manner to Example 24, 1-[1-[3-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclobutano! dihydrochloride was prepared from 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol (see Example 111). HRMS: calcd for C24H32N2O2 2.00 HCI, 452.1997; found (ESI), 381.2524. Example 116: 4-[1-(3-bromophenyl)-2-morpholin-4-ylethyl]-1-methylpiperidin-4-ol dihydrochloride -133- WO 2005/037279 PCT/US2004/033732 [0371] In an analogous manner to Example 1, step 1 4-[1 -(3-bromophenyl)-2-morpholin-4-yl-2-oxoethyl]-1-methylpiperidin-4-ol was prepared from (3-bromophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-r) and morpholine. HRMS: calcd for C18H25BrN2O3. 396.1049; found (ESI_FT), 397.11148. [0372] In an analogous manner to Example 1, step 2 4-[1-(3-bromophenyl)-2-morpholin-4-ylethyl]-1-methylpiperidin-4-ol dihydrochloride was prepared from 4-[1-(3-bromophenyl)-2-morpholin-4-yl-2-oxoethyl]-1-methylpiperidin-4-ol. HRMS: calcd for C18H27BrN2O2 HCI, 418.1023; found (ESI_FT), 383.13261. Example 117: 1-0-(3-chlorophenyl)-2-(4-[(6-methoxy-2-naphthyl)methyl]piperazin-1- yl)ethyl)cyclohexanol dihydrochloride [0373] A solution o[1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) (200 mg, 0.62 mmol) and 6-methoxy-2-napthaldehyde 073 mg, 0.93 mmol) in dichloroethane (4 mL) was treated with sodium trisacetoxyborohydride 095 mg, 0.92 mmol). The reaction was placed on a shaker and where it was stirred for 16 h. The reaction was then washed with a 2 N aqueous solution of hydrochloric acid (2x2 mL), and the organic layer was stored at 25 °C for 16 h. The resulting precipitate was collected, washed with diethyl ether and dried in vacuo to yleld 194 mg (64%) 1-0-(3-chlorophenyl)-2-(4-[(6-methoxy-2-naphthyl)methynpiperazin-1-yl)ethyl)cyclohexanol -134- \YL) 2005/037279 PCT/US2004/O33732 dihydrochloride as a white solid. MS (ESI) m/z493/495 ([M+H]+); HRMS: calcd for C30H37CIN2O2 2.00 HCI, 564.2077; found (ESI_FT), 493.2632. Example 118: 1 -0 -(3-chlorophenyl)-2-[4-fcyclopropylmethyl)piperazin-1 -yl]ethyl}cyclohexanol dihydrochloride [0374] In an analogous manner to Example 117, 1 -0 -(3-chlorophenyl)-2-[4-('cyclopropvimethyl)piperazin-1-yl]ethyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3-ch!orcphenyl)-2-piperazin-1-ylethyl]cyclohexano! (see Example 1) and cyclopropanecarboxaldehyde. MS (ESI) m/z [M+H]+ (377/379); HRMS: calcd for C22H33CIN2O 2.00 HCI, 448.1815; found (ESI), 377.2347. Example 119:1 -0 -(3-chlorophenyl)-2-[4-(cyclohex-3-en-1 -ylmethyl)piperazin-1 - yliethyl}cyclohexanol dihydrochloride -135- WO 2005/037279 PCT/US2004/033732 [0375J In an analogous manner to Example 117, 1-{1-(3-chlorophenyl)-2-[4-(cyclohex-3-en-4ylmethyl)piperazin-1-yl]ethyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3-ch!orophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 3-cyclohexene-1-carboxaldehyde. MS (ESI) m/z [M+H]+ (417/419); HRMS: calcd for C25H37CIN2O 2.00 HCI. 488.2128; found (ESI), 417.2655. Example 120: 6-((4-[2-(3-chlorophenyl)-2-(1-hydroxvcyclohexyl)ethylipiperazin-1 -yl)methyl)tetrahydro-2H-pyran-2-ol dihydrochloride [0376] In an analogous manner to Example 117, 6-((4-[2-(3-chlorophenyl)-2-(1-hydroxycyclohexyl]ethyl]piperazin-1-yl)methyl)tetrahydro-2H-pvran-2-ol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 3,4-dihydro-2H-pyran-2-carboxaldehyde. HRMS: calcd for C24H37ClN2O3 2.00 HCi, 508.2026; found (ESI), 419.2455. Example 121: 1 -{ 1 -(3-chlorophenyl)-2-[4-(3-phenylbutyl)piperazin-1 -yl]ethyl}cyclohexanol dihydrochloride [0377] In an analogous manner to Example 117, 1-0-(3-chlorophenyl)-2-[4-(3-Phenylbutyl)piperazin-1-yl1ethyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperaz:n-1-ylethyl]cyclohexanol (see Example 1) and 3- -136- WO 2005/037279 PCT/US2004/033732 phenylbutyraldehyde. MS (ESI) m/z455/457 ([M+H]+); HRMS: calcd for C28H39CIN2O 2.001HCI, 526.2284; found (ESI_FT), 455.28235. Example 122: 1 -0 -(3-chlorophenyl)-2-[4-(2-phenyleihyl)piperazin-1 -yl]ethyl}cyclohexanol dihydrochloride [0378] in an analogous manner to Example 117, 1 -0 -(3-chlorophenyl)-2-[4-(2-phenylethy!)piperazin-1-yl]othyl)cyciohexanol dihydrochioride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and phenylacetaldehyde. MS (ESI) m/z 427/429 ([M+H]+); HRMS: calcd for C26H35CIN2O 2.00 HCI, 498.1971; found (ESI), 427.2505. Example 123: 1 -{ 1 -(3-chlorophenyl)-2-[4-(3-phenoxvbGnzyl)piperazin-1 -yl]othyl}cyclohcxanol dihydrochloride -137- WO 2005/037279 PCT/US2004/033732 [0379] In an analogous manner to Example 117, 1 -{1 -(3-chlorophenyl)-2-[4-(3-phenaoxybenzynpiperazin-1 -yl]ethyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 3-phenoxybenzaldehyde. MS (ESI) m/z 505/507 ([M+H]+); HRMS: calcd for C31H37CIN2O2 2.00 HCI, 576.2077; found (ESI_.FT), 505.26266. Example 124: 1 -0 -(3-chlorophenyl)-2-[4-(2-naphthylmethyl')piperazin-1 -yl]ethl}cyclohexanol dihydrochloride [0380] In an analogous manner to Example 117, 1-0-(3-chlorophenyl)-2-[4-(2-naphthylmethyl)piperazin-1-yllethyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 2-napthaldehyde. MS (ESI) m/z463/465 ([M+H]+); HRMS: calcd for C29H35CIN2O ' 2.00 HCI, 534.1971; found (ESI), 463.2499. Example 125: 1-0-(3-chlorophenyl)-2-[4-(3-furylmethyl)piperazin-1-yl]thyl}cyclohexanol dihydrochloride [0381 ] In an analogous manner to Example 117, 1 -0 -(3-chlorophenyl)-2-[4-(3-furylmethyl)piperazin-1 -yllethyllcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-y!ethy!]cyc!ohexano! (see Example 1) and 3-furaldehyde. -138- WO 2005/037279 PCT/US2OO4/033732 MS (ESI) m/z[M+H]+ (403/405); HRMS: calcd for C23H31CIN2O2 2.00 HCI, 474.1608; found (ESI), 403.2124. Example 126: 1 -{1 -(3-chlorophenYl)-2-[4-(cyclohexylmethyl)piperazin-1 -vHethyl}cyclohexanol dihydrochloride [0382] In an analogous manner to Example 117, 1 -0 -(3-chlorophenyl)-2-[4-('cyclohexvimethvi')piperazin-1-yl]ethyl)cyclohexanol dihydrochloride was prepared from 1-[1'(3-ch!crcphsnyl)-2-p:perazin-1-ylethy!]cyc!ohexanol (see Example 1) and cyclohexanecarboxaldehyde. MS (ESI) m/z 419/421 ([M+H]+); HRMS: calcd for C25H39CIN2O 2.00 HCI, 490.2284; found (ESI), 419.2815. Example 127: 1 -0 -(3-chlorophenyl)-2-[4-(quinolin-4-ylmethyl)piperazin-1 -yl]ethyl}cyclohexanol dihydrochloride -139- WO 2005/037279 PCT/US2004/033732 [0383] In an analogous manner to Example 117, 1-{1-(3-chlorophenyl)-2-[,4-(guinolin-4-ylmethyl)piperazin-1 -yl]elhyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohoxanol (see Example 1) and 4-quinolinecarboxaldehyde. MS (ESI) m/z 464/466 ((M+H]+); HRMS: calcd for C28H34CIN3O 3.00 HCI, 571.1691; found (ESI_FT), 464.24693. Example 128: 1-0-(3-chlorophenyl)-2-(4-[(5-ethyl-2-furyl)methyl1piperazin-1-yl}elhyl)cyclohexanol dihydrochloride [0384] In an analogous manner to Example 117, 1-0-(3-chlorophenyl)-2-(4-r(5-ethyl-2-furyl)methyl]piperazin-1-yl)ethyl)cyclohexanol dihydrochloride was prepared from 1 -[ 1 -(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 5-ethyl-2-furaldehyde. MS (ESI) m/z [M+H]+ (431/433); HRMS: calcd for C25H35CIN2O2 ' 2.00 HCI, 502.1921; found (ESI), 431.2454. Example 129: 1 -0 -(3-chlorophenyl)-2-[4-(2-phenylpropyl)piperazin-1 -yl]ethyl)cyclohexanol dihydrochloride [0385] In-an analogous manner to Example 117, 1 -0 -(3-chlorophenyl)-2-[4-(2-phenylpropyl)piperazin-1 -yl]ethyl}cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 2- -140- WO 2005/037279 PCT/US2004/O33732 phenylpropionaldehydc. MS (ESI) m/z 441/443 ([M+H]+); HRMS: calcd for C27H37CIN2O 2.00 HCI, 512.2128; found (ESI), 441.2662. Example 130: 1 -[2-[4-0 -benzofuran-2-ylmethyl)piperazin-1 -yl]-1 -(3-chlorophenyl)ethyl]cyclohexanol dihydrochloride [0386] In an analogous manner to Example 117, 1 -[2-[4-0 -benzofuran-2-ylmethyl')piperazin-1 -yl]-1 -(3-chlorophenyl)ethyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3 ch!orcphenyl)-2-piperazin-1-y!ethyljcyclohexanoi (see Example 1) and benzo[B]furan-2-carboxaldehyde. MS (ESI) m/z[M+H]+ (453/455); HRMS: calcd for C27H33CIN2O2 2.00 HCI, 524.1764; found (ESI), 453.2296. Example 131: 1-[2-(4-[4-(benzyloxy)benzyl1piperazin-1-yl)-1-(3-chlorophenyl)ethyncyclohoxanol dihydrochloride -141- WO 20O5/O.57279 PCT/US2O04/033732 [0387] in an analogous manner to Example 117, 1-[2-(4-[4- (bgnzyloxy)benzyl)piperazin-1-yl)-1-(3-chlorophenyl]ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(3-ch!orophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 4-benzyloxybenzaldchyde. MS (ESI) m/z 519/521 ([M+H]+); HRMS: calcd for C32H39CIN2O2 2.00 HCI, 590.2234; found (ESI_FT), 519.27544. Example 132: 1 -0 -(3-chlorophenyl)-2-[4-(4-phenoxvbenzyl]piperazin-1 -yl]ethyl)cyclohexanol dihydrochloride [0388] In an analogous manner to Example 117, 1 -0 -(3-chlorophenyl)-2-[4-(4-phenoxvbenzyl)piperazin-1-yl1ethyl)cyclohexanol dihydrochloride was prepared from 1 -[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 4-phenoxybenzaldehyde. MS (ESI) m/z 505/507 ([M+H]+); HRMS: calcd for C31CIN2O2 2.00 HCI, 576.2077; found (ESI_FT), 505.26224. Example 133: 1 -0 -(3-chlorophenyl)-2-[4-(pvridin-4-ylmethyl)piperazin-1 -yl]ethyl}cyclohexanol dihydrochloride -142- WO 2005/037279 PCT/IJS2O0-I/033732 pyridinecarboxaldehyde. MS (ESI) m/z[M+H]+ (414/416); HRMS: calcd for C24H32CIN3O 2.00 HCI, 485.1767; found (ESI), 414.2307. Example 134 : 1-0-(3-chlorophenyl)-2-[4-(pvridin-3-ylmethyl)piperazin-1-yliethyl)cyclohexanol dihydrochloride [0390] In an analogous manner to Example 117, 1-{1-(3-chlorophenyl)-2-[4-(pyridin-3-ylmethyl)piperazin-1-yl]ethyl}cyclohexanol dihydrochloride was prepared from 1-[1-(3-chioropheny!)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 3-pyridinecarboxaldehyde. MS (ESI) m/z [M+H]+ (414/416); HRMS: calcd for C24H32CIN3O • 2.00 HCI, 485.1767; found (ESI), 414.2301. Example 135: 1 -[1 -(3'.4'-dichloro-1,1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0391] Step 1: In an analogous manner to Example 1, step 1 tert-butyl 4-[(3-bromophenyl)0-hydroxycyclohexyl)acetyl1piperazine-1-carboxylate was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C23H33BrN2O4, 480.1624; found .(ESLFT), 481.16857. -143- WO 2005/037279 PCT/US20O4/O335732 [0392J Step 2: A solution of tert-butyl 4-[(3-bromophonyl)0- hydroxycyclohexyl)aceiyl]piperazine-1-carboxylate (2.12 g, 4.40 mmol) in dry tetrahydrofuran 00 mL) under nitrogen was treated dropwise with a solution of borane 0.0 M in tetrahydrofuran, 13.2 mL, 13.2 mmol). The resulting solution was heated at 70 °C for 2 h, after which time the reaction was cooled in an ice bath, treated dropwise with methanol 05 mL) and concentrated. The resulting viscous, colorless oil was re-dissolved in ethyl acetate (25 mL), washed with a saturated aqueous solution of sodium bicarbonate, water, brine, dried over sodium sulfate, filtered, and concentrated to give a white solid, which was purified via flash column chromatography (silica, gradient from 10% ethyl acetate/hexane to 20% ethyl acetate/hexane) to yleld 2.02 g (98%) tert-butyl 4-[2-(3-bromophenyl)-2-0-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate as a white powder. MS (ESI) m/z 467/469 ([M+H]+); HRMS: calcd for C23H35BrN2O3 466.1831; found (ESI), 467.1899; Anal. Calcd for C23H35BrN2O3: C, 59.10; H, 7.55; N, 5.99. Found: C, 59.14; H, 7.72; N, 5.77. [0393] Step 3: A mixture of tert-butyl 4-[2-(3-bromophenyl)-2-0- hydroxycyclohexy!)ethyl]piperazine-1-carboxylate (0.72 g, 1.55 mmol) and tetrakis(triphenylphosphine)palladium (37 mg, 0.032 mmol, 10 mol%) in 1,2- dirnethoxyethane (30 mL) was stirred for 10 min at room temperature. To this mixture was added sequentially 3,4-dichloropheny! boronic acid (0.44 g, 2.32 mmol) and a 2M aqueous solution of sodium carbonate (0.8 mL, 1.6 mmol, 5 equivalent), and the mixture was heated at reflux until all starting material was consumed and precipitation of black palladium occurred (3 h). After cooling, water was added and the reaction mixture was extracted with ethyl acetate (30 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude solid, which was purified via flash column chromatography (silica, gradient from 0% ethyl acetate/hexane to 30% ethyl acetate/hexane) to yleld 0.55 g (67%) of tert-butyl 4-[2-(3'.4'-dichloro-biphenyl-3- yl)-2-0 -hydroxycyclohexyl)ethyl1piperazine-1 -carboxylate as a foam, which was used as such in the next step. -144- W'O 2005/03727!) PCT/US2004/033732 [0394] Step 4: teri-butyl 4-[2-(3',4'-dichloro-biphenyl-3-yl)-2-0- hydroxycyclohexyl)ethyljpiperazine-1-carboxylate (0.39 g 0.73 mmol) was dissolved in diethyl ether 05 mL) then a 2N ethereal solution of hydrochloric acid 00 mL) was added. Methanol (approximately 1 mL) was then added until the resulting precipitate dissolved, and the homogeneous solution was stirred for 18 h. The precipitated product was collected by filtration, washed with diethyl ether and dried in a vacuum oven at 50 °C to yleld 0.28 g (81%) o[1 -[1 -(3'.4'-dichloro-1.1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride as a white solid. MS (ESI) m/z 433/435/437 ([M+H]+); HRMS: calcd for C24H30N2OCI2 2.00 HCI, 433.1813; found (ESI), 433.1813 Example 136: 1 -[1 -0.1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0395] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-0,1 '-biphenyl-3- yl)-2-0 -hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexy))ethyl]piperazine-1-carboxylate (see Example 135, step 2) and phenyl boronic acid. [0396] In an analogous manner to Example 135, step 4 1-[1-0.1'-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-0,1'-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z [M+H]+ (365); HRMS: calcd for C24H32N2O • 2.00 HCI, 436.2048; found (ESI), 365.2575 Example 137: 1 -[1 -(4'-chloro-1.1 '-biphenyl-3-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride -145- WO 2005/037279 PCT/US2004/033732 [0397] In an analogous manner to Example 135, step 3 tort-butyl 4-[2-(4'-chloro-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]Piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 135, step 2) and 4-chlorophenyl boronic acid. [0398] In an analogous manner to Example 135, step 4 1-[1-(4'-chloro-1,1'-biphenyl-3-yl)-2-piperazin-1 -ylethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(4'-chloro-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 399/401 ([M+H]+); HRMS: calcd for C24H31CIN2O 2.00 HCI, 470.1658; found (ESI), 399.2203. Example 138: 1-[1-(3'-methoxy-1,1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0399] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'-methoxy-biphenyl-3-yl)-2-(1-hydroxycyclohexyl]ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (see Example 135, step 2) and 3-methoxyphenyl boronic acid. [0400] In an analogous manner to Example 135, step 4 1-[1-(3'-methoxy-1.1'-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3'-methoxy-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS -146- \YL) 2OO5/037279 PCT/US2OO4/033732 (ESI) m/z395 (fM+H]+); HRMS: calcd for C25H34N2O2 2.00 HCI, 466.2154; found (ESI), 395-269. Example 139: 1 -[ 1 -(3'-chloro-1,1 '-bipheny[-3-yl)-P-Diperazin-1 -ylethylicyclohexanol dihydrochloride [0401] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'-chloro-biphenyl-3-yl)-2-(1-hydroxycyclohexyl]ethyl)piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (see Example 135, step 2) and 3-chlorophenyl boronic acid. [0402] In an analogous manner to Example 135, step 4 1-[1-(3'-chloro-1.1'-biohenyl-3- yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2- (3'-chloro-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (FS!) m/z399/401 ([M+H]+); HRMS: calcd for C24H31C!N2O 2.00 HCI, 470.1653; found (ESI), 399.2183. Example 140: 1 -[1 -(2'-fluoro-1,1 '-biphcnyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol [0403] In an analogous manner to Example 135, step 3 tort-butyl 4-[2-(2'-fluoro-biphenyl-3-yl)-2-0-hydroxycyclohexyl)ethyl1piperazine-1-carboxylate was prepared from maleate -147- WO 2005/037279 PCT/US2004/033732 tert-butyl 4-[2-(3-bromopheny!)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see-Example 135, step 2) and 2-florophenyl boronic acid. [0404] In an analogous manner to Example 135, step 4 1-[1-(2'-fluoro-1.1'-biphenyl-3- yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2- (2'-fluoro-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. The compound was neutralized with 10% aqueous potassium carbonate, and the residue dissolved in methanol. One equivalent of maleic acid was then added and the solution was concentrated. The product was triturated with diethyl ether to yleld 1-[1-(2'-fluoro-1.1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol maleate as a colorless solid. MS (ESI) m/z 383 ([M+H]+); Anal. Calcd for C24H31FN2O . C4H4O4 . 0.50 H2O: C, 66.25; H, 7.15; N, 5.52. Found: C, 66.03; H, 7.38; N, 5.31. Example 141: 1-[1-(2,5-dichlorothien-3-yl)-2-piperazine-1-ylethyl]cyclohexanol dihydrochloride [0405] Step 1: A solution of 3-thiophene acetic acid 0.42 g, 10.0 mmol) in acetic acid 00 mL) was treated with N-ch!orcsuccinimide (3.1g , 23 mmol, 2.3 equivalents), and the solution was stirred for 12 h at room temperature then concentrated in vacuo. The residue was diluted with water and stirred for 1 h whereupon the resulting solid was collected by filtration. The solid was dried in a vacuum oven at room temperature for 10 hours providing 1.51 g (72%) of (2.5-dichlorothien-3-yl)acetic acid as a brown solid, which was used as such in the next step. MS (ESI) m/z 209/211/213 ([M-H]-). -148- WO 2005/037279 PCT/US2004/OJ3732 [0406] Step 2: In an analogous manner to Example 1, step 1 tert-butyl 4-f(2.5-dichlorothienhien-3-yl)acetyl]piperazine-1 -carboxylate was prepared from 2,5-dichlorothiophene-3-acetic acid and tert-butyl 1-piperazinecarboxylate. The product was crystallized from ethyl acetate: hexane to yleld a colorless solid. [0407] Step 3: A solution of diisopropyl amine (0.80 mL, 5.6 mmol) in dry tetrahydrofuran 00mL) under nitrogen was cooled to -78 °C and treated dropwise with a solution of n-butyl]ithium 0.6 M in hexanes, 3.5 mL, 5.6 mmol). To this reaction was added dropwise a solution of tert-butyl 4-[(2,5-dichlorothien-3-yl)acetyl]piperazine-1-carboxylate 0.7 g, 4.5 mmol) in tetrahydrofuran 00 mL). After the addition was complete, the solution was stirred for 0.5 hr at -78 °C whereupon cyclohexanone (0.57 rnL, 5.6 rr.mc!) was added via syringe. The solution was stirred for an additional 0.5 h. The reaction was quenched with a saturated aqueous solution of ammonium chloride and then warmed to room temperature. The solution was diluted with ethyl acetate; the organic phase was separated, and was washed with a 2N aqueous solution of hydrochloric acid 0x10 mL). The organic extract was dried over magnesium sulfate and concentrated. Chromatography of the residue via Biotage (FLASH 40 M, silica, 30% ethyl acetate/hexane) provided 1.2 g (58%) of 4-[ (2.5-dichlorothien-3-yl)( 1 -hydroxycyclohexyl)acetyl]pioerazine-1-carboxylate as a white foam. MS (ES!) m/z 477/479/481 ([M+H]), HRMS: calcd for C21H3oCl2N2O4S, 476.1303; found (ESI), 477.1362. [0408] Step 4: In an analogous manner to Example 135, Step 2 tert-butyl 4-[2-(2,5-dichlorothien-3-yl)-2-0-hydroxvcyclohexyl)ethyl)piperazine-1 -carboxylate was prepared from tert-butyl 4-[(2,5-dichlorothien-3-yl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 463/465/467 ([M+H]+), HRMS: calcd for C21H32CI2N2O3S, 462.1511; found (ESI), 463.1594. -149- \YL) 2O05/037279 PCT/US2OO4/O33732 [2-(2,5-dichlorothien-3-y|)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate and isolated as a colorless powder. MS (ESI) m/z [M+H]+ (363/365/367); HRMS: calcd for C16H24CI2N2OS • 2.00 HCI, 434.0520; found (ESI), 363.1035. Example 142: 1-[1-(5-chlorothien-2-yl)-2-piperazin-1-ylethyl1cyclohexanol dihydrochloride [0410] In an analogous manner to Example 141, step 1 (5-chlorothien-3-yl)acetic acid vvasprepared from 2-thiopnene acetic acid and N-chiorosuccinimide. (This acid was used in Reference Example 1-rr) MS (ES) m/z 175.0 ([M-H]-) [0411] In an analogous manner to Example 1, step 1 tert-butyl 4-f(5-chlorothien-2-Yl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate was prepared from (5-ch!croth!en-2-y!)(1-hydroxycyclohexy!)acetic acid (Reference example 1-rr) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 443/445 ([M+H]+) [0412] In an analoguous manner to Example 1, step 2 1 -[ 1 -(5-chlorothien-2-yl)-2-piperazin-1-ylethy!]cyclohexanol dihydrochloride product was prepared from tert-butyl 4-[(5-chlorothien-2-yl)(1-hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z 329/331 ([M+H]+); Anal. Calcd for C16H25CIN2OS • 2.00 HCI: C, 47.83; H, 6.77; N, 6.97. Found: C, 48.31; H, 7.40; N, 6.21 Example 143: 1-[1-(5-bromothien-2-yl)-2-piperazin-1-ylethyncyclohexanol dihydrochloride -150- \YO 2OO5/O37279 PCT/US2004/033732 [0413] In an analogous manner to Example 141, step 1 (5-bromothien-3-yl)acetic acid was prepared from 2-thiophene acetic acid and N-bromosuccinimide. (This product was used in Reference Example 1-ss) [0414] In an analogous manner to Example 1, step 1, tert-butyl 4-f(5-bromothien-2-yl)(1-hydroxycyclohexyl)acetyl)pipera2ine-1-carboxylate was prepared from (5-bromothien-2-yl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-ss) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 487/489 ([M+H]+ [0415] In an analogous manner to Example 1, step 2, 1 -[ 1 -(5-bromothien-2-yl)-2-piperazin-1-ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[(5-bromothien-2-yl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 373/375 ([M+H]+). Anal. Calcd for C16H25BrN2OS 2.00 HCI: C, 43.06; H, 6.10; N, 6.28. Found: C, 43.76; H, 6.12; N, 5.50. Example 144: 1-[1-(5-chlorothien-3-yl)-2-piperazin-1-ylethyllcyclohexanol dihydrochloride -151- WO 2005/0J7279 PCT/US2OO4/O33732 [0416] In an analogous manner to Example 1, step 1 tert-butyl 4-[(5-chlorothien-3-yl)aceiyl1piperazine-1-carboxylate was prepared from 5-chlorothiophene-3-acetic acid2 and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 289.0 ([M+H-C4H8]+); HRMS: calcd for C15H21CIN2O3S, 344.0961; found (ESI), 345.1018 [0417] In an analogous manner to Example 141, step 3, tert-butyl 4-[2-(5-chlorothien-3-yl)-2-0 -hydroxycyclohexyl)ethyl]piperazine-i -carboxylate was prepared from tert-butyl 4-[(5-chlorothien-3-yl)acetyl]piperazine-1-carboxylate and cyclohexanone. MS (ESI) m/z 429 ([M+H]+); HRMS: calcd for C21H33CIN2O3S, 428.1900; found (ESI), 429.1973. [0418] In an analogous manner to Example 135, step 2, tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piprazine-1-carboxy!ate was prepared from tert butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. [0419] In an analogous manner to Example 135, step 4 1 -[1 -(5-chlorothien-3-ylV-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 329/331 ([M+H]+); HRMS: calcd for C16H25CIN2OS • 2.00 HCI, 400.0910; found (ESI), 329.1444 : Konguzzi, R.; libassi, G.; Pinra, H.; Pifferi, G. Synthesis of new a-hydrazinoarylacetic acids and derivatives. Farmaco, Ediz:one ScicntWca 0976), 31(8), 519-60 Example 145: 1 -[2-(4-aminopiperidin-1 -yl)-1 -(5-chlorothien-3-yl)ethyl]cyclohexanol dihydrochloride -152- WO 2005/037279 PCT/US2004/033732 [0420] In an analogous manner to Example 1, step 1 tert-butyl0-[2-(5-chloro-thioDhen-3-yl)-acetyl]-piperidin-4-yl}-carbamate was prepared from 5-chlorothiophene-3-acetic acid and 4-N-boc-aminopiperidine. [0421] In an analogous manner to Example 141, step 3, tert-butyl0 -[2-(5-chloro- thiophen-3-yl)(1-hydroxycyclohexyl)acetyl]-piperidin-4-yl)-carbamate was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)-acetyl]-piperidin-4-yl}-carbamate and cyclohexanone. [0422] In an analogous manner to Example 135, step 2, tert-butyl0-[2-(5-chloro-thiophen-3-yl)(1-hydroxycyclohexyl)ethyl]-piperidin-4-yl)-carbamate was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)(1-hydroxycyclohexyl)acetyl]-piperidin-4-yl}-carbamate.) [0423] In an analogous manner to Example 135, step 4 1 -[2-(4-aminopiperidin-1 -yl)-1 -(5-chlorothien-3-yl)ethyl]cyclohexanol dihydrochloride was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)(1-hydroxycyclohexyl)ethyl]-piperidin-4-yl}-carbamate. MS (ESI) m/z 343/345 ([M+H]+); HRMS: calcd for C17H27CIN2OS • 2.00 HCI, 414.1066; found (ESI), 343.1594. [0424] In an analogous manner to Example 1, step 1 t-butyl 4-[1-[1-0-benzothien-3-yl)( 1 -hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate was prepared from 1- Example 146: 1-[1-0-benzothien-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride -153- \YL) 2005/037279 PCT/UUS2004/033732 benzo{hien-3-yl(1-hydroxycyclohexyl)acetic acid (Reference Example 1-tt) and tert-butyl 1-piperaziinecarboxylate. MS (ESI) nn/z 487/489 ([M+H]+ [0425] In an analoguous manner to Example 1, step 2 1 -[1 -0 -benzothien-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from t-butyl 4-[1-[1-0-benzothien-3-yl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z [M+H]+ (345); HRMS: calcd for C2oH28N2OS 2.00 HCI, 416.1456; found (ESI), 345.2024 Example 147: 1-[1-(3'.4'-difluoro-1,1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0426] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'.4'-difluoro-biphenyl-3-yl)-2-0-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyc!ohexyl)ethyl]piperazine-1 -carboxylate (see Example 135, step 2) and 3,4-difluorophenyl boronic acid. [0427] In an analogous manner to Example 135, step 4 1-[1-(3'.4'-difluoro-1, V-biphenyl-3-yl)-2-piperazin-1-ylethyncyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3',4'-difluoro-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z [M+H]+ (401); HRMS: calcd for C24H30F2N2O • 2.00 HCI, 472.1860; found (ESI), 401.2378 Example 148: 1-[1-(3'.4'-dichloro-1.1'-biphenyl-2-yl)-2-piperazin-1-ylethyncyclohexanol dihydrochloride -154- WO 2005/037279 PCT/US2001/033732 [0428] In an analogous manner to Example 1, step 1 tert-butyl 4-[(2-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate was prepared from (2-bromophenyl)(1-hydroxycyclohGxyl)acetic acid (Reference Example 1-uu) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 481/483 ([M+H]+); HRMS: calcd for C23H33BrN2O4, 480.1624; found (ESI), 481.1689 [0429] In an analoguous manner to Example 135, step 2, tert-butyl 4-[2-(2-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl1piperazine-1-carboxylate was prepared from tert-butyl 4-[(2-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z 467/469 ([M+HJ+); HRMS: calcd for C23H35BrN2O3l 466.1831; found (ESI), 467.1895; [0430] in an analogous manner to Example 135, step 3 tert-buty! 4-['3'4 dichioro-1.1'-biphenyl-2-yl)-2-0-hydroxvcyclohexyl]ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(2-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate and 3,4-dichloro phenyl boronic acid. [0431] In an analogous manner to Example 135, step 4 1-[1-(3',4'-dichloro-1.1'-biphenyl-2-yl)-2-piperazin-1-ylethyncyclohexanol dihydrochloride was prepared from tert-butyl 4-[3'4'dichloro-1,1'-biphenyl-2-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 433.3 ([M+H]+); HRMS: calcd for C24H3oCl2N20 2.00 HCI, 504.1269; found (ESI), 433.1797 Example 149: 1 -[1 -0.1 '-biphenyl-2-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride -155- WO 2005/037279 PCT/US2004/033732 [0432] In an analogous manner to Example 135, step 3 tert-butyl 4-[11'-biphenyl-2-yl)-2-(1-hydroxvcyclohexyl)ethyl]piperazine-1 -carboxylate was prepared from tert-butyl 4-[2-(2-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 148, step 2) and phenyl boronic acid. [0433] In an analogous manner to Example 135, step 4 1 -[ 1 -0.1 '-biphenyl-2-yl)-2-piperazin-1-ylethylicyciohexanoi dihydrochloride was prepared from tert-butyl 4-[1,1'-biphenyl-2-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 365.4 ([M+H]+); HRMS: calcd for C24H32N2O 2.00 HCI, 436.2048; found (ESI), 365.2601 Example 150: 1 -[1 -(3'-chloro-1,1 '-biphenyl-2-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0434] In an analogous manner to Example 135, step 3 tert-butyl 4-[3'-chloro-1.1'-biphenyl-2-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(2-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 148, step 2) and 3-chloro phenyl boronic acid. -156- WO 2005/037279 PCT/US2004/033732 [0435] In an analogous manner to Example 135, step 4 1-[1-(3'-chloro-1,1'-biphcnyl-2-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[3'-chloro-1,1'-biphenyl-2-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 561/563/565 ([M+H]*); HRMS: calcd for C24H31CIN2O 2.00 HCI, 470.1658; found (ESI), 399.2211 Example 151:1 -{1 -[2-0,3-benzodioxol-5-yl)phenyl]-2-piperazin-1 -ylethyl}cyclohexanol dihydrochloride [0436] In an analogous manner to Example 135, step 3 tert-butyl 4-[1 -0,3-benzodioxol-5-ylphenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(2-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 148, step 2) and 3,4-(methylenedioxy) phenyl boronic acid. [0437] In an analogous manner to Example 135, step 4 1-0-[2-0,3-bcnzodioxol-5- yl)phenyl]-2-piperazin-1-ylethyl|cyclohexanol dihydrochloride was prepared from tert- butyl 4-[1 -0,3-benzodioxol-5-ylphenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 - carboxylate. MS (ES) m/z 409.3 ([M+H]*): HRMS: calcd for C25H32N2O3 2.00 HCI, 480.1946; found (ESI), 409.2483. Example 152: 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3'.4'-dichloro-1.1 '-biphenyl-3-yl)ethyncyclohexanol dihydrochloride -157- WO 2005/037270 PCT/US2004/033732 [0438] In an analogous manner to Example 135, step 3 tert-butyl 0-[(3'.4'-dichloro-1.1'-biphenyl-3-yl)0-hydroxycyclohexyl)acGtyl]piperidin-4-yl)carbamate was prepared from tert-butyl {1-[(3-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate (see Example 18, step 1) and 3,4-dichloro phenyl boronic acid. MS (ESI) m/z 561/563/565 ([M+H]+); HRMS: calcd for C3OH33CI2N204, 560.2209; found (ESI), 561.2263 [0439] In an analogous manner to Example 135, step 2 tert-butyl {1-[2-(3',4'-dichloro-1.1'-biphenyl-3-yl)-2-0-hydroxycyclohexyl)ethyllpiperidin-4-yl)carbamate was prepared from tert-butyl {1-[(3,4'-dichloro-1,1'-biphenyl-3-yl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS (ES) m/z 547.3 ([M+H]+); HRMS: calcd for C3oH40Cl2N2O3-,, 546.2416; found (ESI), 547.2473. [0440] !n an analogous manner to Example 135. step 3 1 -[2-(4-aminpiperidin-1 -yl)-1- -(3'.4'-dichloro-1.1 '-biphenyl-3-yl)Gthyl1cyclohexanol dihydrochloride was prepared from tert-butyl {1-[2-(3',4'-dichloro-1,1'-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate. MS (ES) m/z 447.2 ([M+H]+); HRMS: calcd for C25H32CI2N2O 2.00 HCI, 518.1425; found (ESI). 447.1962. Example 153: 1 -[1 -(3',4'-dichloro-1,1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclobutanol dihydrochloride -158- WO 2005/037279 PCT/US2004/033732 [0441] In an analogous manner to Example 1, step 1 tert-butyl 4-[(3-bromoDhenyl1(1-hydroxycyclobutyl)acetyl]piperazine-i-carboxylate was prepared (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C21H29BrN2O4, 452.1311; found (ESI_FT), 453.13746. [0442] In an analogous manner to Example 135, step 2 tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclobutyl)ethyl1piperazine-1-carboxylate was prepared from /erf-butyl 4-[(3-bromophenyl)(1-hydroxycyclobutyl)acetyl]piperazine-1 -carboxylate and 3,4-dichloro phenyl boronic acid. [0443] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'.4:-dichioro-biphenyl-3-yl)-2-(1-hydroxycyclobutyl)ethyl)piperazine--1-carboxy!ate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1-carboxylate and 3,4-dichloro phenyl boronic acid.. [0444] In an analogous manner to Example 135, step 4 1-[1-(3'.4'-dichloro-1.V-biphenyl-3-yl)-2-piperazin-1-ylethyl1cyclobutanol dihydrochloride was prepared from tert-butyl 4-[2-(3',4'-dichloro-biphenyl-3-yl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 405.1499 ([M+H]+); HRMS: calcd for C22H26CI2N2O 2.00 HCI, 476.0956; found (ESI), 405.1499. Example 154: 1 -[1 -0 -methyl-1 H-indol-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride -159- \YL) 2OO5/0J7279 PCT/DS2OO4/033732 [0445J In an analogous manner to Example 1, step 1 tort-butyl 4-[0- hydroxycyclohexyl)(1-methyl-1H-indol-3-yl)acetyl]piperazine-1-carboxylate was prepared from (1-methyl-1H-indol-3-yl) (1-hydroxycylclohexyl) acetic acid (Reference Example 1-xx) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 456 ([M+H]+); HRMS: calcd for C26H37N3O4, 455.2784; found (ESI_FT). 456.28501. [0446] In an analogous manner to Example 1, step 2 1 -[ 1 -0 -methyl-1 H-indol-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[(1-hydroxycyclohexyl)0 -methyl-1 H-indol-3-yl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z 342 ([M+H]+); HRMS: calcd for C21H31N3O • 2.00 HCI, 413.2001; found (ESI_FT), 342.25347 Example 155: 1-[1-0H-indol-3-yl)-2-piperazin-1-ylethyllcyclohexanol dihydrochloride [0447] In an analogous manner ti Example 1, step 1 tert-butyl 4-[0- hydroxycyclohexyl) 1 -(tert-butyl-dimethyl-silanyl)-1 H-indol-3-yl)acetyl]piperazine-1 - carboxylate was prepared from 0 -{tert-Butyl-dimethyl-silanyl)-1 H-indol-3-yl) (1-hydroxycylclohexyl) acetic acid (Reference Example 1-yy) and tert-butyl 1-piperazinecarboxylate. [0448] In an analogous manner to Example 1, step 2 1 -[1 -0 H-indol-3-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[(1-hydroxycyclohexyl)0-(tert-butyl-dimethyl-silanyl)-1H-indol-3-yl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 328 ([M+H]+); HRMS: calcd for C20H29N3O 2.00 HCI, 399.1844; found (ESI_FT), 328.23696 -160- WO 201)5/037279 PCT/l.:S2004/0337J2 Example 156: 1-[1-(2-chlorothien-3-yl)-2 -piperazin-i-ylethylicyclohexanol dihydrochloride [0449] In an analogous manner to Example 141, step 1 (2-chlorothien-3-yl)acetic acid was prepared from 2-thiophene acetic acid and 1 equivalent of N-chlorosuccinimide. MS (ESI) m/z 175/177 ([M+H]+); In an analogous manner to Example 1, step 1 tert-butyl 4-[(2-chlorothien-3-yl)acetyl]piperazine-1-carboxylate was prepared from (2-chlorothien-3-yl)acetic acid_and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 289.0 ([M+H-C4H8]+); HRMS: calcd for C15H21CIN2O3S, 344.0961; found (ESI), 345.1057. [0450] In an analogous manner to Example 141, step 3 tert-butyl 4-[(2-chlorothien-3-yl)0-hydroxycyclohexyl)acetyllpiperazine-1-carboxylate was prepared from tert-butyl 4-[(2-chlorothien-3-yl)acetyl]piperazine-1 -carboxylate and cyclohexanone. [0451] In an anlogous manner to Example 135, step 2 tert-butyl 4-[2-(2-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[(2-chlorothien-3-yl)(1-hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z 429/431 ([M+H]+); HRMS: calcd for C21H33CIN2O3S, 428.1900; found (ESI), 429.1967 [0452] In an analogous manner to Example 135, step 4 1 -[1 -(2-chlorothien-3-yl)-2-piperazine-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(2- -161- WO 2005/037279 PCT/US200-I/033732 chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 329,531 ([M+H]+); HRMS: calcd for C16H25CIN2OS 2.00 HCI, 400.0910; found (ESI), 329.1442. Example 157: 1-[1-0.1-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0453] In an analogous manner to Example 1, step 1 tert-butyl 4-[1.1'-biphenyl-4-yl(1-hydroxycyclohexyl)acetyl)piperazine-i-carboxylate was prepared from (1-hydroxycyclohexyl)0,1'-biphenyl-4-yl)acetic acid (Reference Example 1-zz) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 479 ([M+H]+); Anal. Calcd for C29H38N2O.s: C, 72.77; H, 8.00; N, 5.85. Found: C, 72.69; H, 8.39; N, 5.80. [0454] in an an2!onous manner to Example 13, step 2 1 -[1- -0 1 -biphonyl-4-y!)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[1,V-biphenyl-4-yl(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 365 ([M+H]+) HRMS: calcd for C24H32N2O . HCI, 400.2281; found (ESI_FT), 365.25908. Example 158: 1-[1-0,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1-ylethyl]cyclohexanol dihydrochloride -162- WO 2005/037279 PCT/US2004/O33732 [0455] In an analogous manner to Example 24, 1-[1-(I,i'-biphenyl-4-yl)-2-(4- methylpiperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from 1-[1-0,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 157). MS (ESI) m/z 379 ([M+H]+); HRMS: calcd for C25H34N2O HCI, 414.2438; found (ESI._FT), 379.27468. Example 159: 1-[1-(5-chlorothicn-3-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride [0456] In an analogous manner to Example 24, 1-[1-(5-chlorothien-3-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(5-chlorothien-3-yl)-2-piperazin-1-ylethyl]cyc!ohexanol (see Example 144). MS (ES) m/z 343.2 ([M+H]+); HRMS: calcd for C17H27CIN2OS. 2.00 HCI, 414.1066; found (ESI), 343.1596. Example 160: 1-[1-(3-cyanophenyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0457] Step 1: A mixture of tert-butyl 4-[2-(3-bromophenyl)-2-0- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 135, step 2) (467 mg, 1.00 mmol), zinc cyanide 041 mg, 1.20 mmol), tris(dibenzylideneacetone)dipalladium (46 mg, 0.0500 mmol), 1,1'-bis(diphenylphosphino)ferrocene (55 mg, 0.100 mmol), and zinc dust 06 mg, 0.25 mmol) in anhydrous /V,/V-dimethylformamide (5 mL) was heated at 125 °C under nitrogen until all starting material was consumed (5 h). After cooling to -163- W'O 2005/037279 PCT/US2004/033732 room temperature, water 00 mL) and a 2 N aqueous solution of ammonium hydroxide (5 ml) were added and the mixture was extracted with ethyl acetate 0 x 20 mL). The combined organic extracts were washed with brine 05 mL), dried over sodium sulfate, filtered, and concentrated to give a brown solid, which was purified via flash column chromatography (silica, gradient from 5% ethyl acetate/hexane to 30% ethyl acetate/hexane) to yleld 345 mg (84%) tert-butyl 4-[2-(3-cvanophenyl)-2-0 -hydroxycyclohexyl)ethyl]piperazine-1-carboxylate as a yellow solid. MS (ESI) m/z 414 ([M+H]+); HRMS: calcd for C24H35N3O3, 413.2678; found (ESI), 414.2745. [0458] Step 2: In an analogous manner to Example 135, step 4, 1-[1-(3-cvanophenyl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3-cyanoph9ny!)-2-0-hydrcxycyc!chsxy!)sthy!]pipsraziri£-1-carboxylate. MS (ESI) m/z 314 ([M+H]+); HRMS: calcd for C19H27N3O 2.00 HCI, 385.1688; found (ESI), 314.2225. Example 161: 1-[1-(3-cyanophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride [0459] In an analogous manner to Example 24, 1-[1-(3-cvanoohenyl)-2-(4- methylpiperazin-1-yl)ethyllcyclohexanol dihydrochloride was prepared from 1-[1-(3-cyanophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 160). MS (ES) m/z 328.2 ([M+H]+); HRMS: calcd for C20H29N3O 2.00 HCI, 399.1844; found (ESI), 328.2383. Example 162: 1-[2-piperazin-1-yl-1-(3-vinylphenyl)ethyl]cyclohexanol dihydrochloride -164- WO 2005/037279 PCT/uS2OO4/033732 [0460] Step 1: A mixture of tert-butyl 4-[2-(3-bromophenyl)-2-0- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 135, step 2) 041 mg, 0.300 mmol), tributyl(vinyl)tin 014 mg, 0.360 mmol, 1.2 equivalent), and tetrakis(triphenylphosphine)palladium 07 mg, 0.015 mmol, 5 mol%) in toluene (3 mL) was heated at reflux under nitrogen until all starting material was consumed and precipitation of black palladium occurred 0-2 h). Filtration through Celite® and purification via flash column chromatography (silica, gradient from 0% ethyl acetate/hexane to 10% ethyl acetate/hexane) ylelded 111 mg (90%) tert-butyl 4-[2-(1-hydroxycyclohexyl)-2-(3-vinylphenyl)ethyl]piperazine-1-carboxylate as a viscous colorless oil. MS (ES) m/z 415.4 ([M+H]+); HRMS: calcd for C25H38N2O3, 414.2882; found (ESI), 415.2966. [0461] Step 2: In an analogous manner to Example 135, step 4, 1-[2-piperazin-1-yl-1-(3-v'inylphenv))ethyl),cyc!ohexanol dihydrochloride was prepared from 'off-butyl 4-[2-(1-hydroxycyc!ohexyl)-2-(3-vinylphenyl)ethyl]piperazine-1-carboxylatc. MS (ESI) m/z 315 ([M+H]+); HRMS: calcd forC2oH3oN20 • 2.00 HCI, 386.1892; found (ESI), 315.242. Example 163: 1-[2-piperazin-1-yl-1-(4-vinylphenyl)ethyl]cyclohexanol dihydrochloride -165- WO 2O05/037279 PCT/U.S200-l/0J3732 [0462] In an analogous manner to Example 1, step 1 tort-butyl 4-[[4-bromophenyl)0- 1 -hydroxvcyclohexyl)acetyl]piperazine-1-carboxylate was prepared from (4-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-h) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 481/483 ([M+H]+); Anal. Calcd for C23H33BrN2O4: C, 57.38; H, 6.91; N, 5.82. Found: C, 57.06; H, 6.69; N, 5.73. [0463] In an analogous manner to Example 135, step 2, tert-butyl 4-[2-(4- bromophenyl)-2-0-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[(4-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 467/469 ([M+H]+). [0464] In an analogous manner to Example 162, step 1, tert-butyl 4-[2-0- hydroxycyclohexyl)-2-(4-vinylphenyl)ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 415.4 ([M+H]+); HRMS: calcd for C25H38N2O3, 414.2882; found (ESI), 415.2975. [0455] !n an analogous manner to Example 135T step 4, 1-[2-piperazin-1-yl-1-(4-vinylphenyl)ethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(1-hydroxycyclohexyl)-2-(4-vinylphenyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 315.3 ([M+H]+); HRMS: calcd for C2oH3oN20 • 2.00 HCI, 386.1892; found (ESI), 315.2424. Example 164: 1-[2-piperazin-1-yl-1-(4-prop-1-ynylpheny!)ethyl]cyclohexanol dihydrochloride -166- WO 2005/037279 PCT/US2004/033732 [0466] In an analogous manner to Example 162, step 1, tort-butyl 4-[2-0- hydroxycyclohexyl)-2-(4-prop-1-yl]ylphenyl)ethyl1piperazine-1-carboxylate was prepared from /ert-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using (i-propynyl)tributyltin. MS (ESI) m/z 427 ([M+H]+); HRMS: calcd for C26H38N2O3, 426.2882; found (ESI), 427.2945. [0467] In an analogous manner to Example 135, step 4, 1 -[2-piperazin-1 -yl-1 -(4-prop-1 -yl]ylphenyl)ethyl]cyclohexanol dihydrochloride was prepared from tort-butyl 4-[2-(1-hydroxycyclohexyl)-2-(4-prop-1 -ynylphenyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 327 ([M+H]+); HRMS: calcd for C21H3oN20 2.00 HCI, 398.1892; found (ESI), 327.2425. Example 165: 1 -[1 -(2'-chloro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0468] Step 1: In an analogous manner to Example 135, step 3, tort-butyl 4-[2-(2'-ch!oro-1,1'-bipheny!-4-y!)-2-(1-hydroxycyc!ohexyl)ethyl]pipernzine-1-carboxylate was prepared from tort-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using 2-chlorophenylboronic acid. MS (ESI) m/z 499 ([M+H]+); HRMS: calcd for C29H39CIN2O3, 498.2649; found (ESI), 499.2745. [0469] Step 2: In an analogous manner to Example 135, step 4, 1-[1-(2'-chloro-1.V-biphenyl-4-yl)-2-piperzin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from tort-butyl 4-[2-(2'-chloro-1,1-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1- -167- WO 2005/037279 PCT/US2004/033732 carboxylate. MS (ESI) m/z 399 ([M+H]+); HRMS: calcd for C24H31C\N2O 2.00 HCI, 470.1658; found (ESI), 399.2200. Example 166: 1 -[1 -(3'-fluoro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0470] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(3'-fluoro-1.1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl1piperazine-1-carboxylate was prepared from /e/t-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using 3-fluorophenylboronic acid. MS (ESI) m/z 483 ([M+H]+); [0471] In an analogous manner to Example 135, step 4, 1-[1-(3'-fluoro-1.1'-biphenyl-4-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3'-fluoro-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 383.3 ([M+H]+); HRMS: calcd for C24H31FN2O 2.00 HCI, 454.1954; found (ESI), 383.2494. Example 167: 1 -[1 -(3'-chloro-1.1 '-biphenyl-4-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride -168- WO 2005/037279 PCT/US2O04/033732 [0472] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(3'-chloro-1.1'-biphenyl-4-yl)-2-0-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from fert-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (see Example 163, step 2) using 3-chlorophenylboronic acid. MS (ES) m/z 499.3 ([M+H]+); HRMS: calcd for C29H39CIN2C3, 498.2649; found (ESI), 499.2738. [0473] In an analogous manner to Example 135, step 4, 1 -[1 -(3'-chloro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3'-chloro-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 399/401 ([M+Hf); HRMS: calcd for C24H31CIN2O • 2.00 HCI, 470.1658; found (ESI), 399.2211. Example 168: 1-|1-(3'-cvano-1,1:-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0474] In an analogous manner to Example 135, step 3, /erf-butyl 4-[2-(3'-cyano-1.1'-biphenyl-4-yl)-2-0-hydroxycyclohexyl)ethyl1piperazine-1-carboxylate was prepared from /erf-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate -169- WO 2005/037279 PCT/US20O4/033732 (see Example 163, step 2) using 3-cyanophenylboronic acid. MS (ESI) m/z 490 ([M+H]+); [0475] In an analogous manner to Example 135, step 4, 1-[1-(3'-cvano-1.1'-biphenyl-4-yl)-2-piperazin-1 -ylethyl)cyclohexanol dihydrochloride was prepared from /erfbutyl 4-[2-(3'-cyano-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyljpiperazine-1-carboxylate. MS (ES) m/z 390.3 ([M+H]+); HRMS: calcd for C25H31N3O 2.00 HCI, 461.2001; found (ESI), 390.2532. Example 169: 1-[1-(3'-nitro-1.1'-biphenyl-4-yl)-2-piperazin-1-ylethyncyclohexanol dihydrochloride [0476] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-0- hydroxycyclohexyl)-2-(3'-nitro-1.1 '-biphenyl-4-yl)ethylipiperazine-1 -carboxylate was prepared from /er/-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using 3-nitrophenylboronic acid. MS (ES) m/z 510.3 ([M+H]+); [0477] In an analogous manner to Example 135, step 4, 1 -[ 1 -(3'-nitro-1.1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from /erf-butyl 4-[2-(1-hydroxycyclohexyl)-2-(3'-nitro-1,1'-biphenyl-4-yl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 410.3 ([M+H]+); HRMS: calcd for C24H31N3O3 2.00 HCI, 481.1899; found (ESI), 410.2452. -170- wO 2005/037279 PCT/US20O4/033732 E_xample 170: 1-[1-(3'-methoxy-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyllcyclohexanol dihydrochloride [0478] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-0- hydroxycyclohexyl)-2-(3'-methoxy-1.1'-biphenyl-4-ynethynpiperazine-1-carboxylate was prepared from /erf-butyl 4-[2-(4-bromophenyl)-2-(i-hydroxycyciohexyl)et'nyljpiperazine-1-carboxylate (see Example 153, step 2) using 3-methcxypneny!boron:c acid. MS (ES) m/z495.4 ([M+H]+); [0479] In an analogous manner to Example 135, step 4, 1-[1-(3'-methoxy-1.1'-biphenyl-4-yl)-2-piperazin-1-ylethyl1cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(1-hydroxycyclohexyl)-2-(3'-methoxy-1,1'-biphenyl-4-yl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 395.4 ([M+H]+); HRMS: calcd for C25H34N2O2 2.00 HCI, 466.2154; found (ESI), 395.2697. Example 171: 1-{2-piperazin-1-yl-1-[3'-(trif!uoromethoxy)-1,1'-bipheny!-4-. yl]ethyl)cyclohexanol dihydrochloride -171- WO 2005/037279 PCT/11S2004/033732 [0480] In an analogous manner to Example 135, step 3, tert-butyl 4-(2-0- hyd'roxvcyclohexyl)-2-[3'-(trifluoromethoxy)-1,1'-biphenyl-4-yl1ethyl)pipera2ine-1- carboxylate was prepared tert-butyl 4-[2-(4-bromophenyl)-2-0- hydroxycyclohexyl)ethyl]piperazine-1-carboxylato (see Example 163, step 2) using 3-trifluoromethoxy phenylboronic acid. MS (ES) m/z 549.4 ([M+H]+). [0481] In an analogous manner to Example 135, step 4, 1 -(2-piperazin-1 -yl-1 -[3'-(trifluoromethoxy)-1. 1 '-biphenyl-4-yl]ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-{2-(1-hydroxycyclohexyl)-2-[3'-(trifluoromethoxy)-1,1'-biphenyl-4-yl]ethyl}piperazine-1 -carboxylate. MS (ES) m/z 449.3 ([M+H]+); HRMS: calcd for C25H31[3N2O2 2.00 HCI, 520.1871; found (ESI), 449.2389. Example 172: 1 -[ 1 -(4'-chloro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0482] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(4'-chloro-1,1-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]pipera^ine-1-carboxylate was prepared from tert-buty! 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (see Example 163, stop 2) using 4-chlorophenylboronic acid. MS (ESI) m/z 499 ([M+HH; HRMS: calcd for C2oH39CIN2O3l 498.2649; found (ESI), 499.2718; [0483] In an analogous manner to Example 135, step 4, 1 -[1-(4'-chloro-1,1 '-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from tert-buty! 4-[2-(4-ch!oro-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. -172- WO 2005/037279 PCT/US2004/033732 MS (ESI) m/z 399 ((M+H]+); HRMS: calcd for C24H31CIN2O 2.00 HCI, 470.1658; found (ESI), 399.2209. Example 173: 1-[1-[3',4'-dichloro-1.1'-binhenyl-4-yl)-2-pipe razin-1 -ylethyl]cyclohexanol dihydrochloride [0484] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(3'.4'-dich!oro-1.1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from /erf-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using 3,4-dichlorophenylboronic acid. MS m/z 533/535/537 ([M+H]+); HRMS: calcd for C29H38CI2N2O3, 532.2259; found (ESI), 533.2329. [0485] In an analogous manner to Example 135, step 4, 1-[1-(3'.4'-dichloro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl1cyclohexanol dihydrochloride was prepared from /erf-butyl 4-[2-(3',4'-dichloro-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 433 ([M+H]+); HRMS: calcd for C24H30CI2N2O • 2.00 HCI, 504.1269; found (ESI), 433.1793. Example 174: 1-[2-piperazin-1-yl-1-(4-thicn-3-ylphenyl)ethyl]cyclohexanol dihydrochloride -173- WO 2005/037279 PCT/US2OO4/033732 [0486] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-0- hydroxycyclohexyl)-2-(4-thien-3-ylphenyl]ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using 3-thiopheneboronic acid. MS (ES) m/z 471.3 ([M+HD; HRMS: calcd for C27H38N2O3S, 470.2603; found (ESI), 471.2678. [0487] In an analogous manner to Example-135, step 4, 1 -[2-piperazin-1 -yl-1 -(4-thien-3-ylphenyl)ethyl1cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(1-hydroxycyclohexyl)-2-(4-thien-3-ylphenyl)ethyl]piperazine-1-carboxylate. MS m/z 371 ([M+H]+); HRMS: calcd for C22H3oN2OS • 2.00 HCI, 442.1612; found (ESI), 371.2144. Example 175: 1-[1-(2'-chloro-1,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride [0488] In an analogous manner to Example 24, 1 -[1 -(2'-chloro-1,1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(2'-chloro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 165). MS (ESI) m/z 413/415 ([M+H]+); HRMS: calcd for C25H33CIN2O 2.00 HCI, 484.1815; found (ESI), 413.2365. -174- WO 2005/037279 PCT/US2004/033732 Example 176: 1-[1-[3'-chloro-1.1-.biphenyl-4-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride [0489] In an analogous manner to Example 24, 1-[1-(3'-chloro-1,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(3'-chioro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 167). MS (ES!) m/z 413/415 ([M+H]+); HRMS: ca!cd for C25H33CIN2O 2.00 HCI, 484.1315; found (ESI), 413.2347. Example 177: 1-[1-(3'-cvano-1.1'-biphenyl-4-yl)-2-(4-methylpiperazin-1-ynethyl]cyclohexanol dihydrochloride [0490] In an analogous manner to Example 24, 1 -[ 1 -(3'-cyano-1,1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(3'-cyano-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 168). MS (ESI) m/z 404 ([M+H]+); HRMS: calcd for C26H33N3O 2.00 HCI, 475.2157; found (ESI), 404.2708. -175- WO 2005/037279 PCT/US2004'033732 Examplo 178: 1 -[2-(4-methv1piperazin-1 -yl)-1 -(3'-nitro-1.1 '-binhenyl-4-yl)ethyllcyclohexanol dihydrochloride [0491] In an analogous manner to Example 24, 1 -[2-(4-methylpiperazin-1 -yl)-1-(3'-nitro-1.1'-biphenv)-4-yl)ethv)lcyclohexanol dihydrochloride was prepared from 1-[1-(3'-nitro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 169). MS (ESi) m/z 424 ([M+H]+); HRMS: calcd for C25H33N3O3 2.00 HCI, 495.2055; found (ESI), 424.2603. Example 179: 1 -[1 -(3'-methoxy-1.1 '-biphenyl-4-yl)-2-(4-rnethylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride [0492] In an analogous manner to Example 24, 1 -[1 -(3'-methoxy-1.1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(3'-methoxy-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 170). MS (ESI) m/z 409 ([M+H]+); HRMS: calcd for C26H36N2O2 ' 2.00 HCI, 480.2310; found (ESI), 409.2844. -176- WO 2005/037279 PCT/US2004/033732 Example 180: 1 -[ 1 -(4'-f luoro-1.1-biphenyl-4-yl)-2-(4-mRthylniperazin-1 -yl)ethyJloyclohexanol dihydrochloride [0493] In an analogous manner to Example 1, step 2, 1 -[1 -(4-bromophenyl)-2-piperazin-i-ylethyncyclohexanol was prepared from tert-butyl 4-[(4-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate (see Example 163, step 1). MS (ESI) m/z 367/369 ([M+H]+); HRMS: calcd for C18H27BrN2O 2.00 HCI, 438.0840; found (ESI), 367.1365. [0494] In an analogous manner to Example 24, 1 -[ 1 -(4-bromophenyl)-2-(4- methylpiperazin-1-yl)ethyncyclohexanol was prepared from 1-[1-(4-bromophenyl)-2-piperazin-1-ylethyl]cyclohexanol. MS (ESI) m/z 381/383 ([M+H]+); HRMS: calcd for C40H29BrN2O, 380.1463: found (ESI). 381.1525. [0495] In an analogous manner to Example 135, step 3, 1-[1-(4'-fluoro-1.1'-biphenyl-4- yl)-2-(4-methylpiperazin-1-yl)ethyncyclohexanol dihydrochloride was prepared from 1-[1- (4-bromophenyl)-2-(4-methylpiperazin-1 -y!)ethyl]cyclohexanol using 4- fluorophenylboronic acid. Salt formation: A solution o[1-[1-(4'-f!uoro-1,1'-biphenyl-4-yl)- 2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol, in diethyl ether (2 mL) was treated with a 4 N solution of hydrogen chloride in dioxane 0 mL) and stored in the refrigerator for 16 h. The resulting crystals were collected, washed with diethyl ether, and dried in vacuo to yleld 1-[1-(4'-fluoro-1,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride. MS (ESI) m/z 397 ([M+H]+); HRMS: calcd for C25H33FN2O • 2.00 HCI, 468.2110; found (ESI), 397.2639 -177- WO 2005/037279 PCT/US2004/033732 Example 181:1 -11 -(4'-methyl-1,1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride [0496] In an analogous manner to Example 135, step 3, 1 -[1-(4'-methyl-1.1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1-yl)ethyl'lcyclohexanol dihydrochloride was prepared from 1-[1-(4-bromophenyl)-2-(4-methyloiperazin-1-yl)ethyl]cyc!ohexano! (see Example 180, step 3) using 4-tolylboronic acid. Salt formation: A solution o[1-[1-(4'-methyl-1,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol, in diethyl ether (2 ml) was treated with a 4 N solution of hydrogen chloride in dioxane 0 mL) and stored in the refrigerator for 16 h. The resulting crystals were collected, washed with diethyl ether, and dried in vacuo to yleld 1 -[1 -(4'-methyl-1,1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl]ethylicyclohexanol dihydrochloride. MS (ESI) m/z 393 ([M+H]+);; HRMS: calcd for C26H35N2O 2.00 HCI, 464.2361; found (ESI), 393.2913. Example 182: 1-[1-(3'-chloro-1.1'-biphenyl-4-yl)-2-piperazin-1-ylethyncyclobutanol dihydrochloride [0497] In an analogous manner to Example 1, step 1, tert-butyl 4-f(4-bromophenyl)(1-hydroxycyclobutyl)acetyl]piperazine-1-carboxylate was prepared from (4- -178- WO 2005/037279 PCT/US2OO4/O33732 bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-ww) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 453/455 ([M+H]+); [0498] In an analogous manner to Example 135, step 2, tert-butyl 4-[2-(4- bromophenyl)2-(1-hydroxycyclohutyl)ethyl]piperazine-1-carboxylate was prepared from te/t-butyl 4-[(4-bromophenyl)(1-hydroxycyclobutyl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z 439/441([M+H]+); [0499] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(3'-chloro-1.1 '-biphenyl-4-yl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1-carboxylate was prepared from te/t-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1 -carboxylate using 3-chlorophenylboronic acid. MS (ES) m/z 471.3 ([M+H]+); HRMS: calcd for C27H35CIN2O3, 470.2336; found (ESI), 471.2405. [0500] In an analogous manner to Example 135, step 4, 1-[1-(3'-chloro-1.1'-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyclobutanol dihydrochloride was prepared from te/t-butyl 4-[2-(3'-chloro-1,1 '-biphenyl-4-yl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1 -carboxylate. MS (ES) m/z 371.3 ([M+H]*); HRMS: calcd for C22H27CIN2O 2.00 HCI. 442.1345; found (ESI), 371.1897. Example 183: 1 -(2-piperazin-1 -yl-1 -[3'-(trifluoromethoxy)-1.1 '-biphenyl-4-yliethyl)cyclobutanoi dihydrochloride -179- WO 2005/0J7279 PCT/US2004/0.53732 [05.A1] In an analogous manner to Example 135, stop 3, tert-butyl 4-{2-0- hydroxycyclobutyl]-2-[3'-(trifluoromethoxy)-1.1 '-biphenyl-4-yl]ethyl)Dip9ra?ine-1 -carboxylate was prepared from tert-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1-carboxylate (see Example 182, step 2) using 3-trifluoromethoxyphenylboronic acid. MS (ES) m/z 521.4 ([M+HD; HRMS: calcd for C28H35[3N2O4, 520.2549; found (ESI), 521.2639. [0502] In an analogous manner to Example 135, step 4, 1-{2-piperazin-1-yl-1-[3'-(trifluoromethoxy)-i. 1 '-biphenyl-4-yl]ethyl)cyclobutanol dihydrochloridc was prepared from tert-butyl 4-{2-(1-hydroxycyclobutyl)-2-[3'-(trifluoromethoxy)-1,1'-biphenyl-4-yl]ethyl}piperazine-1-carboxylate. MS (ES) m/z 421.3 ([M+HD; HRMS: calcd for C??H27[3N2O2 ¦ 2.00 HCL 492.1558; found (ESI), 421.2097. Example 184: 1-[1-(3'.4'-dichloro-1,1'-biphenyl-4-yl]-2-piperazin-1-ylethyl1cyclobutanol dihydrochloride [0503] In an analogous manner to Example 135, step 3, /e/t-butyl 4-|2-(3',4'-dichloro-1,T-biphenyl-4-yl)-2-(1-hydroxycyclobutyl)Gthyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1 -carboxylate (see Example 182, step 2) using 3,4-dichlorophenylboronic acid. MS (ES) m/z 505.3 ([M+H]+); HRMS: calcd for C27H34CI2N2O3, 504.1946; found (ESI), 505.2036. [0504] In an analogous manner to Example 135, step 4, 1-[1-(3'.4'-dichloro-1,1'-biphenyl-4-yl]-2-piperazin-1-ylethyl1cyclobutanol dihydrochloride was prepared from tert- -180- WO 2005/037279 PCT/US20O.J/033732 butyl 4-[2-(3',4'-dichloro-1,r-biphenyl-4-yl)-2-(1-hydroxycyclobutyl)Gthyl]pipGrazine-1-carboxylate. MS (ES) m/z 405.3 ([M+H]+); HRMS: calcd for C2?H26Cl2N2O 2.00 HCI, 476.0956; found (ESI), 405.1486. Example 185: 1 -[1 -(3'.5'-dichloro-1.1 '-biphenyl-4-yl)-2-piperazin-1 -ylethylicyclobutanol dihydrochloride [0505] In an analogous manner to Example 135, step 3, y -butyl 4-[2-(3'.5'-dichloro-1.1'-biphenyl-4-yl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1-carboxylate was prepared from y -butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1 -carboxylate (see Example 182, step 2) using 3,5-dichlorophenylboronic acid. MS (ES) m/z 505.2 ([M+H]+); HRMS: calcd for Ca/H.^CI^Cb, 504.1946; found (ESI), 505.2007; [0506] In an analogous manner to Example 135, step 4, 1-[1-(3'.5'-dichloro-1,1'-biphenyl-4-yl)-2-pipera7.in-1-ylethyl1cyclobutanol dihydrochloride was prepared from tert-butyl 4-[2-(3',5'-dichloro-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 405.2 ([M+H]+); HRMS: calcd for C22H2GCI2N2O 2.00 HCI, 476.0956; found (ESI), 405.151. Example 186: 1-(2-[(3fi)-3-(methylamino)piperidin-1-yl]-1-[3-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride -181- WO 2005/037270 PCT/IJS2004/033732 [0507] In an analogous manner to Example 1, step 1 fert-butyl ((3f?)-1-((1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl)piperidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and (R)-(-f)-3-t-butoxycarbonylaminopiperidine (Moon, S.; Lee, S., Synth. Commun. 1998, 28(21), 3919-3926.) MS (ES) m/z 501.1 [0508] In an analogous manner to Example 13, step 2 1-{2-[(3R)-3-(rnethylamino)piperidin-1-yll-1-[3-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from tort-butyl ((3R)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}piperidin-3-yl)carbamate. MS m/z 401; HRMS: calcd for C2,H31[3N2O2 + H, 401.24159; found (ESI, [M+H]+), 401.2406. Example 187: 1-(2-[(3R)-3-aminopiperidin-1-yl]-1-[3-(trifluoromethoxy)phenyl1ethyl)cyclohexanol dihydrochloride [0509] In an analogous manner to Example 1, step 1 y -butyl ((3fl)-i-f(i-hydroxycyclohexyl][3-(trifluoromethoxy)phenyl]acetyl)piperidin-3-yl)carbamate was -182- WO 2005/037279 PCT/US2OOJ/033732 prepared from (i-hydroxycyclohoxyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and (R)-(*)-3-t-butoxycarbonylaminopiperidine (Moon, S.; Lee, S., Synth. Commun. 1998,28(21), 3919-3926.) MS (ES) m/z 501.1 [0510] In an analogous manner to Example 1, step 2 1-(2-[(3R)-3-aminopiperidin-1-yl]-1-[3-(trifluoromethoxy)phenvHethyl)cyclohexanol dihydrochloride was prepared from tert-butyl ((3R)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}piperidin-3-yl)carbamate. HRMS: calcd for C2oH29[3N202 + H, 387.22594; found (ESI, [M+H]+), 387.2248. Example 188: 1-(2-[(3ff)-3-(dimethylamino)piperidin-1-yl]-1-[3-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride [0511] In an analogous manner to Example 36, 1-(2-[(3f?)-3-(dimethylamino)piperidin-1 -yl]-1 -[3-(trifluororrtethoxy)phenvHethyl)cyclohexanol dihydrochloride was prepared from 1-{2-[(3/:?)-3-aminopiperidin-1-yl1-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol (See Example 187). MS (ESI) m/z 415; HRMS: calcd for C22H33[3N2O2 + H, 415.25724; found (ESI, [M+H]+), 415.2596. Example 189: 1-(2-[(3S)-3-(methylamino)piperidin-1-yl]-1-[3-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride -183- WO 2005/037279 PCT/US20fM/033732 [0512] In an analogous manner to Example 1, step 1, fort-butyl ((3S)-1-((1-hydroxycyclohexyl)[3-ftrifluoromethoxy)phenyl]acetyl)piperidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and (S)-(+)-3-t-butoxycarbonylaminopiperidine (Moon, S.; Lee, S., Synth. Commun. 1998, 28(21), 3919-3926.) MS (ES) m/z 501.1 [0513] In an analogous manner to Example 13, step 2, 1-(2-[(3S)-3-(methylamino)piperidin-1-yn-1-[3-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from fert-butyl ((3S)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]aceiyl}piperidin-3-yl)carbamate. MS m/z 401; HRMS: calcd for C21H3i[3N2O2 + H, 401.24159; found (ESI. [M+H]+), 401.2419. Example 190: 1-(2-[(3S)-3-aminopiperidin-1-yl1-1-[3-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride [0514] In an analogous manner to Example 1, step 1, fert-butyl ((3S)-1-((1-hydroxycyclohexyl)[3-(trifluoromethoxy)Dhenyl]acetv[)piperidin-3-yl)carbamate was -184- WO 2005/037279 PCT/US2O04/0.5J732 prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and (S)-(+)-3-t-butoxycarbonylaminopiperidino (Moon, S.; Lee, S., Synth. Commun. 1998, 28(21), 3919-3926.) MS (ES) m/z 501.1 [0515] In an analogous manner to Example 1, step 2, 1 -(2-[(35)-3-aminopiperidin-1 -yl]-1-[3-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl ((3F?)-1 -{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}piperidin-3-yl)carbamaie. HRMS: calcd for C20H29[3N2O2 + H, 387.22594; found (ESI, [M+H]+), 387.2248. Example 191: 1-(2-[(35)-3-(dimethylamino)piperidin-1-yl]-1-[3-(trifluoromethoxy)phenyl1ethyl)cyclohexanol dihydrochloride [0516] In an analogous manner to Example 36, 1-(2-[(35)-3-(dimethylamino)piperidin-1-yl]-1-[3-(trifluoromethoxy)phenyl1ethyl}cyclohexanol dihydrochloride was prepared from 1 -{2-[(3S)-3-aminopiperidin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl]Gthyl}cyclohexanol (See Example 190). MS (ESI) m/z 415; HRMS: calcd for C22H33[3N2O2 + H, 415.25724; found (ESI, [M+H]+), 415.2549. Example 192: 1-0-[4-(BenzyloxyV3-chlorophenyl]-2-[(3/:?)-3-(methylamino)piperidin-1- yliethyDcyclohexanol dihydrochloride -185- WO 2005/037279 PCT/US2004/033732 [0517] In an analogous manner to Example 1, step 1, te/t-butyl ((3f?)-1-f[4-(Benzyloxy)-3-chlorophenyl]f1-hydroxycyclohexyl)acetyl]piperidin-3-yl)carbamate was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetic acid (Reference Example 1-eee) and (R)-(+)-3-t-butoxycarbonylaminopiperidine (Moon, S.; Lee, S., Synth. Commun. 1998, 28(21), 3919-3926.) MS (ES) m/z 557.1 [0518] In an analogous manner to Example 13, step 2, 1-0-[4-(benzyloxy)-3-chlorophenyl)-2-[(3R)-3-(methylamino)piperidin-1-ynethyl)cyclohexanol dihydrochloride was prepared from tert-butyl {(3/:?)-1-[[4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetyl]piperidin-3-yl}carbamate. MS m/z457; HRMS: calcd for C27H37CIN2O2 + H, 457.26218; found (ESI, [M+H]+), 457.2622. Example 193: 1-(2-f[3ffl-3-aminooiperidin-1-yl1-1-[4-(benzyloxy)-3-chlorophenyl]ethyl]cyclohexanol dihydrochloride [0519] In an analogous manner to Example 1, step 1, tert-butyl ((3R)-1-[[4-(BenzyloxyV3-chlorophenyl]( 1 -hydroxycyclohexyl)acetyl]piperidin-3-yl)carbamate was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetic acid -186- WO 2005/037279 PCT/US2004/03J732 (Reference Example 1-eee) and (R)-(+)-3-t-butoxycarbonylaminopiperidine (Moon, S.; Lee, S., Synth. Commun. 1998, 28(21), 3919-3926.) MS (ES) m/z 557.1 [0520] In an analogous manner to Example 1, step 2, 1 -(2-[(3R)-3-aminopiperidin-1 -yll-1-[4-(Benzyloxy)-3-chlorophenyl]ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl {(3F?)-1-[[4-(benzyloxy)-3-chlorophenyl]0- hydroxycyclohexyl)acetyl]piporidin-3-yl}carbamate. MS m/z 443; HRMS: calcd for C26H3sCIN2O2 + H, 443.24653; found (ESI, [M+H]+), 443.2487. Example 194: 1-0-[4-(Benzyloxy)-3-chlorophenyl]-2-[(3fl)-3-(dimethylamino)Diperidin-1- yl]ethyl)cyclohexanol dihydrochloride [0521] In an analogous manner to Example 36, 1-0-[4-(benzyloxy)-3-chlorophenyn-2-[(3R)-3-(dimethylamino)piperidin-1-yl]ethyl|cyclohexanol dihydrochloride was prepared from 1-{2-[(3R)-3-aminopiperidin-1-yl]-1-[4-(bonzyloxy)-3- chlorophenyl]ethyl}cyclohexanoliSee Example 193). MS (ESI) m/z415; HRMS: calcd for C2oH39CIN202 + H, 471.27783; found (ESI, [M+H]+), 471.2767. Example 195: 1 -1 -[4-(Benzyloxy)-3-chlorophenyl]-2-[(35)-3-(methylamino)piperidin-1 - yliethyllcyclohexanol dihydrochloride -187- WO 2005/037279 PCT/US2OCI4/0J37J2 [0522] In an analogous manner to Example 1, step 1, y -butyl U3S)-H[4-(Benzyloxy)-3-chlorophcnyl](1-hydroxycyclohexyl]acetyliDiperidin-3-yl)carbamate was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetic acid (Reference Example 1-eee) and (S)-(+)-3-t-butoxycarbonylaminopiperidine (Moon, S.; Lee, S.. Synth. Commun. 1998, 28(21), 3S19-3926.) MS (ES) m/z 557.1 [0523] In an analogous manner to Example 13, step 2, 1-0-[4-(benzyloxy)-3-chlorophenyl]-2-[(3S)-3-(methylamino)Diperidin-1-yl1ethyl)cyclohexanol dihydrochloride was prepared from te/t-butyl {(3S)-1-[[4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetyl]piperidin-3-yl}carbamate MS m/z 457; HRMS: calcd for C27H37CIN2O2 + H, 457.26218; found (ESI, [M+H]+), 457.2619 Example 196: 1 -(2-[(3S)-3-aminopiperidin-1 -yl]-1 -[4-(benzyloxy)-3-chlorophenyl]ethyllcyclohexanol dihydrochloride [0524] In an analogous manner to Example 1, step 1, tert-butyl K3S)-1-[[4-(benzyloxy)-3-chlorophenvH(1-hydroxycyclohexyl]acetynpiperidin-3-yl}carbamate was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetic acid (Reference Example 1-eee) and (S)-(+)-3-t-butoxycarbonylaminopiperidine (Moon, S.; Lee, S., Synth. Commun. 1998, 28(21), 3919-3926.) MS (ES) m/z 557.1 [0525] In an analogous manner to Example 1, step 2, 1 -(2-r(35)-3-aminopiperidin-1 -yl]-1-[4-(Benzyloxy)-3-chlorophenyl]ethyl)cyclohexanol dihydrochloride was prepared -188- WO 2005/037279 PCT/US2004/033732 from .tert-butyl {(3S)-1 -[[4-(benzyloxy)-3-chlorophenyl]0 - hydroxycyclohexyl)acetyl]piperidin-3-yl}carbamate. MS m/z443; HRMS: calcd for C2GH35CIN2O2 + H, 443.24653; found (ESI, [M+H]+), 443.2482. Example 197: 1-0-[4-(Benzyloxy1-3-chlorophonyl]-2-[(3S)-3-(dimethylamino^piDeridin-1- yliethyl)cyclohexanol dihydrochloride [0526] In an analogous manner to Example 36, 1 -1 -[4-(Benzyloxy)-3-chlorophenyl]-2-[(3S)-3-(dimethylamino)piperidin-1-yl]ethyl)cyclohexanol dihydrochloride was prepared from 1-{2-[(3S)-3-aminopiperidin-1-yl]-1-[4-(bcnzyloxy)-3- chlorophenyl]ethyl}cyclohexanol_{See Example 196). HRMS: calcd for C28H29CIN2O2 + H, 471.27783; found (ESI, [M+H]4), 471.2766. Example 198: 1-1-0-(3-chlorophenyl)-2-r(3S)-3-(methylamino)pyrrolidin-1-yl]ethyl)cyclohexanol dihydrochloride -189- WO 2005/037279 PCT/US2004/033732 [0527] In an analogous manner to Example 1, step 1, tert-butyl ((3SH-K3-chlor-Qphenyl)M-hydroxycyclohexyl)acetyl]pvrrolidin-3-yl)carbamate was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1a) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 437.0 [0528] In an analogous manner to Example 13, step 2, 1 -0 -(3-chlorophenyl)-2-[(3SV 3-(methylamino)pyrrolidin-1-vHethyl)cyclohexanol dihydrochloride was prepared from y -butyl {(3S)-1-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]pyrrolidin-3-yl}carbamate MS (ES) m/z 337.2; HRMS: calcd for C19H29CIN2O + H, 337.20467; found (ESI, [M+H]+), 337.2034. Example 199: 1 -0 -[3-chlorophenyl)-2-[(3S)-3-(dimethylamino)pyrrolidin-1 -yl]ethyljcyclohexanol dihydrochloride [0529] In an analogous manner to Example 36, 1 -0 -(3-chlorophenyl)-2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]ethyl)cyclohexanol dihydrochloride was prepared from 1 -{1 -(3-chlorophenyl)-2-[(3S)-3-(methylamino)pyrrolidin-1 -yl]ethyl}cyclohexanol (See Example 198). MS (ES) m/z 351.1; HRMS: calcd for C2oH3iCIN20 + H, 351.22031; found (ESI, [M+H]+), 351.2189. Example 200: 1-0-(3-chlorophenyl)-2-[(3fl)-3-(methylamino)pvrrolidin-1-yliethyl)cyclohexanol dihydrochloride -190- WO 2005/037279 PCT/US2004/033732 [0530] In an analogous manner to Example 1, step 1, y -butyl ((3R)-1-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]pyrrolidin-3-yl)carbamate was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1a) and (3R)-(-)-3-(tert-butoxycarbonylamino)pyrrolidinG. MS m/z 437 [0531] In an analogous manner to Example 13, step 2, 1 -0 -(3-chlorophenyl)-2-[(3F?)-3-(methylarnino)pvrrolidin-1-yl]ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl {(3f?)-1-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]pyrrolidin-3-yl}carbamate MS (ES) m/z337.1; HRMS: calcd for C1SH29CIN2O + H, 337.20467; found (ESI, [M+H]*), 337.2043. Example 201: 1 -[2-[(3f?)-3-aminopyrrolidin-1 -yl]-1 -O-chlorophenyQcthylicyclohexanol dihydrochloride [0532] In an analogous manner to Example 1, step 1, fert-butyl [(3fl)-1-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl1pyrrolidin-3-yl}carbamate was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1a) and (3R)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS m/z 437 -191- W'O 2005/037279 PCT/US2OO-I/0J37J2 [0533] In an analogous manner to Example 1, step 2, 1 -^-fO^-S-aminopyrrolidin-i -yl]-U(3-chloroPhenyl)ethyl]cyclohexanol dihydrochloride was prepared from y -butyl {(3R)-1-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]pyrrolidin-3-yl}carbamate MS (ESI) m/z323; HRMS: calcd for C,SH27CIN2O + H, 323.18901; found (ESI, [M+Hf), 323.1895. Example 202: 1 -0 -(3-chlorophenyl)-2-[(3R)-3-(dimethylamino)pvrrolidin-1 -yl]ethyl)cyclohexanol dihydrochloride [0534] In an analogous manner to Example 36, 1 -[1 -(3-chlorophenyn-2-[(3f?)-3-(dimethylamino)pyrrolidin-1-yl1ethyl)cyclohexanol dihydrochloride was prepared from 1-[2-[(3/7)-3-aminopyrrolidin-1 -yl]-1 -(3-chlorophenyl)ethyl]cyclohexanol (See Example 201). MS (ESI) m/z351; HRMS: calcd for C20H3iCIN2O + H, 351.22031; found (ESI, [M+H]+), 351.2193. Example 203: 1-[2-[(3S)-3-(methylamino)pyrrolidin-1-yl]-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride -192- \YL) 20f)5/nj7279 PCT/US2O04/03J732 [0535] In an analogous manner to Example 1, step 1, tert-butyl U3SV1-f(1-hydroxycyclohexyl)(2-naphthyl)acety|]pvrrolidin-3-yl}carbarnate was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1q) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS m/z 437 [0536] In an analogous manner to Example 13, step 2, 1-[2-[(3S)-3-(methylamino)pyrrolidin-i-yli-1 -(2-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from tert-butyl {(3S)-1-[(1-hydroxycyclohexyl)(2-naphthyl)acetyl]pyrrolidin-3-yljcarbamate MS (ESI) m/z 353; HRMS: calcd for C23H32N2O + H, 353.25929; found (ESI, [M+HD, 353.2582. Example 204: 1-[2-[(3S)-3-aminopyrrolidin-1-yl]-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride [0537] !n an analogous manner to Example 1, step 1, iert-bu\\-\ {(3S)-1-ir(1-hydroxycyclohexyl)(2-naphthyl)acetynpyrrolidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1q) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS m/z 437 [0538] In an analogous manner to Example 1, step 2, 1 -[2-F.(3S)-3-aminopvrrolidin-1 -yl]-1 -(2-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from y -butyl {(3S)-1-[(1-hydroxycyclohexyl)(2-naphthyl)acetyl]pyrrolidin-3-yl}carbamate MS (ESI) m/z 339; HRMS: calcd forC22H3oN20 + H, 339.24364; found.(ESI, [M+H]+), 339.2441. Example 205: 1-r2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-1-[2-naphthylethyl]cyclohexanol dihydrochloride -193- WO 2005/037279 PCT/US200-I/0J37J2 [0539] In an analogous manner to Example 36, 1-[2-[(3S)-3-(dimethylamino)pyrrolidin-1 -yl]-1 -(2-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[2-[(3S)-3-aminopyrrolidin-1-yl]-1-(2-naphthyl)ethyl]cyclohexanol (See Example 204). MS (ES) m/z 367.1; HRMS: calcd for C24H34N2O + H, 367.27494; found (ESI, [M+HD, 367.2729. Example 206: 1-[2-r(3S)-3-(methylamino)pvrrolidin-1-yl1-1-0- naphthyl)ethyllcyclohexanol dihydrochloride [0540] In an analogous manner to Example 1, step 1, y -butyl [(3S)-1-f(1-hydroxycyclohexyl)(1-naphthyl)acetyl]pvrrolidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)(1-naphthyl)acetic acid (Reference Example 1-e) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z453.2 -194- WO 2005/037279 PCT/US2004/033732 [0541] In an analogous manner to Example 13, step 2, 1-[2-[(3S)-3-(methylamino)pvrrolidin-1-yl1-i-fi-naphthyl)cthyl1cyclohexanol dihydrochloride was prepared from te/1-butyl {(3S)-1-[(i-hydroxycyclohexyl)(1-naphthyl)acetyl]pyrrolidin-3-yljcarbamate MS (ESI) m/z 353; HRMS: calcd for C23H32N2O + H, 353.25929; found (ESI, [M4H]+), 353.2589. Example 207: 1-[2-[(3S)-3-aminopvrrolidin-1-yll-1-(1-naphthynethyl]cyclohexanol dihydrochloride [0542] In an analogous manner to Example 1, step 1, y -butyl ((3S)-1-[(1-hydroxycyclohexyl)(1-naphthyl)acetylipvrrolidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)(1-naphthyl)acetic acid (Reference Example 1e) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 453.2 [0543] In an analogous manner to Example 1, step 2, 1-[2-f/(3.S)-3-aminopvrrolidin-1-yl1-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from fert-butyl {(3S)-1-[(1-hydroxycyclohexyl)(1-naphthyl)acetyl]pyrrolidin-3-yl}carbamate MS (ESI) m/z 339; HRMS: calcd for C22H30N2O + H, 339.24364; found (ESI, [M+H]+), 339.2421. Example 208: 1-[2-[(3S)-3-(dimethylamino^pyrrolidin-1-yl]-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride -195- WO 2005/037279 PCT/US2004/033732 [05441 In an analogous manner to Example 36, 1-[2-[(3S)-3-(dimethylamino)pyrrolidin-1 -yl]-1 -0 -naphthyl)ethyllcyclohexanol dihydrochloride was prepared from 1-[2-[(3S)-3-aminopyrrolidin-1-yl]-1-(1-naphthyl)ethyl]cyclohexanol (See Example 207). MS (ES) m/z 367.1; HRMS: calcd for C24H3,.N2O + H, 367.27494; found (ESI, [M+H]*), 367.275. Example 209: 1 -1 -[4-(Benzyloxy)-3-chlorophenyl1-2-[(3S)-3-(methylamino)pyrrolidin-1 - yl]ethyl)cyclohexanol dihydrochloride [0545] In an analogous manner to Example 1, step 1, tert-butyl ((3S)-1-f[4-(Benzyloxy)-3-chlorophenvH(1-hydroxycyclohGxyl)acetynpyrrolidin-3-yl)carbamate was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetic acid (Reference Example 1eee) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 543.0 [0546] In an analogous manner to Example 13, step 2, 1-0 -[4-(benzyloxy)-3-chlorophenyl]-2-[(3S)-3-(methylamino)pyrrolidin-1-yl1ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl {(3S)-1-[[4-(benzyloxy)-3-chlorophenyl](1-hydroxycyciohexyl)acetyl]pyrrolidin-3-yl}carbamate MS (ES) m/z 443.1; HRMS: calcd for C25H35CIN2O2 + H, 443.24653; found (ESI, [M+H]+), 443.2449. Example 210: 1-(2-r(3S)-3-aminopvrrolidin-1-yn-1-[4-(Benzyloxy)-3-chlorophenyliethyDcyclohexanol dihydrochloride -195- WO 2005/OJ7279 PCT/IJS2O04/033732 [0547] In an analogous manner to Example 1, step 1, tert-butyl l(3S)-1-f[4-fBenzyloxy)-3-chlorophenyl1(1-hydroxycyclohQxyl)acetyl1pvrrolidin-3-yl)carbamate was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetic acid (Reference Example 1eee) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 543. [0548] In an analogous manner to Example 1, step 2. 1 -(2-[(3S)-3-aminopyrrolidin-1 -yl1-1-[4-(Benzyloxy)-3-chlorophenyl1ethyl)cyclohexanol dihydrochloridc- was prepared from tert-buty! {(3S)-1-[[4-(benzyloxy)-3-chlorophenyl]{1- hydroxycyclohexyl)acetyl]pyrrolidin-3-yl}carbamate MS (ES) m/z 429.0; HRMS: calcd for C25H33CIN2O2 + H, 429.23088; found (ESI, [M+H]+), 429.232. Example 211: 1-0-[4-(Benzyloxy)-3-chloroDhenyl]-2-[(3S)-3-(dimethylamino)pyrrolidin-1- ..I1~»u..n~,. —i_u 1 J:U.,-J, i_i-r;^/- yl|t;u iylfv-.y\>iui icrAai IUI Oil iy0nJurn0riu6 -197- WO 2005/037279 PCT/IJS2004/033732 [0549] In an analogous manner to Example 36, 1-{i-[4-(benzyloxy)-3-chlorophenylj-2-[I3SK3-(dimethylamino)pvrrolidin-1-yl)ethyl)cyclohexanol dihydrochloride was prepared from ^1-{2-[(3S)-3-aminopyrrolidin-1-yl]-1-[4-(benzyloxy)-3- chlorophenyl]ethyl}cyclohexanol_(See Example 210). MS (ES) m/z 457.0; HRMS: calcd for C27H37CIN2O2 + H, 457.26218; found (ESI, [M+H]+), 457.2636. Example 212: 1-0-[4-(bcnzyloxv)phenyl]-2-[(3S)-3-(mcthylamino)pyrrolidin-1-yl]ethyl)cyclohexanol dihydrochloride [0550] In an analogous manner to Example 1, step 1, tert-butyl ((3S)-1-f[4-(Benzyloxy)phenyl]0-hydroxycyclohexyl)acetyliPvrrolidin-3-yl)carbamate was prepared from (4-benzyloxyphenyl)(1-hydroxycyclohexyl)acetic (Reference Example 1n) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 509.0 [0551] In an analogous manner to Example 13, step 2, 1 -1 -[4-(Benzyloxy)phcnyn-2-[(3S)-3-fmethylamino)pyrrolidin-1 -yl]ethyl]cyclohexanol dihydrochloride was prepared from rerf-butyl {(3S)-1-[[4-(benzyloxy)phenyl](1-hydroxycyclohexyl)acetyl]pyrrolidin-3-yl}carbamate MS (ES) m//409.1; HRMS: calcd for C2sH35N2O- + H, 409.28550; found (ESI, [M+H]*), 409.2841 Example 213: 1-(2-[(3S)-3-aminopyrrolidin-1-yll-1-[4 (Benzyloxy)phenyl]ethyl)cyclohexanol dihydrochloride -198- WO 2005/0J7279 PCT/US20(I4/03.*7.12 [0552] In an analogous manner to Example 1, step 1, y -butyl ((3S)-1-[[4-(Benzyloxy)phenyl1(1-hydroxycyclohexyl)acetyl]pyrrolidin-3-yl)carbamate was prepared from (4-benzyloxyphenyl)(1-hydroxycyclohexyl)acetic_(Reference Example 1n) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 509.0 [0553] In an analogous manner to Example 1, step 2, 1 -(2-[(3S)-3-aminopyrrolidin-1 -yl]-1 -[4-(Benzyloxy)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl {(3S)-1-[[4-(benzyloxy)phenyl](1-hydroxycyclohexyl)acetyl]pyrrolidin-3-yl}carbamate MS (ES) m/z395.1; HRMS: calcd for C25H34N2O2 + H, 395.26985; found (ESI, [M+H]4), 395.2696. Example 214: 1-0-[4-(Benzyloxy)pheriyn-2-[(3S)-3-(dimethylamino)pvrrolidin-1- yliethyl)cyclohexanol dihydrochloride -199- WO 2005/037279 PCT/US200-I/0337.12 [0554] In an analogous manner to Example 36, 1-(i-[4-(Benzyloxy)Dhenyl]-2-[(3SV3-(dim&lhylamino)pvrrolidin-1-yl]et_hyl)cyclohexanoj_djhydrochloride was prepared from, 1-{2-[(3S)-3-aminopyrrolidin-1 -yl]-1 -[4-(benzyloxy)phenyl]cthyl}cyclohexanol (See Example 213). MS (ES) m/z 423.1; HRMS: calcd for C27H33N2O2 + H, 423.30115; found (ESI, [M+H]4), 423.302 Example 215: 1-{2-[(3S)-3-(methylamino)pyrrolidin-1-yl1-1-[3- (trifluoromethoxy)phenyl]ethyl)cyclohexano) dihydrochloride [0555] In an analogous manner to Example 1, step 1, y -butyl ((3S)-1-((1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl1acetyl)pyrrolidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1f) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 487.0 [0556] In an analogous manner to Example 13, step 2, 1-(2-[(3S)-3-(methylamino)pvrrolidin-1-yl1-1-[3-(trifluorornethoxy)phenyl]ethyl}cyclohexanol dihydrochloride was prepared from tert-butyl ((3S)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl)carbamate MS (ES) m/z 387.1; HRMS: calcd for C2oH29[3N202 + H, 387.22594; found (ESI, [M+H]*), 387.2255. Example 216: 1-(2-[(3S)-3-aminopyrrolidin-1-yl]-1-[3-(trifluoromethoxy'iphenyliethyl)cyclohexanol dihydrochloride -200- WO 2005/037279 PCT/US200-I/0337J2 [0557] In an analogous manner to Example 1, step 1, tort-butyl ((3S)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl1acetyl)Pvrrolidin-3-yl)carbamnte was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1f) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 487.0 [0558] In an analogous manner to Example 1, step 2, 1-(2-[(3S)-3-am!nopyrrolidin-1-yl1-1-[3-(trifluoromethoxy^phenyl]ethyl)cyclohexanol dihydrochloride was prepared from fert-butyl ((3S)-1 -{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl)carbamate MS (ESI) m/z 373; HRMS: calcd for C19H27[3N2O2 + H, 373.21029; found (ESI, [M+H]+), 373.2106. Example 217: 1-(2-f[3S)-3-(dimethylamino)pvrrolidin-1-yll-1-[3-(trifluoromethoxy)phenyHethyl)cyclohexanol dihydrocNpridG -201- WO 2005/037279 PCT/L1S2OO4/0337J2 [0559,1 In an analogous manner to Example 36, 1-(2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl1-1-[3-ftritluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from, 1-{2-[(3S)-3-aminopyrrolidin-1-yl]-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol (See Example 216). MS (ESI) m/z401; HRMS: calcd for C21H3i[3N2C>2 + H, 401.24159; found (ESI, [M+H]+), 401.2413. Example 218: 1-(2-[(3R)-3-(methylamino)pyrrolidin-1-yl]-1-[3-(trifluoromethoxy)phenyl1ethyl)cyclohexanol dihydrochloride [0560] In an analogous manner to Example 1, step 1, y -butyl ((3/7)-1-((1-hydroxycyclohexyl)[3-(trif!uoromethoxy)phenyHacetyl)pvrrolidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1f) and (3R)-(-)-3-(tert-hntoxycarhony!amino)pyrro!!d!ne. MS (ES) rrJz487.0 [0561 ] In an analogous manner to Example 13, step 2, 1-(2-[(3fi)-3-(methylamino)pvrrolidin-1-yl1-1-[3-(trifluoromGthoxv)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from y -butyl ((3R)-1-{(1-hydroxycyc!ohGxy!)[3-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl)carbamate MS m/z387; HRMS: calcd for C20H29[3N2O2 + H, 387.22594; found (ESI, [M+H]+), 387.225. Example 219: 1-(2-[(3fl)-3-(dimethylamino)pyrrolidin-1-yl]-1-[3-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride -202- WO 2005/037279 PCT/IJS2004/0J37J2 [0562] In an analogous manner to Example 36, 1-(2-[(3ffl-3-(dimethylamino)pyrrolidin-1 -yll-1 -[3-(trifluoromethoxy)phenyl1ethyl)cyclohexanol dihydrochloride was prepared from, 1 -{2-[(3/T>)-3-(methylamino)pyrrolidin-1 -yl]-1 - [3(trifluoromethoxy)phenyl]ethyl}cyclohexanol (See Example 218). MS (ESI) m/z401; HRMS: calcd for C?-,H3,[3N2O2 + H, 401.24159; found (ESI, (M+H]+), 401.2397. Exampie 220: i -(2-[(3S)-3-(methylamino)pyrroiidin-1 -yl]-1 -[3-(trifluoromethyQphenvUethyl]cyclohexanol dihydrochloride [0563] In an analogous manner to Example 1, step 1, te/1-butyl ((3S)-1-((1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetyl)pvrrolidin-3-yl)carbamate was prepared from (1-hydroxycyc!ohexyl)[3-(trifluoromethyl)phenyl]acetic acid (Reference Example 1m) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z471.1 -203- WO 20O5/0J7279 PCT/US200-I/033732 [0564] In an analogous manner to Example 13, step 2, 1-(2-[(3S)-3-(met^ylamino)pyrrolidin-1 -yl]-1 -[3-(trif luoromethyl)phenvHethyl)cyclohexanol dihydrochloride was prepared from tert-butyl ((3S)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl)carbamate MS (ESI) m/z 371; HRMS: calcd for C20H29[3N2O + H, 371.23102; found (ESI, [M+HD, 371.2293. Example 221: 1-(2-[(3SV-3-aminopyrrolidin-1-yl]-1-[3-(trifluoromethyhphenyl]ethyljcyclohexanol dihydrochloride [0565] In an analogous manner to Example 1, step 1, tert-butyl ((3S)-1-(0-hydroxvcyclohexyl][3-(trifluoromethyl)phenyl]acetyl)pyrrolidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethyl)pheny!]acetic acid (Reference Example 1m) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 471.1 [0566] In an analogous manner to Example 1, step 2, 1 -(2-[(3S)-3-aminopyrrolidin-1 -yl]-1-[3-(trifluoromethyl)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from y -butyl ((3S)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl)carbamate MS (ESI) m/z 357; HRMS: calcd for CgH^^O + H, 357.21537; found (ESI, [M+H]+), 357.2139. Example 222: 1-(2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-1-[3-(trifluoromethvQphenvHethylcyclohexanol dihydrochloride -204- W'O 2005/037279 PCT/US2OO4/OJJ7J2 [0567] In an analogous manner to Example 36, 1-(2-[(35)-3-(dimethylamino)pyrrolidin-1 -vH-1 -[3-(trifluoromethyl)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from, 1 -{2-[(3S)-3-aminopyrrolidin-1 -yl]-1 -[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol (See Example 221). MS (ES) m/z 385.1; HRMS: calcd for C21H31[3N2O + H, 385.24667; found (ESI, [M+H]*), 385.2454. Example 223: 1-(2-r(3ffl-3-(methylamino)pvrrolidin-1-yl]-1-[3-(trifluoromethyl)phenyl1ethyl)cyclohexanol dihydrochloride [0568] In an analogous manner to Example 1, step 1, tert-butyl ((3R)-1-(0-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetyl)pyrrolidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trif!uoromethyl)phenyl]acetic acid (Reference Example 1m) and (3R)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 471.0 -205- WO 2005/037279 PCT/US2OO4/033732 [0569] In an analogous manner to Example 13, step 2, 1-(2-[(3ff)-3_-(me-:y\ylamino)pvrrolidin-1-yl]-1-[3-(trifluoromGthyl)phonyl1ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl ((3R)-1-{(1-hydroxycyclohexyl)[3-(trifluoromeihyl)phenyl]acetyl}pyrrolidin-3-yl)carbamate MS (ES) m/z 371.1; HRMS: calcd for C2oH29[3N20 + H, 371.23102; found (ESI, [M+H]+), 371.2296. Example 224: 1-(2-[(3R)-3-aminopyrrolidin-1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl)cyclohexanol dihydrochloride [0570] In an analogous manner to Example 1, step 1, tert-butyl ((3f?)-1-(0-hydroxvcyclohexyl][3-(trifluoromethyl)phenyl1acetyl)pvrrolidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetic acid (Reference Example 1m) and (3R)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 471.0 [0571] In an analogous manner to Example 1, step 2, 1 -(2-[(3R)-3-aminopvrrolidin-1 -yl1-1-[3-(trifluoromethyl)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl ((3f?)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl)carbamate MS (ES) m/z 357.1; HRMS: calcd for Ci9H27[3N2O + H, 357.21537; found (ESI, [M+H]*), 357.2154. Example 225: 1-(2-[(3/:?)-3-(dimethylamino)pvrrolidin-1-yl]-1-[3-(trifluoromethyl)phenyl1ethyl)cyclohexanol dihydrochloride -206- WO 2005/037279 PCT/US2004/033732 [0572] In an analogous manner to Example 36, 1-(2-[(3ffl-3-(dirnethylamino)pyrrolidin-1 -yl]-1 -[3-(trifluoromethyl)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from, 1-{2-[(3H)-3-aminopyrrolidin-1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol_(See Example 224). MS (ESI) m/z385; HRMS: calcd for C21H31[3N2O + H, 385.24667; found (ESI, [M+HD, 385.2454. Reference Example 2-a: Aikviation Reaciion: Preparation of Acid intermediates [0573] A solution of diisopropylamine 0.80 mL, 12.9 mmol) in dry tetrahydrofuran (6 mL) under nitrogen was cooled to -78 CC and treated dropwise with a solution of n-butyl]ithium (2.4 M in hexanes, 5.4 mL, 12.9 mmol). The resulting solution was warmed to 0 °C and stirred for 15 min. The solution was re-cooled to -78 °C and treated, via cannula, with a solution of 3-chlorophenylacetic acid 0.0 g, 5.9 mmol) in tetrahydrofuran (6 mL). The reaction was then allowed to warm to 25 °C where it was stirred for 45 minutes and was then re-cooled to -78 CC. Cyclopentyl bromide (0.76 mL, 7.1 mmol) was then added via syringe, and the resulting mixture was stirred at -78 °C for 1 hour. The reaction mixture was allowed to warm to room temperature and then stirred overnight. The reaction was then quenched by the addition of a saturated aqueous solution of ammonium chloride, and the tetrahydrofuran was removed in vacuo. The resulting residue was dissolved in a 2N aqueous solution of sodium hydroxide (30 mL) and washed with ethyl acetate 0x15 mL). The aqueous layer was then acidified to pH = 1 with the addition of a 2 N aqueous solution of hydrochloric acid. The product was extracted with ethyl acetate (3 x 15 mL), and the combined organic extracts were dried over magnesium sulfate, concentrated in vacuo and the product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% EtOAc/hexane to 40% EtOAc/hexane) to -207- W'O 2005/0J7279 PCT/US2004/033732 yleld 1.08 g (79%) (3-chlorophenyl)(cycloDentyl)acetic acid as a clear oil. HRMS: calcd for C°;-3H15CIO2 - H, 237.06823; found (ESI, [M-H]-), 237.0682 ss)ln an analogous manner, (3-chlorophenyl)(cyclohexyl)acetic acid was prepared from 3-chlorophenylacetic acid and cyclohexylbromide. HRMS: calcd for C14H17CIO2 -H, 251.0817; found (ESI, [M-H]"), 251.0849. tt) In an analogous manner, (3-chlorophenyl)(cycloheptyl)acetic acid was prepared from 3-chlorophenylacetic acid and cycloheptylbromide. HRMS: calcd for ClsHi9CIO2-H, 265.0974; found (ESI, [M-H]"), 265.0985. uu)ln an analogous manner, (3-chlorophenyl)(2-hydroxvcyclohexyl]acetic acid was prepared from 3-chlorophenylacetic acid and cyclohexene oxide. HRMS: calcd for C14H17C!O3-H, 267.0766; found (ESI, [M-H]"), 267.0779 Example 226: 1-[2-(3-chlorophenvr)-2-cyclopentylethynpiperazine dihydrochloride [0574] In an analogous manner to Example 1, step 1, tert-butyl 4-[(3-chlorophonylKcyclopentyQacetynpiperazine-i-carboxylate was prepared from (3-chlorophenyl)(cyclopentyl)acetic acid (Reference Example 2-a) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C-H31CIN2O3+H, 407.2123; found (ESI, [M+H]+), 407.2094. -208- WO 2005/037279 PCT/U$2004/033732 [0575] In an analogous manner to Example 1, step 2, 1 -[2-(3-chlorophenyl)-2-cycLoj^entylethyl]piperazine dihydrochloride was prepared from fe/1-butyl 4-[(3-chlorophenyl)(cyclopentyl)acetyl]piperazine-1-carboxylate HRMS: calcd for Ci7H2r,CIN2 + H, 293.17845; found (ESI, [M+H]+), 293.1776 Example 227: 1 -[2-(3-chlorophenyl)-2-cyclopentylethyn-4-methylpipera7-ine dihydrochloride [0576] In an analogous manner to Example 24, 1 -[2-(3-chiorophenyl)-2-cyclopentylethyn-4-methylpiperazine dihydrochloride was prepared from, 1-[2-(3-chlorophenyl)-2-cyclopentylethyl]piperazine (See Example 226). MS (ES) m/z 307.2; HRMS: calcd for C18H27CIN2 + H, 307.19410; found (ESI, [M+H]*), 307.1935. Example 228: 1 -[2-(3-chlorophenyl)-2-cyclopentylethyn-A/-methylpiperidin-4-amine dihydrochloride -209- WO 2005/037279 PCT/US2OO4/0JJ732 [0577] In an analogous manner to Example 1, step 1, y -butyl 0-[3-chlgr$iphenyl)(cyclopentyl]acGtyl1pipericlin-4-yl)carbamate_was prepared from (3-chlorophenyl)(cyclopentyl)acetic acid (Reference Example 2-a) and 4-N-Boc-aminopiperidine. HRMS: calcd for C23H33CIN2O3+H, 421.2280; found (ESI, [M+H]+), 421.2269. [0578] In an analogous manner to Example 13, step 2, 1 -[2-(3-chlorophenyl)-2-cyclopentylethyl1-A/-methylpiperidin-4-amine dihydrochloride was prepared from tert-butyl {1-[(3-chlorophenyl)(cyclopentyl)acetyl]piperidin-4-yl}carbamate MS (ES) m/z 321.2; HRMS: calcd for C19H29CIN2 + H, 321.20975; found (ESI, [M+H]+). 321.2088. Example 229: 1-[2-(3-ch.ioroph6nyl)-2-cyc!operiN-!ethyli-A/./V-dimethylpiperidin-4-amine dihydrochloride [0579] In an analogous manner to Example 36, 1 -[2-(3-chlorophenyl)-2-cyclopentylethyn-A/.A/-dimethylpiperidin-4-amine dihydrochloride was prepared from, 1-[2-(3-chlorophenyl)-2-cyclopentylethyl]-A/-methylpiperidin-4-amine.(See Example 228). MS(ES) m/z 335.2; HRMS: calcd for C2oH31CIN2 + H, 335.22540; found (ESI, [M+H]+), 335.2243. Example 230: 1-[2-(3-chlorophenyl)-2-cyclohexylethynpiperazine dihydrochloride -210- WO 2005/037279 PCT/US2004/033732 [0580J In an analogous manner to Example 1, step 1, tert-butyl 4-[(3-chloiophenylHcyclohexynacetylipiperazine-i-carboxylate was prepared from (3-chlorophenyl)(cyclohexyl)acetic acid (Reference Example 2-b) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C23H33CIN2O3+H, 421.2280; found (ESI, [M+H]+), 421.2261. [0581] In an analogous manner to Example 1, step 2, 1 -[2-(3-chlorophenyl)-2-cyclohexylethyl]piperazine dihydrochloride was prepared from tert-butyl 4-[(3-chlorophenyl)(cyclohexyl)acetyl]piperazine-1-carboxylate HRMS: calcd for C18H27CIN2 + H, 307.19410; found (ESI, [M+H]+)t 307.1943. Example 231: 1 -[2-(3-chlorophenyl)-2-cyclohexylethyll-4-methylpiperazine dihydrochioride [0582] In an analogous manner to Example 24, 1 -[2-(3-chlorophenyl)-2-cyclohexylethyll-4-methylpiperazine dihydrochloride was prepared from, 1-[2-(3-chlorophenyl)-2-cyclohexylethyl]piperazine (See Example 230). MS (ES) m/z 321.2; HRMS: calcd for C19H29CIN2 + H, 321.20975; found (ESI, [M+H]+), 321.2108. Example 232: 1 -[2-(3-chlorophenyl)-2-cyclohexylethyn-A/-methylpiperidin-4-amine dihydrochloride -211- WO 2005/037279 PCT/US2004/033732 [05831' In an analogous manner to Example 1, step 1, fe/t-butyl 0-[(3-chlorophenylVcyclohexyl)acetyl]piperidin-4-yl^carhamate was prepared from (3-chlorophenyl)(cyclohexyl)acetic acid (Reference Example 2-b) and 4-N-Boc-aminopiperidine. HRMS: calcd for C24H35CIN2O3+H, 435.2436; found (ESI, [M+H]*), 435.2422. [0584] In an analogous manner to Example 13, step 2, 1 -[2-(3-chlorophenyl)-2-cyclohexylethyl1-ft/-methylptperidin-4-amine dihydrochloride was prepared from tert-butyl {1-[(3-chlorophenyl)(cyclohexyl)acetyl]piperidin-4-yl}carbamate MS (ES) m/z335.3; HRMS: calcd for C20H3iCIN2 + H, 335.22540; found (ESI, [M+H]+), 335.2245. Example 233: 1-[2-(3-chlorophenyn-2-cyclohexylethyll-A/,/\/-dimethylpiperidin-4-amine dihydrochloride [0585] In an analogous manner to Example 36, 1 -[2-(3-chlorophenyl)-2-cyclohexylethyH-N,N-dimethylpiperidin-4-amine dihydrochloride was prepared from, 1-[2-(3-chlorophenyl)-2-cyclohexylethyl]-A/-methylpiperidin-4-amine (See Example 232). HRMS: calcd for C21H33CIN2 + H, 349.24105; found (ESI, [M+H]+), 349.2422. Example 234: H2-(3-chlorophenyO-2-cycloheptylethyl1piperazine dihydrochloride -212- W'O 2005/037279 PCT/US2004/033732 [0586] In an analogous manner to Example 1, step 1, tert-butyl 4-K3-chlorophenyl)(cycloheptyl)acetyl]piperazine-1-carboxylatG was prepared from (3-chlorophenyl)(cycloheptyl)acetic acid (Reference Example 2-c) and tert-butyl 1-piperazinecarboxylate. MS m/z 379 [0587] In an analogous manner to Example 1, step 2, 1 -[2-(3-chlorophenyl)-2-cycloheptylethylipiperazine dihydrochloride was prepared from y -butyl 4-[(3-chlorophenyl)(cycloheptyl)acetyl]piperazine-1-carboxylate MS (ES) m/z 321.2; HRMS: calcd for C19H29CIN2 + H, 321.20975; found (ESI, [M+H]+), 321.2105. Example 235: 1 -[2-(3-chlorophenyl-2-cyclohepMethyl1-4-methylpiperazine dihydroc'nioride [0588] In an analogous manner.to Example 24, 1 -[2-(3-chlorophenyl)-2-cycloheptylethyli-4-methylpiperazine dihydrochloride was prepared from, 1-[2-(3-chlorophenyl)-2-cycloheptylethyl]piperazine_(See Example 234). MS (ES) m/z 335.2; HRMS: calcd for C2oH3iCIN2 + H, 335.22540; found (ESI, [M+H]+), 335.2253. Example 236: 1 -[2-(3-chlorophenyl)-2-cycloheptylethyn-A/-methylpiperidin-4-amine dihydrochloride -213- WO 2005/037279 F>CT7US200-»/033732 [0589] In an analogous manner to Example 1, step 1, /ert-butyl 0-[(3-chlorophenyl)(cycloheptyl)acetyllpiperidin-4-yl)carbamate was prepared from (3-chlorophenyl)(cycloheptyl)acetic acid (Reference Example 2-c) and and 4-N-Boc-aminopiperidine. MS m/z449 [0590] In an analogous manner to Example 13, step 2, 1 -[2-(3-chlorophenyl)-2- cycloheptylethyl1-A/-methylpiperidin-4-amine dihydrochloride was prepared from tert- butyl {1-[(3-chlorophcnyl)(cycloheptyl)acetyl]piperidin-4-yl}carbamate MS (ES) m/z349.2; HRMS: calcd for C21H33CIN2 + H, 349.24105; found (ESI, [M+H]+), 349.2412. Example 237: 1 -[2-(3-chlorophenyl)-2-cycloheptylethyl1-A/.A/-dimethylpiperidin-4-amine dihydrochloride [0591 ] In an analogous manner to Example 36, 1 -[2-[3-chlorophenvQ-2-cyclohepMethylVA/.M-dimethylpiperidin-4-amine dihydrochloride was prepared from, 1 -[2-(3-chlorophenyl)-2-cycloheptylethyl]-A/-methylpiperidin-4-amine (See Example 236). MS (ES) m/z 363.3; HRMS: calcd for C22H35CIN2 + H, 363.25670; found (ESI, [M+H]+), 363.2578. Example 238: 2-[1-(3-chlorophenyl-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride -214- \YL) 2005/037279 PCT/LS2O04/033732 [0592] Step 1: A solution of (3-chlorophenyl)(2-hydroxycyclohexyl)acetic acid (Reference Example 2-d) 0.25 g, 4.66 mmol), benzotriazol-1-yloxy1ris(dimethylaminop)phosphonium hexafluorophosphate (3.1 g, 7.0 mmol), and tert-butyl 1-piperazinecarboxylate (0.87 g, 4.66 mmol) in methylene chloride 02 mL) was treated with triethylamine (0.98 mL, 7.0 mmol). The reaction was stirred at 25 CC for 16 h, after which time the solvent was removed in vacuo and the product was purified via Biotage Horizon (FLASH 40 M, silica, gradient from 0% EtOAc/hexane to 25% EtOAc/hexane) to yleld 0.97 g (83%) the iactone, 3-i'3-chlorophenvi)hexahydro-1-benzofuran-2(3/-fron6 as a clear oil. HRMS: calcd for CKHi5C!O2 +H, 251.0861; found (ESI, [M+H]+), 251.0844. [0593] Step 2: A solution of 3-(3-chlorophenyl)hexahydro-1-benzofuran-2(3H)-one (540 mg, 2.19 mmol) in dry tetrahydrofuran (7 mL) was cooled to -78 °C under nitrogen and was treated dropwise with a solution of DiBAL 0.0 M in toluene, 3.07 mL, 3.07 mmol). The resulting solution was stirred at -78 °C for 2 h, after which time the reaction was treated a 1 M aqueous solution of sulfuric acid to dissolve precipitated salts. The reaction mixture was allowed to warm to room temperature and was partitioned between diethyl ether and water. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate, water, and brine and was dried over magnesium sulfate and concentrated in vacuo. The crude product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% EtOAc/hexane to 35% EtOAc/hexane) to yleld 0.38 g (69%) the lactol, 3-(3-chlorophenyl)octahydro-1-benzofuran-2-ol as a white foam. HRMS: calcd for C14H17CIO2-H, 251.0817; found (ESI, [M-H]'), 251.0835. [0594] Step 3: A solution of 3-(3-chlorophenyl)octahydro-1-benzofuran-2-ol 075 mg, 0.69 mmol) and tert-butyl 1-piperazinecarboxylate 028 mg, 0.69 mmol) in -215- WO 2005/037279 PCT/US200-I/033732 dichloroethane (3 mL) was treated with sodium trisacetoxyborohydride (220 mg, 1.04 mm'dt1) The reaction was allowed to stir at room temperature for 16 h. The reaction was then diluted with methylene chloride and washed with a saturated aqueious solution of ammonium chloride (3 times). The organic layer was dried over magnesium sulfate and concentrated in vacuo and the product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% EtOAc/hexane to 30% EtOAc/hexane). This material was dissolved in methanol (0.5 mL) and treated with a saturated methanolic solution of hydrochloric acid (0.5 mL) followed by diethyl ether. After crystallizing in the refrigerator for 16 h, the resulting solid was collected, washed with diethyl ether and dried in vacuo to yleld 250 mg (83%) 2-[1-(3-chlorophenyl)-2-piperazin-1-ylethyncyclohexanol dihydrochloride as a white solid. HRMS: calcd for C18H27CIN2O + H, 323.18901; found (ESI, [M+H]*), 323.1891. Example 239: 2-[2-(4-aminopiperidin-1 -yl)-1 -O-chlorophenylethvilcyclohexanol dihydrochloride [0595] In an analogous manner to Example 238, step 3 2-[2-(4-aminopiperidin-1 -yl-1 -(3-chlorophenylethyllcyclohexanol dihydrochloride was prepared from 3-(3-chlorophenyl)octahydro-1-benzofuran-2-ol (see Example 238, Step 2) and N-Boc-4-aminopiperidine. HRMS: calcd for C9H29CIN2O + H, 337.20467; found (ESI, [M+H]+), 337.2031. Example 240: 1-(2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethoxy)phenyl]ethyl)piperidin-4- ol hydrochloride -216- WO 2005/037279 PCT/US2004/033732 [0596] In an analogous manner to Example 1, step 1, 1 -((1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenvHacetyl)piperidin-4-ol was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and 4-hydroxypiperidine. MS (ES) m/z402.0 [0597] In an analogous manner to Example 1, step 2, 1 -(2-( 1 -hydroxvcyclohexyl)-2-[3- \ ti ii lUorOiiiciriOAv ;pilcil yl i on 1 ylfMipci iLiii i-t-v-'l iiyji UU! ilUllyjfa y»db [Jibpaicu nOiTi i"\V'" hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}piperidin-4-ol MS (ES) m/z 388.0; HRMS: calcd for C20H28[3NO3 + H, 388.20995; found (ESI, [M+H]+), 388.2103. Example 241: 1-[2-[4-(Benzyloxy)-3-chlorophenyl]-2-(1-hydroxycyclohexyl)ethyl]piDeridin-4-ol hydrochloride [0598] In an analogous manner to Example 1, step 1, 1-[[4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetyl]piperidin-4-ol was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetic acid_(Reforence Example 1-eee) and 4-hydroxypiperidine. MS (ES) m/z 458.0 [0599] In an analogous manner to Example 1, step 2, 1-[2-[4-(Benzyloxy)-3-chlorophenyl]-2-0 -hydroxycyclohexylethyl]piperidin-4-ol hydrochloride was prepared from 1 -[[4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetyl]piperidin-4-ol MS -217- WO 2005/037279 PCT/US200 -1/033732 (ES) m/z444.1; HRMS: calcd for C26H34CINO3 + H, 444.23055; found (ESI, [M+H]+), 444.^316. Example 242: 1-M-r4-(Benzyloxy)-3-chlorophenyl]-2-(4-methoxypiperidin-1-yl]ethvUcyclohexanol hydrochloride [0600] In an analogous manner to Example 1, step 1, 1 -[1 -[4-(Benzyloxy)-3-chlorophenyl]-2-(4-methoxypiperidin-1-yl)-2-oxoethyl1cyclohexanol was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetic acid (Reference Example 1eee) and 4-methoxypiperidine (Baker, W.R.; Fung, A.K.I, Kleinhart, H.D et. Al. J. Med. Chem. 1992, 35 00), 1722-1734.) MS m/z 379 [0601 ] In an analogous manner to Example 1, step 2, 1 -[1 -[4-(Benzyloxy)-3-chlorophenyl1-2-(4-methoxypiperidin-1 -yl)ethyl]cyclohexanol hydrochloride was prepared from 1 -[1 -[4-(benzyloxy)-3-chlorophenyl]-2-(4-methoxypiperidin-1 -yl)-2-oxoethyl]cyclohexanol HRMS: calcd for C27H36CINO3 + H, 458.24620; found (ESI, [M+H]+), 458.2443. Example 243:1-10 S)-2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl1ethyl)cyclohexanol dihydrochloride -218- WO 2005/037279 PCT/US2004/033732 [0602] Racemic tert-butyl 4-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl} piperazine-1-carboxylate (see Example 23, step 1) was dissolved in methanol at a concentration of approximately 50 mg/mL The resulting solution was injected onto the Supercritical Fluid Chromatography instrument with an injection yl]ume of 750 DL. The baseline resolved enantiomers, using the conditions described below, were collected. The enantiomeric purity of each enantiomer was determined under the same Supercritical Fluid Chromatography conditions using a Chiralpak AD-H 5u, 250 mm x 4.6 mm ID column at 2.0 mL/min flow rate using Analytical Supercritical Fluid Chromatography (Berger Instruments, Inc. Newark, DE USA). SFC Instrument: Berger MultiGram PrepSFC (Berger Instruments, Inc. Newark, DE 19702. Column: Chiralpak AD-H; 5u; 250mm L x 20mm ID (Chiral Technologies, Inc. Exton, PA, USA) Column temperature: 35°C SFC Modifier: 10% EtOH Flow rate: 50 mUmin Outlet Pressure: 100 bar Detector: UV at 220 nm tert-butyl 4-((2fl)-2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethoxy)phenyl1acetyl) piperazine-1 -carboxylate was isolated at peak 1. MS (ES) m/z 487.2; HRMS: calcd for C24H33[3N2O5 + H, 487.2442 + H; found (ESI, [M+H]+), 487.2428; [a]D25 = +23° (c = 0.00116G/ML, EtOH); -219- WO 2005/037279 PCT/US2004/033732 tert-i,:'Ay\ 4-((2S)-2-0-hydroxvcyclohexyl)-2-[3-(trifluoromethoxy)phenyl|acetyl) piperazine-1 -carboxylate was isolated at peak 2. MS (ESI) m/z 487; HRMS: calcd for C24H33[3N2O5 + H, 487.2442; found (ESI, [M+H]+), [a\D2S = -19° (c = 0.0112G/ML, MeOH). [0603] In an analogous manner to Example 1, step 2 1-f05)-2-piperazin-1-yl-1-[3- (trifluoromethoxy)phenyl1ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-{(2ff)-2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethoxy)phenyl]acetyl} piperazine-1 - carboxylate. MS (ES) m/z 373.2; HRMS: calcd for C19H27[3N2O2 + H, 373.21029; found (ESI, [M+H]+), 373.2094; [ojD25 = +2.2° (c = 0.0099G/ML. MeOH). Example 244: 1-(0 f7)-2-p;pcraz;r,-1-yl-1-[3-(trifluoromethoxy)pheiiyl]ethyl)cyclohexanol dihydrochloride [0604] In an analogous manner to Example 1, step 2 1 -(0 FD-2-piperazin-1 -yl-1 -[3- (trifluoromethoxy)phenyl1ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-{(2S)-2-0-hydrbxycyclohexyl)-2-[3-(trifluoromethoxy)phenyl]acetyl}piperazine-1- carboxylate (see Example 243). MS (ES) m/z 373.1; HRMS: calcd for C^yFaf^C^ + H, 373.21029; found (ESI, [M+HD, 373.2102. Example 245: 1-(1S)-2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride -220- WO 2005/037279 PCT/US2004/0JJ732 [0605] In an analogous manner to Example 24, 1-f0S)-2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from, 1- {(iS)-2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol (Soe Example 243). MS (ES) m/z 387.2; HRMS: calcd for C2oH29[3N202 + H, 387.22594; found (ESI, [M+H]+), 387.2249. Example 246: 1-10/7)-2-(4-methylpiperazin-1-yl-1-[3-(trifluoromethoxy)phenynethyl)cyclohexanol dihydrochloride [0606] In an analogous manner to Example 24, 1-(0fi)-2-(4-methylpiperazin-1-yl)-1-[3-(trifluorornethoxy)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from, 1-{0/3)-2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol (See Example 244). HRMS: calcd for C2oH29[3N202 + H, 387.22594; found (ESI, [M+H]"), 387.2269. Example 247: 1-n-(3'.4'-dichloro-1,1'-biphenyl-3-yl]-2-(4-methylpiperazin-1-yl)ethylicyclohexanol dihydrochloride -221- WO 2005/037279 PCT/US2004/033732 [0607] In an analogous manner to Example 24, 1 -[1 -(3'.4'-dichloro-i, 1 '-biphenyl-S-yl]-2-(4-methylpiperazin-1 -yl)ethylicyclohexanol dihydrochloride was prepared from 1-[1-(S'.A'-dichloro-i.r-biphenyl-S-yO^-piperazin-i-ylethyljcyclohexanol (see Example 135). MS (ESI) m/z 447; HRMS: calcd for C25H32CI2N2O + H, 447.19699; found (ESI, [M+H]+), 447.1979. Example 248: 1 -(2-piperazin-1 -yl-1 -[3'-(trifluoromethoxy)-1,1 '-biphenyl-3-yl]ethyflcyclohexanol dihydrochloride [0608] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'- {rifluoromethoxy-biphenyl-S-yl]^-d-hydroxycyclohexylethylipiperazine-i-carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-0- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 135, step 2) and 3-trifluoromethoxy phenyl boronic acid. [0609] In an analogous manner to Example 135, step 4 1 -(2-piperazin-1 -yl-1 -[31- (trifluoromethoxy)-1.1'-biphenyl-3-yl]ethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3'-trifluoromethoxy-biphenyl-3-yl)-2-0- hydroxycyclohexyl)ethyl]piperazine:1-carboxylate. MS (ESI) m/z 449; HRMS: calcd for C25H31[3N2O2 + H, 449.24159; found (ESI, [M+H]+), 449.2434. Example 249: 1 -(2-piperazin-1 -yl-1 -[4'-(trifluoromethylH. 1 '-biphenyl-3-yliethyl]cyclohexanol dihydrochloride -222- WO 2005/037279 PCT/US2OO4/O3J7J2 [0610] In an analogous manner to Example 135, step 3 tert-bu'.yl 4-(2-(4'- trifluoromethyl-biphenyl-S-yl)^-d-hydroxvcyclohexylethylipiDGrazine-i-carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 135, step 2) and 4-trifluoromethyl phenyl boronic acid. [0611] In an analogous manner to Example 135, step 4 1-(2-piperazin-1-yl-1-[4'-(trifluoromethyl)-1.1'-biphenyl-3-yllethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(4'-trifluoromethyl-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 433; HRMS: calcd for C25H31[3N2O + H, 43324667; found (ESI, [M+H]+), 433.2474. Example 250: 1 -[1 -(3',4'-dimethoxy-1.1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0612] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3',4'-dimethoxy-hiphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethylipiperazine-1-carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 135, step 2) and 3'.4'-dimethoxy phenyl boronic acid. [0613] In an analogous manner to Example 135, step 4 1-[1-(3'.4'-dimethoxy-i .1'-biphenyl-3-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3\4'-dimethoxy-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 425; HRMS: calcd for C26H36N2O3 + H, 425.28042; found (ESI. [M+HJ+), 425.2801. -223- WO 2005/037279 PCT/US20O4/0J37J2 Example 251: 1 -0 -f6-methoxy-3'-(trifluoromethoxy)-1.1 '-biphenyl-3-yl]-2-piperazin-1 - ylethyl)cyclohexanol dihydrochloride [0614] Step 1: In an analogous manner to Example 1, step 1 tert-butyl 4-[(3-bromo-4-rnethoxyl)henyl)(1-hydroxycyclohexyl)acetyl1piperazine-1-carboxylate was prepared from (3-bromo-4-methoxyphenyl)(1-hydroxycyclohexy!)acetic acid (Reference Example l-l) and rert-butyl 1-piperazinecarboxylate. [0615] Step 2: In an analogous manner to Example 135, step 2 tert-butyl 4-[2-(3- bromo. 4-methylxyphenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from y -butyl 4-[(3-bromo-4-methoxyphenyl)0- hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. [0616] Step 3: In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(1-hydroxy-cyclohexyl)-2-(6-methoxy-3'-trifluoromethoxy-biphenyl-3-yl)-ethyl1-piperazine-1-carboxylate was prepared from y -butyl 4-[2-(3-bromo,4-methoxyphenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate and 3-trifluoromethoxy phenyl boronic acid. [0617] Step 4: In an analogous manner to Example 135, step 4 1-0-f6-methoxy-3'-(trifluoromethoxy)-1.1'-biphenyl-3-yl]-2-piperazin-1-ylethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(1-hydroxy-cyclohexyl)-2-(6-methoxy-3'-trifluoromethoxy-biphenyl-3-yl)-ethyl]-piperazine-1-carboxylate. MS (ESI) m/z 479; HRMS: calcd for C26H33[3N2O3 + H, 479.25215; found (ESI, [M+H]+), 479.2529. -224- WO 2005/037279 PCT/US2004/0JJ732 Example 252: 1-H-(3'.4'-dichloro-6-rnethoxv-1.1'-biphenyl-3-yl)-2-piperazin-1- ylethyUcyclohexanol dihydrochloride [0618] In an analogous manner to Example 135, step 3 tert-buty! 4-[2-(3',4'-dichloro-6- methoxy-1.r-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl1piperazine-1-carboxylate was prepared from fert-butyl-4-[2-(3-bromo,4-methoxyphenyl)-2-0- hydroxycyc!ohexy!)ethy!]piperazine-1-carboxy!ate (see Example 251, step 2) and 3,4-dichlorophenyl boronic acid. MS m/z 563; HRMS: calcd for C30H40CI2N2O4, 562.2365; found (ESI, [M+H]+), 563.2471. [0619] In an analogous manner to Example 135, step 4 1 -f1 -(3'.4'-dichloro-6-methoxy- 1.1'-biphenyl-S-yl^-piperazin-i-ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3',4'-dichloro-6-methoxy-1,1 '-biphenyl-3-yl)-2-0 - hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 463; HRMS: calcd for C25H32CI2N2O2 + H, 463.19191; found (ESI, [M+H]+), 463.1933. Example 253: 1-0-f6-methoxy-4'-(trifluoromethyl)-1,1'-biphenyl-3-yl]-2-piperazin-1- ylethyDcyclohexanol dihydrochloride -225- WO 2005/037279 PCT/US2U04/033732 [0620] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(4'- trifluorornethyl-6-rnethoxv-1.1'-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]Diperazine-1-carboxylate was prepared from tert-butyl-4-[2-(3-bromo,4-methoxyphenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 251, step 2) and 4-trifluoromethyl phenyl boronic acid. [0621] In an analogous manner to Example 135, step 4 l-0-f6-methoxy-4'- (trifluoromethyl)-1,1'-biphenyl-3-yl1-2-piperazin-1-ylethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(4'-trifluoromethyl-6-methoxy-1,1'-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 463; HRMS: calcd for C26H33[3N2O2 + H, 463.25724; found (ESI, [M+H]+), 463.256. Example 254: 1-[1-(6-methoxy-1.1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0622] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(6-methoxy-1.1'-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyllpiperazine-1-carboxylate was prepared from fert-butyl-4-[2-(3-bromo,4-methoxyphenyl)-2-(1-hydroxycyclohexyl)ethyl]piporazine-1-carboxylate (see Example 251, step 2) and phenyl boronic acid. [0623] In an analogous manner to Example 135, step 4 1 -[1 -(6-methoxy-1,1 '-biphenyl-3-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(6-methoxy-1,1 '-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. -226- WO 2005/037279 PCT/US2OO4/033732 MS (ES) m/z 395.2; HRMS: calcd for C25H34N2O2 + H. 395.2695; found (ESI, [M*H]+), 395.2693. Example 255: 1 -(1 -(3'.4'-dichloro-6-methoxy-1.1 '-biphenyl-3-yO-2-(4-methylpiperazin-1 - yl)ethyl]cyclohexanol dihydrochloride [0624] In an analogous manner to Example 24, 1-M-(3'.4'-dichloro-6-methoxy-1,1'- biphenyl-3-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(3',4'-dicri!oro-6-methoxy-1,1'-biphenyl-3-yl)-2-piperazin-1- ylethyljcyclohexanol (see Example 252). MS (ES) m/z 477.2; HRMS: calcd for C26H34CI2N2O2 + H, 477.20756; found (ESI, [M+H]+), 477.2064. Example 256: 1 -[ 1 -f6-methoxy-3'-(trifluoromethoxyV 1.1 '-biphenyl-3-yl]-2-(4-methvipiperazin-1 -yl]ethyllcyclohexanol riihydrochioride [0625] In an analogous manner to Example 24, 1 -[1 -f6-methoxy-3'-(trifluorornethoxy)-1,1 '-biphenyl-3-yl1-2-(4-methylpiperazin-1 -ynethyl]cyclohexanol dihydrochloride was prepared from 1 -[1 -(3'-trif luoromethoxy-6-methoxy-1,1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol (see Example 251). MS m/z 493; HRMS: calcd for C27H35[3N2O3 + H, 493.26780; found (ESI, [M+H]+), 493.2692. -227- W'O 2005/037279 PCT/US2O04/0J37J2 Example 257: 1-[1-f6-methoxy-4'-(trifluoromethyn-1.1'-biphenyl-3-yl]-2-(4-methylpiperazin-1 -ylethylicyclohexanol dihydrochloride [0626] In an analogous manner to Example 24, 1 -[1 -[6-methoxy-4'-(trifluoromethyl)-1,1'-biphenyl-3-yll-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride was prepared from 1 -[1 -(6-methoxy-4'-(trifluormethyl)-1,1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol (see Example 253). MS m/z 477; HRMS: calcd for C27H35[3N2O2 + H, 477.27289; found (ESI, [M+H]+), 477.2728. Example 258: 1-[0 fi)-1-(5-chlorothien-3-yl)-2-(4-methylpiperazin-1-yl)ethyllcyclohexanol dihydrochloride [0627] R- tert-butyl 4-[2-(5-chlorothien-3-yl)-2-0 -hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate was isolated from tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 144) by chiral column chromatography (Chiral OD-H, 100%acetonitrile, 16 ml/min). Elution time=9.9 min, (-) -CD [0628] In an analogous manner to Example 24, H0f?)-1-(5-chlorothien-3-yl)-2-(4-methylpiperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from the above isolated product. [ofo25 = -15° (c = 0.0092G/ML, MeOH); -228- WO 2005/037279 PCT/US200J/033732 MS (ESI) m/z 343.1627; HRMS: calcd for C17H27CIN2OS + H, 343.16108; found (ESI, [M^U), 343.1627. Example 259:1-[(iS)-1-(5-chlorothien-3-yl)-2-(4-nnethylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride [0629] S- tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethylipiperazine-1 -carboxylate was isolated from tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 144) by chiral column chromatography (Chiral OD-H, 100%acetonitrile, 16 ml/min). Elution time=11.8 min, (+)-CD [0630] In an analogous manner to Example 24, 1-f05)-1-(5-chlorothien-3-yl)-2-(4-methylpiperazin-1 -yl)ethylicyclohexanol dihydrochloride was prepared from the above isolated product. [^D25 = +16° (c = 0.0081 G/ML, MeOH); MS (ESI) m/z 343; HRMS: calcd for C17H27CIN2OS + H, 343.16108; found (ESI, [M+H]+)t 343.1606. Example 260 1 -[1 -(5-chloro-1 -benzothien-3-yl)-2-piperazin-1 -ylethyncyclohexanol [0631] Step 1: In an analogous manner to Example 1 step 1, tert-butyl 4-f(5-chloro-1-benzothien-3-yl)acctyl]piperazine-1 -carboxylate was prepared from 5- dihydrochloride -229- WO 2005/037279 PCT/DS20O4/0337J2 chlorobenzothiophene -3-acetic acid and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 395.0; HRMS: calcd for C19H23CIN2O3S, 394.1118; found (ESI, [M+H]+), 395.1201. [0632] Step 2: In an analogous manner to Example 141 step 3, tert-butyl 4-f(5-chloro- 1-benzothien-3-yl)-2-0-hydroxycyclohexyl)acetvHpiperazine-1-carboxylate was prepared from tert-butyl 4-[(5-chloro-1-benzothien-3-yl)acetyl]piperazine-1-carboxylate. [0633] Step 3: In an analogous manner to Example 135 step 2, tert-butyl 4-f(5-chloro-1 -benzothien-3-yl)-2-(1-hydroxvcyclohexyl]ethyllpiperazine-1 -carboxylate was prepared from tert-butyl 4-[(5-chloro-1-benzothien-3-yl)-2-(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. [0634] Step 4: In an analogous manner to Example 135 step 4, 1-[1-(5-chloro-1-benzothien-3-yl)-2-piperazin-1-ylethyl1cyclohexanol dihydrochloride was prepared from tert-butyl ' 4-[(5-chloro-1-benzothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate and isolated as a colorless powder. MS m/z 379; HRMS: calcd for C20H27CIN2OS + H, 379.15108; found (ESI, [M+H1+), 379.1607. Example 261 1 -[1 -0 -benzothien-2-yl)-2-piperazin-1 -ylethylicyclohexanoldihydrochloride [0635] Step 1: A solution of benzo[b]thiophene-2-carbaldehyde 0.0 g, 6.17 mmol) and carbon tetrabromide (3.1 g, 9.25 mmol) in methylene chloride (50 mL) was cooled to 0°C. A solution of triphenylphosphine (4.86 g, 18.3 mmol) in methylene chloride (20 mL) was added dropwise. After V* hour the solution was placed on a plug of silica gel and eluted with 20% ethyl acetate:hexane. Concentration of the eluent resulted in the -230- WO 2005/037279 PCT/US2004/033732 isolation o[1.3 g (67%) of 2^2.2-Dibromn-vinyl)-ben2o[b]thiophene as a yellow oil, which was used as such in the next step. [0636] Step 2: A 50 mL round bottom flask was charged with 2-(2,2-dibromo-vinyl)-benzo[b]thiophene 0.0 g, 3.17 mmol), y -butyl 1-piperazinecarboxylate (0.09 g, 4.76 mmol) and potassium hydroxide (0.71 g, 12.5 mmol). A solution of tetrahydrofuran:water (4:1) was added and the solution washeated to 70 °C for 18 hours. At the end of this time the solution was concentrated and the residue was diluted with a 2N aqueious solution of hydrochloric acid and extracted 3 times with ethyl acetate. The ethyl acetate was dried and concentrated and the residue subjected chromatography via Biotage (FLASH 40 M, silica, 60% ethyl acetate/hexane) to yleld 0.75 g (65%) of tert-butyl 4-[2-0 -benzothien-2-ylH -hydroxyethylipiperazine-1 -carboxylate as an off white solid. MS (ES) m/z 305.1; HRMS: calcd for C19H26N2O3S, 362.1664; found (ESI, [M+H]+), 361.1569. [0637] Step 3: In an analogous manner to Example 141 step 3, tert-butyl 4-f0-benzothien-2-yl)-2-(1-hydroxycyclohexyl)acetyl1piperazine-1-carboxylate was prepared from tert-butyl 4-[2-0-benzothien-2-yl)-1-hydroxyethyl]piperazine-1-carboxylate and HCOH oc ci i/"*H In +ho npvt cf<^n [0638] Step 4: In an analogous manner to Example 135, Step 2, tert-butyl 4-[0-benzothien-2-yl-2-(1-hydroxycyclohexyl)ethylipiperazine-1-carboxylate was prepared from tert-butyl 4-[0-benzothien-2-yl)-2-(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. [0639] Step 5: In an analogous manner to Example 135 step 4, 1-[1-0-benzothien-2-yl)-2-piperazin-1 -ylethyncyclohexanol dihydrochloride was prepared from tert-butyl 4-[0-benzothien-2-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 345.2; HRMS: calcd for C20H28N2OS + H, 345.20006; found (ESI, [M+H]+), 345.199. -231- WO 2005/037279 PCT/US2OO4/OJJ7J2 Example 262 1-(2-piperazin-1-yl-i-quinolin-3-ylethyl)cyclohexanol dihydrochloride [0640] Step 1: In an analogous manner to Example 261 step 1, 3-(2,2-Dibromo-vinyl)-quinoline was prepared from quinoline-3-carboxaldehyde. [0641] Step 2: In an analogous manner to Example 261 step 2, tert-butyl 4-(quinolin-3-ylacetyHpiperazine-i-carboxylate was prepared from 3-(2.2-Dibromo-vinyl)-quinolinft. MS m/z 356; HRMS: calcd for C20H25N3O3, 355.1896; found (ESI, [M+H]+)t 356.1963. [0642] Step 3: In an analogous manner to Example 261 step 3, tert-butyl 4-f(2-quinoline-3-yl)-2-0-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate was prepared from tert-butyl 4-(quinolin-3-ylacetyl)piperazine-1-carboxylate. [0643] Step 4: In an analogous manner to Example 261 step 4, tert-butyl 4-H2-quinoline-3-yl)-2-0-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[(2-quinoline-3-yl)-2-(1-hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate. [0644] Step 5: In an analogous manner to Example 261 step 5, 1-(2-piperazin-1-yl-1-quinolin-3-ylethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-[(2-quinoline-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS m/z 340; HRMS: calcd forC21H29N3O + H, 340.23889; found (ESI, [M+HJ+), 340.2402. Example 263 1 -1 -[4-(Benzyloxy)-3-(trifluoromethyDphenyl1-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride -232- WO 2005/037279 PCT/US2004/033732 [0645] Step 1: A solution of 2-trifluoromethyl phenol (5.0 g, 30.86 mmol) and hexamethylenetetramine (8.64 g, 61.72 mmol) in trifluoracetic acid (50 mL) was heated at 65CC for 18 h. At the end of this time the solution was concentrated and diluted with a 2N aqueious solution of hydrochloric acid. The acid phase was extracted twice with ethyl acetate and the combined organic extract dried over magnesium sulfate and concentrated. The residue was subjected to chromatography via Biotage (FLASH 40 M, silica, 20% ethyl acetate/hexane) to yleld 2.1 g (36%) of 4-hydroxy-3-(trifluoromethyl]benzaldehyl)e. MS (ES) m/z 188.9; HRMS: calcd for C8H5[3O2, 190.0242; found (ESI, [M+H]+), 191.0324. [0646] Step 2: A solution of 4-hydroxy-3-(trifluoromethyl)benzaldehyde 0.5 g, 8.0 mmol), benzyl bromide 0.51 g, 8.8 mmol) and potassium carbonate 0.66 g, 12.0 mmol) in dimethyl formamide (20 mL) was stirred water 000 mL) and extracted 3 times with ethyl acetate. The ethyl acetate extracts were combined and washed 2 times with water and dried over magnesium sulfate. Concentration in vacuo ylelded 1.7 g of 4-benzyloxy-3-trifluoromethyl-benzaldehyl)e which was used as such in the next step. [0647] Step 3: In an analogous manner to Example 261 step 1, 1-benzyloxy-4-(2.2-dibromo-vinyl-2-trifluoromethyl-benzene was prepared from 4-benzyloxy-3-trifluoromethyl-benzaldehyde. [0648] Step 4: In an analogous manner to Example 261, Step 2, tert-butyl 4-([4-(Benzyloxy)-3-trifluoromethylphenyl1acetyl)piperazine-1-carboxylate was prepared 1-benzyloxy-4-(2,2-dibromo-vinyl)-2-trifluoromethyl-benzenc. -233- WO 2005/037279 PCT/US20O-I/033732 [0649] Step 5: In an analogous manner to Example 135 step 2, tert-butyl 4-f[4- (Benzyloxy)-3-(trifluoromethyl]phenvH(1-hydroxycyclohexyl)acotyl]piperazine-1- carboxylate was prepared from tert-butyl 4-{[4-(benzyloxy)-3- trifluoromethylphenyl]acetyl}piperazine-1-carboxylate. MS (ESI) m/z 577; HRMS: calcd forC31H39[3N205, 576.2811; found (ESI, [M+H]+), 577.2901. [0650] Step 6: In an analogous manner to Example 135 step 3, tert-butyl 4-[2-[4-(Benzyloxy)-3-(trifluoromethyl)phenyl]-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[[4-(benzyloxy)-3-(trifluoromethyl)phenyl](1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ES) m/z 563.1; HRMS: calcd for C31H41[3N2O4, 562.3018; found (ESI, [M+HJ+), 563.3096. [0651] Step 7: In an analogous manner to Example 135 step 4, 1 -1 -[4-(Benzyloxy)-3- (trifluoromethyl)phenyn-2-piperazin-1-ylethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-[4-(benzyloxy)-3-(trifluoromethyl)phenyl]-2-0 - hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 463.0; HRMS: calcd for C26H33[3N2O2 + H, 463.25724; found (ESI. [M+H]+). 463.2554. Example 264 1-[1-[4-(Benzyloxy)-3-(trifluoromethyl)phenyl]-2-(4-methylpiperazin-1- yl)ethyncyclohexanol dihydrochloride [0652] In an analogous manner to Example 24, 1 -[1 -[4-(benzyloxy)-3- (trifluoromethyl]phenyl1-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-[4-(benzyloxy)-3-(trifluoromethyl)phenyl]-2-0- -234- WO 2005/037279 PCT/US2004/OJJ7J2 hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 477.1; HRMS: calcd for C2'7H35[3N2O2 + H, 477.27289; found (ESI, [M+H]+), 477.2711. Example 265 1-fi-[4-(Benzyloxy)-3-bromophenyl]-2-(4-methylpiperazin-1-yl)ethylicyclohexanol dihydrochloride [0653] Step 1: In an analogous manner to Example 263 step 2, 4-benzyloxy-3-bromo-benzaldehyde was prepared from 3-bromo-4-hydroxy-benzaldehyde. [0654] Step 2: In an analogous manner to Example 261 step 1, 1-benzyloxy-4-(2,2-dibromo-vinvQ-2-bromo-benzene was prepared from 4-benzyloxy-3-bromo-benzaldehyde. [0655] Step 3: In an analogous manner to Example 261 step 2, tert-butyl 4-([4-(Benzyloxy)-3-bromophenyl]acetyl)piperazine-1-carboxylate was prepared from 1-benzyloxy-4-(2,2-dibromo-vinyl)-2-bromo-benzene. MS (ES) m/z 432.9; HRMS: calcd for C24H29BrN2O4, 488.1311; found (ESI, [M+HJ+), 489.1394. [0656] Step 4: In an analogous manner to Example 135 step 2, tert-butyl 4-f[4-(Benzyloxy)-3-bromophenyl](1-hydroxycyclohexyl)acetvHpiperazine-1-carboxylate was prepared from , tert-butyl 4-{[4-(benzyloxy)-3-bromophenyl]acetyl}piperazine-1-carboxylate. MS (ES) m/z 587.0; HRMS: calcd for C30H39BrN2O5, 586.2042; found (ESI, [M+H]+), 587.2139. -235- WO 2005/037279 PCT/US2004/033732 [0657] Step 5: In an analogous manner to Example 135 step 3, tert-butyl 4-f[4- (berr2yloxv)-3-bromophenylin-hydroxycyclohexyl)ethyl1piperazine-1-carboxylate was prepared from tert-butyl 4-[[4-(benzyloxy)-3-bromophenyl]0- hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. [0658] Step 6: In an analogous manner to Example 24, 1-[1-[4-(Benzyloxy)-3- bromophenyl]-2-(4-methylpiperazih-1-yl)ethvHcyclohexanol dihydrochloride was prepared from tert-butyl 4-[[4-(benzyloxy)-3-bromophenyl]0- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 487.0; HRMS: calcd for C26H35BrN2O2 + H, 487.19601; found (ESI, [M+H]+), 487.1978. Example 2GG 2-(benzyloxy)-5-[1 -(1-hydioxycyclohexyl)-2-piperazin-1 -ylethylibenzonitriie dihydrochloride [0659] Step 1: In an analogous manner to Example 160, step 1, tert-butyl 4-f[4- (Benzyloxy)-3-cvanophenyl1(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[[4-(benzyloxy)-3-bromophenyl]0- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (See Example 265, step5). [0660] Step 2: In an analogous manner to Example 135, step 4, 2-(Benzyloxy)-5-[1-0- hydroxycyclohexyl-2-piperazin-1-ylethvHbenzonitrile dihydrochloride was prepared from tert-butyl 4-[[4-(benzyloxy)-3-cyanophenyl](1-hydroxycyclohexyl)ethyl]piperazine-1- carboxylate. MS (ES) m/z 420.1; HRMS: calcd for C26H33N3O2 + H, 420.26510; found (ESI, [M+H]+), 420.263. -236- WO 2005/037279 PCT/US2004/033732 Example 267 2-(Benzyloxy)-5-f1-(1-hydroxycyclohexyl)-2-(4-methylpiDerazin-1- vQethylibenzonitrile dihydrochloride [0661] In an analogous manner to Example 24, 2-(benzyloxy)-5-[1 -0 - hydroxycyclohexyl)-2-(4-methylpiperazin-1-yl)ethyl1benzonitrile dihydrochloride was prepared from 2-(benzyloxy)-5-[1 -(1-hydroxycyclohexyl)-2-piperazin-1 - ylethyl]benzonitrile dihydrochloride (See Example 267). MS m/z 434; HRMS: calcd for C27H35N3O2 + H, 434.28075; found (ESI, [M+H]+), 434.2821. Example 268 1 -1 -[4-(Benzyloxy)-3-(trifluoromethoxy)phenyl]-2-piperazin-1 -ylethyl)cyclohexanol dihydrochloride [0662] Step 1: In an analogous manner to Example 263 step 1 4-hydroxy-3-(trifluoromethoxy)benzaldehyde. was prepared from 2-trifluoromethoxy phenol. MS (ES) m/z 204.9; HRMS: calcd for C8H5[3O3, 206.0191; found (ESI, (M+HJ+), 207.0279. [0663] Step 2:. In an analogous manner to Example 263 step 2, 4-Benzyloxy-3- trifluoromethoxy-benzaldehyde was prepared from 4-hydroxy-3- (trifluoromethoxy)benzaldehyde. -237- WO 2005/037279 PCT/l!S2nO4/n33732 [0664] Step 3: In an analogous manner to Example 261 step 1, 1-benzyloxy-4-(2,2-dibromo-viny|)-2-(trifluoromethoxy)-benzene was prepared from 4-benzyloxy-3-trifluoromethoxy-benzaldehyde. HRMS: calcd for C16H11Br2[3O2, 449.9078; found (El, M-k), 449.9079 [0665] Step 4: In an analogous manner to Example 261, Step 2, tert-butyl 4-{[4-(BenzyloxyV3-trifluoromethoxyphenyl]acetyl}piperazine-1-carboxylate was prepared 1-benzyloxy-4-(2,2-dibromo-vinyl)-2-(trifluoromethoxy)-benzene. [0666] Step 5: In an analogous manner to Example 135 step 2, tert-butyl 4-f[4- (Benzyloxy)-3-(trit'luoromethoxy)phenvri0-'nyl)roxvcyclo'nexyl*)acetyripiperazine-1- carboxylate was prepared from tsrt-buty! 4-{[4-(benzyloxy)-3- trifluoromethoxyphenyl]acetyl}piperazine-1-carboxylate. [0667] Step 6: In an analogous manner to Example 135 step 3, tert-butyl 4-[2-[4-(benzyloxy)-3-(trifluoromethoxy)phenyl1-2-(1-hydroxycyclohexyl)ethyl1piperazine-1-carboxylate was prepared from tert-butyl 4-[[4-(benzyloxy)-3-(trifluoromethoxy)phenyl](1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. [0668] Step 7: In an analogous manner to Example 135 step 4, 1 -1 -[4-(Benzyloxy)-3-(trifluoromethoxy)phenyn-2-piperazin-1-ylethy[)cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-[4-(benzyloxy)-3-(trifluoromethoxy)phenyl]-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 479.0; HRMS: calcd for C26H33[3N2O3 + H, 479.25215; found (ESI, (M+H]+), 479.2506. Example 269: HI-n-naphthyQ^-piperazin-i-ylethyncyclooctanol dihydrochloride -238- WO 2005/037279 PCT/US2004/033732 [0669] In an analogous manner to Example 1, step 1 tert-butyl 4-fd- hydroxycyclooctyld -naphthyDacetylipiperazine-i -carboxylate was prepared from (1-naphthyl)(1-hydroxycyclooctyl)acetic acid (Reference Example 1-ddd) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 481. [0670] In an analogous manner to Example 1, step 2 1-H-(1-naphthyl)-2-piperazin-1-ylethyllcyclooctanol dihydrochloride was prepared from tert-butyl 4-[(1-hydroxycyclooctyl)(1-naphthyl)acety!]piperazine-1-carboxylate. MS (ESI) m/z 367; HRMS: calcd for C24H34N2O + H, 367.27494; found (ESI, [M+H]+), 367.2732. Example 270: 1 -[2-(4-methylpiperazin-1 -yl)-1 -0 -naphthyl)ethyl]cyclooctanol dihydrochloride [0671] In an analogous manner to Example 24, 1 -[2-(4-methylpjperazin-1 -yl)-1 -d -naphthyl)ethylicyclooctanol dihydrochloride was prepared from i-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclooctanol dihydrochloride (See Example 269). MS (ESI) m/z 381; HRMS: calcd for C25H36N2O + H, 381.29059; found (ESI, [M+H]+), 381.2893. Example 271: 1-[1-(1-naphthyl-2-piperazin-1-ylethyncycloheptanol dihydrochloride -239- WO 2005/037279 PCT/l!S2004/033732 [0672] In an analogous manner to Example 1, step 1 tert-butyl 4-[0- hydroxycycloheptyl)(1-naphthyl)acetyllpiperazine-1-carboxylate was prepared from (1-naphthyl)(1-hydroxycycloheptyl)acetic acid (Reference Example 1-fff) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 467.4. [0673] In an analogous manner to Example 1, step 2 1 -[1 -(1 -naphthyl)-2-piperazin-1 -ylethyl]cycloheptanol dihydrochloride was prepared from tert-butyl 4-[(1-hydroxycycloheptyl)(1-naphthyl)acetyl]piperazine-1-carboxylate. MS (ES) m/z 353.3; HRMS: calcd for C23H32N2O + H, 353.25929; found (ESI, [M+H]+), 353.2609. Example 272: 1 -[2-(4-methylpiperazin-1 -yl)-1 -(1 -naphthyl)ethylicycloheptanol dihydrochloride [0674] In an analogous manner to Example 24, 1 -[2-(4-methylpiperazin-1 -yl)-1 -(1 -naphthylethylicycloheptanol dihydrochloride was prepared from 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cycloheptanol . dihydrochloride (see Example 271). MS (ES) m/z 367.3; HRMS: calcd for C24H34N2O + H, 367.27494; found (ESI, [M+H]+), 367.2733. Example 273: 4-(4-aminopiperidin-1 -yl)-3-(3-chlorophenyl)-2-methylbutan-2-ol dihydrochloride -240- WO 2005/037279 PCT/US2004/033732 [0675] In an analogous manner to Example 1, step 1 tert-butyl 0 -[2-(3-chlorophenyl)-3-hydroxy-3-methylbutanoyl]piperidin-4-yl)carbamate was prepared from 2-(3-chlorophenyl)-3-hydroxy-3-methylbutanoic acid (Reference Example 1-ggg) and 4-N-boc-aminopiperidine. MS (ESI) m/z 411.0. [0676] In an analogous manner to Example 1, step 2 4-(4-aminopiperidin-1-yl)-3-(3-chlorophenyl)-2-methylbutan-2-ol dihydrochloride was prepared from tert-butyl {1-[2-(3-chlorophenyl)-3-hydroxy-3-methylbutanoyl]piperidin-4-yl}carbamate. MS (ESI) m/z 297; HRMS: calcd for C16H25CIN2O + H, 297.17337; found (ESI, [M+H]+), 297.1734. Example 274: 3-(3-chlorophenylM-[4-(dimethylamino)piperidin-1 -yl]-2-methylbutan-2-ol dihydrochloride [0677] In an analogous manner to Example 24, 3-(3-chlorophenyl)-4-[4- (dimethylamino)piperidin-1-yl]-2-methylbutan-2-ol dihydrochloride was prepared from 4-(4-aminopiperidin-1 -yl)-3-(3-chlorophenyl)-2-methylbutan-2-ol dihydrochloride (See Example 273). MS (ESI) m/z 325; HRMS: calcd for C18H29CIN2O + H, 325.20467; found (ESI, [M+H]+)f 325.2063. Example 275: 3-(3-chlorophenyl)-2-methyl-4-piperazin-1-ylbutan-2-ol dihydrochloride -241- W'O 2005/037279 PCT/US2004/033732 [0678] In an analogous manner to Example 1, step 1, tert-butyl 4-[2-(3-chlorophenyQ-3-hydroxv-3-methylbutanoyl]piperazine-1-carboxylate was prepared from 2-(3-chlorophenyl)-3-hydroxy-3-methylbutanoic acid (Reference Example 1-ggg) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 397.0. [0679] In an analogous manner to Example 1, step 2, 3-(3-chlorophenyl)-2-methyl-4-piperazin-1 -ylbutan-2-ol dihydrochloride was prepared from 1 tert-butyl 4-[2-(3-chiorophenyl)-3-hydroxy-3-methylbutanoyl]piperazine-1-carboxylate. MS (ES) m/z 283.0; HRMS: calcd for C15H23CIN2O + H, 283.15772; found (ESI, [M+H]+), 283.1581. Example 276: 3-(3-chlorophenyl)-2-methyl-4-(4-methylpiperazin-1 -yl)butan-2-ol dihydrochloride [0680] In an analogous manner to Example 24, 3-(3-chlorophenyl)-2-methyl-4-(4-methylpiperazin-1-yl)butan-2-ol dihydrochloride was prepared from 3-(3-chlorophenyl)-2-methyl-4-piperazin-1-ylbutan-2-ol dihydrochloride (See Example 275). MS (ES) m/z 297.0; HRMS: calcd for C16H25CIN2O + H, 297.17337; found (ESI, [M+H]+), 297.1719. -242- WO 2005/037279 PCT/US2004/033732 Example 277: 1-M-(3-chlorophenyl)-2-piperazin-1-ylethyn-3 3 5,5-tetramethylcyclohexanol dihydrochloride [0681] In an analogous manner to Example 1, step 1, tert-butyl 4-[(3-chlorophenvQ(1-hydroxy-3,3.5,5-tetramethylcyclohexyl)acetynpiperazine-1-carboxylate was prepared from 3-chlorophenyl)(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetic acid (Reference Example 1-hhh) and tert-butyl 1-piperazinecarboxylate. [0682] In an analogous manner to Example 1, step 2, 1 -[1 -(3-chlorophenyl)-2-piperazin-1-ylethyl1-3.3.5,5-tetramethylcyclohexanol dihydrochloride was prepared from tert-butyl 4-[(3-chlorophenyl)(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetyl]piperazine-1-carboxylate. MS (ES) m/z 379.3; HRMS: calcd for C22H35CIN2O + H, 379.25161; found (ESI, [M+H]+), 379.2527. Example 278: 1 -(1 -(3-chlorophenyl)-2-(4-methylpiperazin-1 -yl)ethyl1-3.3,5.5-tetramethylcyclohexanol dihydrochloride [0683] In an analogous manner to Example 24, 1 -[1 -(3-chlorophenyl)-2-(4- methylpiperazin-1-yl)ethvH-3.3.5,5-tetramethylcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]-3,3,5,5- -243- WO 2005/037279 PCT/US2004/033732 tetramethylcyclohexanol dihydrochloride (See Example 277). MS (ESI) m/z 393; HRMS: c£!cd for C23H37CIN2O + H, 393.26727; found (ESI, [M+H]+), 393.2653. Example 279: 1-[1-(5-methoxy-1-benzothien-3-yl)-2-piperazin-1-ylethyncyclohexanol dihydrochloride [0684] In an analogous manner to Exampie 1, step 1, tert-butyl 4-f0- MYl)roxvcvc!ohexy!)(5-rr!Gthoxv-1-benzothien-3-yl]acet\'HpiperazJne-1-carboxylate was prepared from (1-hydroxy-cyclohexyl)-(5-methoxy-benzo[b]thiophen-3-yl)-acetic acid (Reference Example 1-iii) and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 489.0. [0685] In an analogous manner to Example 1, step 2, 1 -[1 -(5-methoxy-1 -benzothien-3-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared tert-butyl 4-[(1-hydroxycyclohexyl)(5-methoxy-1-benzothien-3-yl)acetyl]piperazine-1-carboxylate. MS (ES) m/z 375.1; HRMS: calcd for C21H30N2O2S + H, 375.21062; found (ESI, [M+H]+), 375.2117. Example 280: 1-[2-(4-aminopiperidin-1-yl)-1-(5-methoxy-1-benzothien-3-ylethylicyclohexanol dihydrochloride -244- WO 2005/037279 PCT/US2004/033732 [0686] In an analogous manner to Example 1, step 1, tert-butyl 4-[0- hycifoxvcyclohexyl](5-methoxy-i-benzothien-3-yl]acetyl]pioeridine-4-Yl carbamate was prepared from (1-hydroxy-cyclohexyl)-(5-methoxy-benzo[b]thiophen-3-yl)-acetic acid (Reference Example 1-iii) and 4-N-boc-aminopiperidine. [0687] In an analogous manner to Example 1, step 2, 1 -[2-(4-aminopiperidin-1 -yl)-1 -(5-methoxy-1-benzothien-3-yl)ethyllcyclohexanol dihydrochloride was prepared from , tert-butyl 4-[(1-hydroxycyclohexyl)(5-methoxy-1 -benzothien-3-yl)acetyl]piperidine-4-yl carbamate. MS (ES) m/z 389.0; HRMS: calcd for C22H32N2O2S + H, 389.22627; found (ESI, [M+H]+), 389.2262. Example 281: 1 -[1 -(4-bromothien-2-yl)-2-piperazin-1 -ylethyllcyclohexanol dihydrochloride [0688] Step 1: in an analogous manner to Example 261 step 1, 4-hromo-2-(2,2-dibromovinyl)thiophene was prepared from 4-bromo-2-thiophenecarboxaldehyde. [0689] Step 2: In an analogous manner to Example 261 step 2, tert-butyl 4-f(4-bromothien-2-yl]aceryllpiperazine-1-carboxylate was prepared from 4-bromo-2-(2.2-dibromovinyOthiophene. [0690] Step 3: In an analogous manner to Example 135 step 2, tert-butyl 4-[2-(4-Bromo-thiophen-2-yl)-2-0-hydroxy-cyclohexyl)-acetyl]-piperazine-1-carboxylate was prepared from tert-butyl 4-[(4-bromothien-2-yl)acetyl]piperazine-1-carboxylate. -245- WO 2005/037279 PCT/US2004/033732 [0691] Step 4: In an analogous manner to Example 135 step 3, 4-[2-(4-Bromo- thio-phen-2-yl]-2-(1-hydroxy-cyclohexyl]-ethyl]-piperazine-1-carboxylate was prepared from 4-[2-(4-Bromo-thiophen-2-yl)-2-(1-hydroxy-cyclohexyl)-acetyl]-piperazine-1 - carboxylate. [0692] Step 5: In an analogous manner to Example 135 step 4, 1-[1-(4-bromothien-2-yl)-2-piperazin-1 -ylethyllcyclohexanol dihydrochloride was prepared from 4-[2-(4-Bromo-thiophen-2-yl)-2-(1-hydroxy-cyclohexyl)-ethyl]-piperazine-1 -carboxylate. MS (ES) m/z 372.9; HRMS: calcd for C16H25BrN2OS + H, 373.09492; found (ESI, [M+H]+), 373.0932. Example 232: 4-[2-(4-aminopiperidin-1 -yh-1 -O-chlorophenyl)ethyliheptan-4-ol dihydrochloride [0693] In an analogous manner to Example 1, step 1 tert-butyl 0 -[2-(3-chlorophenylV 3-hydroxv-3-propylhexanoyl1piperidin-4-yl}carbamate was prepared from 2-(3-chlorophenyl)-3-hydroxy-3-propylhexanoic acid (Reference Example 1-u) and 4-N-boc-aminopiperidine. MS (ESI) m/z 411.0. [0694] In an analogous manner to Example 1, step 2 4-[2-(4-aminopiperidin-1 -yl)-1 -(3-chlorophenyl)ethyl]heptan-4-ol dihydrochloride was prepared from tert-butyl {1-[2-(3-chlorophenyl)-3-hydroxy-3-methylbutanoyl]piperidin-4-yl}carbamate. MS (ES) m/z 353.3; HRMS: calcd for C20H33CIN2O + H, 353.23597; found (ESI, [M+H]+), 353.237. -246- WO 2005/037279 PCT/US2004/033732 Example 283: 1-(2-(4-methylpiperazin-1-Yl)-1-[4-(trifluoromethoxy')phenyl)ethyl) cyclohexanol dihydrochloride [0695] In an analogous manner to Example 1, step 1, 1-methyl -4-(0- hydroxycyclohexyl) [4-trifluoromethoxy)phenyl1acetyl)piperazine was prepared from (1-hydroxycyclohexyl) [4-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-g) and 1-methylpiperazine. MS(ESI) m/z 401 ([M+H]*) [0696] In an analogous manner Example 1, step 2 1 -(2-(4-methylpiperazin-1 -yl)-1 44-(trifluoromethoxy)phenyl]ethyl] cyclohexanol dihydrochloride was prepared from 1-methyl —4-{(1-hydroxycyclohexyl) [4-trifluoromethoxy)phenyl]acetyl}piperazine. MS(ESI) m/z 387 ([M+H]+) Example 284: 1-(2-0.4'- biDiperidin-1'-yl)-1-r4-(triflluoromethoxy)phenyl1ethyl) cyclohexanol dihydrochloride [0697] In an analogous manner to Example 1, step 1, 1 -(2-(4-piperidin-1 -ylpiperidin-1 -yl)-1-[4-(trifluoromethoxy)phenyl]-2-oxoethyl)cyclohexanol was prepared from (1-hydroxycyclohexyl) [4-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-g) and 4-piperidinopiperidine. MS(ESI) m/z 469 ([M+H]+) -247- WO 2005/037279 PCT/US2004/033732 [069'8] In an analogous manner Example 1, step 2 1-(2-0,4'- bipiperidin-1'-yl)-1-[4-(triflluoromethoxy)phenyliethyl) cyclohexanol dihydrochloride was prepared from 1-{2-(4-piperidin-1 -ylpiperidin-1 -yl)-1 -[4-(trifluoromethoxy)phenyl]-2-oxoethyl}cyclohexanol. MS(ESI) m/z 455 ([M+H]*). Anal Calcd for C25H37[3N2O22HCI 0.1 H2O: C.56.92; H,7.45: N.5.31. Found: C, 56.39; H.7.64; N.5.28 Example 285: 1 -(2-[4-0.3-benzodioxol-5-ylmethyl)piperazin-1 -yl]-1 -[4-(trifluoromethoxy)phenyl]ethyl) cyclohexanol dihydrochloride [0699] In an analogous manner to Example 1, step 1 1 -(2-[4-0.3-benzodioxol-5- ylmethyl)piperazin-1-yl]-1-[4-trifluoromethoxy)phenyl1-2-oxoethyl)cyclohexanol was prepared was prepared from (1-hydroxycyclohexyl) [4-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-g) and 1-piperonylpiperazine. MS(ESI) m/z 521 ([M+H]+) -248- WO 2005/0J7279 PCT/US2004/033732 [0700] In an analogous manner Example 1, step 2 1 -(2-[4-0.3-benzoioxol-5-ylmethyl)piperazin-i-yli-1 -[4-(trifluoromcthoxy)phenyl1ethyl) cyclohexanol ciihydrochloride was prepared from 1-{2-[4-0,3-benzodixol-5-ylmethyl)piperazin-1-yl]-1-[4-trifluoromethoxy)phenyl]-2-oxoethyl}cyclohexanol. MS(ESI) m/z 507 ([M+H]+). Anal Calcd for C27H33[3N2O42HCI 0.25H2O: C.55.53; H.6.13: N.4.80. Found: C, 55.29; H..6.14; N.4.74. Example 286: 1 -(2-[4-(cyclohexylmethvQpiperazin-1 -yl]-1 -[4-(trifluoromethoxy) phenyliefhyljcyclohexanol dihydrochloride [0701] In an analogous manner to Example 1, step 1 1-{2-[4- (cyclohexylmethyl)piperazin-i -yl]-1 -[4-(trifluoromethoxy)phenyl] 2-oxoethyl)cyclohexanol was prepared from (1-hydroxycyclohexyl) [4-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-g) and 1-cyclohexylmethyl)piperazine. MS(ESI) m/z 483 ([M+H]4) -249- WO 2005/037279 PCT/l'S2OO4/O337J2 [0702] In an analogous manner Example 1, step 2 1-(2-[4-(cvc')0hexylmethyl]Diperazin-1-yl]-1-[4-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from 1-{2-[4-(cyclohexylmethyl)piperazin-1-yl]-1-[4-(trifluoromethoxy)phenyl] 2-oxoethyl}cyclohexanol. MS(ESI) m/z 469 ([M+H]+). Anal Calcd for C26H39[3N2O22HCI: C.57.67; H.7.63: N.5.17. Found: C, 57.23; H..7.64; N.4.86 Example 287: 1 -(2-(4-ethylpiperazin-1 -yQ-1 -[4-(trifluoromethoxy)phenyl]ethyl) cyclohexanol dihydrochloride. [0703] In an analogous manner to Example 1, step 1 1-(2-(4-ethylpiperazin-1-yl)-1-[4-(trifluoromethoxy)phenyl]-2-oxoethyl)cyclohexanol was prepared from (1-hydroxycyclohexyl) [4-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-g) and 1-ethylpiperazine. MS(ESI) m/z 415 ([M+H]+ -250- WO 2005/037279 PCT/US200-I/03J7J2 [0704] In an analogous manner to Example 1, step 2 1 -(2-(4-ethylpiperazin-1 -yl)-1 -[4-(trif!uoromethoxy)phenyl]ethyl]cyclohexanol dihydrochloride was prepared from 1-{2-(4-ethylpiperazin-1 -yl)-1 -[4-(trifluoromethoxy)phenyl]-2-oxoethyl}cyclohexanol. MS(ESI) m/z 401 ([M+H]+). Anal Calcd for C21H3i[3N2O22HCI 0.25H2O: C.52.78; H.7.06: N.5.86. Found: C, 52.48; H..6.93; N.5.81. Example 288: 1-(2-fcis-3,5-dimethylpiperazin-1-yl1-1-[4(trifluoromethoxy)phenyl] ethyl} cyclohexanol dihydrochloride -251- WO 2005/037279 PCT7US 2004/033732 [0706] In an analogous manner to Example 1, step 2 1 -(2-fcis-3,5-dimethylpiperazin-1 -yll-1-[4'-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride was prepared from 1 -{2-[cis-3,5-dimethylpiperazin-1 -yl]-1 -[4-(irifluoromethoxy)phenyl]-2-oxoethyl}cyclohexanol MS(ESI) m/z 401 ([M+H]*). Anal Calcd for C21H31[3N2O22HCI 0.33H2O: C.52.62; H.7.08: N.5.84. Found: C, 52.69; H..6.97; N.5.61. Example 289: 1 -M -(2'-fluoro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0707] In an analogous manner to Example 135, step 3, fert-butyl 4-[2-(2'-fluoro-1.1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (Example 163, step 2) using 2-fluorophenylboronic acid. MS (ESI) m/z483 ([M+H]+); HRMS: calcd for C29H39FN2O3 + H, 483.3023; found (ESI, [M+H]+), 483.3006. -252- WO 2005/037279 PCT/US2004/033732 [0708] In an analogous manner to Example 135, step 4, 1 -[1 -(2'-fluoro-i ,1 '-hiphenyl-4-•yl)-2-piperazin-1 -ylethyllcyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(2'-fluoro-1,1 '-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 383 ([M+H]+); HRMS: calcd for C24H3i FN2O + H, 383.2499; found (ESI, [M+H]+), 383.2499. Example 290: 4'-[1-(1-hydroxycyclohexyl)-2-piperazin-1-ylethvri-1.1'-biphenyl-2- carbonitrile dihydrochloride [0709] In an analogous manner to Example 135, step 3, fert-butyl 4-[2-(2'-cyano-1.1 '-biphenvM-yl]^-d-hydroxvcyclohexyl)ethylipiperazine-i-carboxylate was prepared from .'ert-buiy! 4-{2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carbcxylate (Example 163, step 2) using 2-cyanophenylboronic acid. MS (ESI) m/z 490 ([M+H]+). [0710] In an analogous manner to Example 135, step 4, 4'-[1-0-hydroxycyclohexyl)-2-piperazin-1-ylethyl]-1.1'-biphenyl-2-carbonitrile dihydrochloride was prepared from tert-butyl 4-[2-(2'-cyano-1,1 '-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 390 ([M+H]+); HRMS: calcd for C25H31N3O + H, 390.2545; found (ESI, [M+H]+), 390.2532. Example 291: 1 -M -(2'.5'-dichloro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride -253- WO 2005/037279 PCT/t'S2004/033732 [0711] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(2'.5'-dichloro-1,1'-biphenyl-4-yl]-2-0-hydroxycyclohexyl)ethyl1piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (Example 163, step 2) using 2,5-diclorophenylboronic acid. MS (ESI) m/z 533 ([M+H]+); HRMS: calcd for C29H38CI2N2O3 + H, 533.2338; found (ESI, [M+H]+), 533.2332. [0712] In an analogous manner to Example 135, step 4, 1-[1-(2'.5'-dichloro-1.1'-biphenyl-4-yl-2-piperazin-1-ylethyl1cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(2',5'-dichloro-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. HRMS: calcd for C24H30CI2N2O + H, 433.1813; found (ESI, [M+H]+), 433.1806. Example 292: 1 -1 -[4-(BenzyloxyV3-chlorophenyl]-2-piperazin-1 -ylethyPcyclohexanol dihydrochloride -254- WO 2005/037279 PCT/US2004/033732 [4-(benzyloxy)-3-chlorophenyl](i-hydroxycyclohexyl)acetic acid (reference Example 1eee) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z543 ([M+H]4). [0714] In an analogous manner to Example 135, step 2, tert-butyl 4-[2-(4-Benzyloxy-3-chlorophenyl)-2-(1-hydroxycyclohexyl)ethyl1piperazine-1-carboxylate was prepared from tert-butyl 4-[[4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 529/531 ((M+H]+)- [0715] In an analogous manner to Example 135, step 4, 1 -1 -[4-(Benzyloxy)-3-chlorophenyl]-2-piperazin-1-ylethyl|cyclohexanol dihydrochloride was prepared from fert-butyl 4-[2-(4-benzyloxy-3-chlorophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 429 ([M+H]+); HRMS: calcd for C25H33CIN2O2 + H, 429.2309; found (ESI, [M+H]'). 429.2318. Example 293: 1-[1-[4-(benzyloxy)-3-chlorophenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride [0716] In an analogous manner to Example 24, 1 -[1 -[4-(Benzyloxy)-3-chlorophenyl1-2-(4-methylpiperazin-1 -yl)ethylicyclohexanol dihydrochloride was prepared from 1-{1-[4-(benzyloxy)-3-chlorophenyl]-2-piperazin-1-ylethyl}cyclohexanol (Example 292). MS (ESI) m/z 443 ([M+H]+); HRMS: calcd for C26H35CIN2O2 + H, 443.2465; found (ESI, [M+H]+), 443.2459. -255- WO 2005/037279 PCT/US2OO4/O33732 Example 294: 1-M-(3'-chloro-1,1'-biphenyl-4-yl]-2-(4-methylpiperazin-1-Yl)ethyl1cyclobutanol dihydrochloride [0717] In an analogous manner to Example 24, 1 -[1 -(3'-chloro-1.1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyllcyclobutanol dihydrochloride was prepared from 1-[1-(3'-ch!oro-"S,V-bSphcny!-4-yl)-2-pSpera2in-1-y!ethy!]cyc!obu!ano! (Example 18?). MS (ESI) m/z 385 ([M+H]+): HRMS: calcd for C23H29CIN2O + H, 385.20467; found (ESI, [M+H]+), 385.2054. Example 295: 1-(2-(4-methylpiperazin-1-yl]-1-[3'-(trifluoromethoxy)-1J'-biphenyl-4- yllethyllcyclobutanol dihydrochloride [0718] In an analogous manner to Example 24, 1-(2-(4-methylpiperazin-1-yl-1-[3'-(trifluoromethoxy)-i .1'-biphenyl-4-yl1ethyl)cyclobutanol dihydrochloride was prepared from 1-{2-piperazin-1 -yl-1 -[3"-(trifluoromethoxy)-1,1 '-biphenyl-4-yl]ethyl}cyclobutanol (Example 183). MS (ESI) m/z 435 ([M+H]+); HRMS: calcd for C24H29[3N2O2 + H, 435.2259; found (ESI, [M+H]+), 435.2256. -256- WO 2005/OJ7279 PCT/IJS2004/033732 Example 296: 1-[1-(3\4'-dichloro-1.1'-biphenv1-4-yl)-2-(4-methy|piperazin-1-yl]ethyllcyclobutanol dihydrochloride [0719] In an analogous manner to Example 24, 1-M-(3',4'-dichloro-1.1'-biphenyl-4-yl-2-(4-methylpiperazin-1 -yl)ethyl]cyclobutanol dihydrochloride was prepared from 1-[1-(3',4'-dichloro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclobutanol (Example 184). MS (ES!) m/z 419 ([M+H]*); HRMS: calnd for C23H2eCI2N2O + H. 419.1657; found (ESI, [M+H]+), 419.1667. Example 297: 1-[1-(3'.5'-dichloro-1.1'-biphenyl-4-yl-2-(4-methylpiperazin-1-yl]ethyl]cyclobutanol dihydrochloride [0720] In an analogous manner to Example 24, HH3',5'-dichloro-1,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl]ethylicyclobutanol dihydrochloride was prepared from 1-[1-(3',5r-dichloro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclobutanol (Example 185). MS (ESI) m/z 419 ([M+H]+); HRMS: calcd for C23H28Cl2N2O + H, 419.1657; found (ESI, [M+H]+), 419.1660. -257- WO 2005/037279 PCT/US200-I/033732 Example 298: 1-ri-(3-ethyl]ylphenyO-2-piperazin-1-ylethyl1cyclohexanol dihydrochloride [0721] In an analogous manner to Example 162, step 1, tert-butyl 4-(2-0- hydroxycyclohexyl)-2-(3-f(trimethylsilyl]ethyl]yllphenyl]ethyl)piperazine-1-carboxylate was prepared from fert-butyl 4-[2-(3-bromophenyl)-2-0- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (Example 135, step 2) using (trimethylsilylethynyl)tributyltin. MS (ESI) m/z 485 ([M+H]+); HRMS: calcd for C28H44N2O3Si + H, 485.3200; found (ESI, [M+H]+), 485.3202. [0722] To a solution of tert-butyl 4-(2-(1-hydroxycyclohexyl)-2-{3- [(trimethylsilyl)ethynyl]phenyl}ethyl)piperazine-1-carboxylate 004 mg, 0.215 mmol) in methanol (3 mL) was added potassium carbonate (300 mg, 2.17 mmol) and the mixture was stirred for 30 min at room temperature. The reaction mixture was quenched with aqueous ammonium chloride (5 mL) and extracted with ethyl acetate. The organic layer was washed with water, brine, dried (sodium sulfate), filtered and concentrated to give a crude oil, which was purified via silica gel flash chromatography (gradient from 10% ethyl acetate/hexane to 30% ethyl acetate/hexane) to yleld 70 mg (80%) tert-butyl 4-[2-(3-ethyl]ylphenyl)-2-(1-hydroxycyclohexyl)ethvripiperazine-1-carboxylate as a white solid. MS (ESI) m/z 413 ([M+H]+); HRMS: calcd for C25H36N2O3 + H, 413.2804; found (ESI, [M+H]+), 413.2809. [0723] In an analogous manner to Example 135, step 4, 1 -\ 1 -(3-ethyl]ylphenvQ-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3-ethynylphenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z -258- WO 2005/037279 PCT7US2004/033732 313 ([M+H]+); HRMS: calcd for C2oH2eN20 + H, 313.2280; found (ESl', [M+H]+), 313-2280. Example 299: 1 -[1 -(3-ethynylphenyl]-2-(4-methylpiperazin-1 -yl)ethyl1cyclohexanol dihydrochloride [0724] In an analogous manner to Example 24, 1 -f1 -(3-ethyl]ylphenyl)-2-(4- methylpiperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from 1-[1-(3-ethynylphenyl)-2-piperazin-1-ylethyl]cyclohexanol (Example 298). MS (ESI) m/z 327 ([M+H]+); HRMS: calcd for C21H3oN20 + H, 327.2436; found (ESI, [M+Hf), 327.2425. Example 300: 1 -[2-piperaz'm-1 -yl-1 -(3-proo-1 -ynylphenyl)e*hy!jcyc!ohexariOl dihydrochloride [0725] In an analogous manner to Example 162, step 1, tert-butyl 4-[2-0- hydroxycyclohexyl)-2-(3-prop-1-yl]ylphenyl)ethyl]piperazine-1-carboxylate was prepared from y -butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 - -259- WO 2005/OJ7279 PCT/IJS2004/033732 carboxylate (Example 135, step 2) using (i-propynyl)tributyltin. MS (ESI) m/z 427 ([M+K)]+); HRMS: calcd for C26H36N2O3 + H, 427.2961; found (ESI, [M+H]*), 427.2967. [0726] In an analogous manner to Example 135, stop 4, 1 -[2-piperazin-1 -yl-1 -(3-prop-1 -ynylphenyl)ethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(1-hydroxycyclohexyl)-2-(3-prop-1 -ynylphenyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 327 ([M+H]+); HRMS: calcd for C21H30N2O + H, 327.2436; found (ESI, [M+H]+), 327.2421. Example 301: 1-[2-(4-methylpiperazin-1-yl)-1-(3-prop-1-yl]ylphenyl)ethyl1cyclohexanol dihydrochloride [0727] In an analogous manner to Example 24, 1 -[2-(4-methylpiperazin-1 -yl)-1 -(3-prop-1 -yl]ylphenyl)ethyllcyclohexanol dihydrochloride was prepared from 1-[2-piperazin-1-yl-1-(3-prop-1-ynylphenyl)ethyl]cyclohexanol (Example 300). HRMS: calcd for C22H32N2O + H, 341.2593; found (ESI, [M+H]*), 341.2585. -260- WO 2005/037279 PCT/US2004/033732 Example 302: 1 -(2-(4-benzyl-1 ^-riiazepan-i-vh-1 -[4(trifluoromethoxy')phenyl]ethyl)cyclohexanol dihydrochloride [0728] In an analogous manner to Example 1, step 1 1 -(2-(4-benzyl-1,4-diazepan-1 -yl)-1 -[4-(trifluoromethoxy)phenyl]-2-oxoethyl)cyclohexanol was prepared from (1-hydroxycyclohexyl) [4-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-g) and 1-benzyl-homopiperazine. MS(ESI) m/z 491 ([M+H]+ [0729] In an analogous manner to Example 1, step 2 1 -(2-(4-benzyl-1.4-diazepan-1 -yl)-1-[4-(trifluoromethoxy)phenyl]ethyl)cyclohexanol dihydrochloride was prepared from 1 -{2-(4-benzyl-1,4-diazepan-1 -yl)-1 -[4-(trifluoromethoxy)phenyl]-2-oxoethyl}cyclohexanol. MS(ESI) m/z 477 ([M+HD- Anal Calcd for C27H35[3N2O22HCI 1H2O: C.57.14; H.6.93: N.4.94. Found: C, 57.02; H..7.44; N.4.98 Example 303: 1 -(2-(4-aminopiperidin-1 -yl>-1 -[4-(trifluoromethoxy)phenyl1ethyl) cyclohexanol dihydrochloride -261- WO 2005/037279 PCT/US2OO4/03J732 [0730] In an analogous manner to Example 1, step 1 tert-butyl 0- ?0-hVv1roxycyclohexyl)[4-(tvrifluoromethoxy)phenyl1acetyllpiperidin-4-yl)carbannate was prepared from (1-hydroxycyclohexyl) [4-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-g) and 4-N-BOC-aminopiperidine. MS(ESI) m/z 501([M+H]+) [0731] In an analogous manner to Example 1, step 2 1-(2-(4-aminopiperidin-1-yl)-1-[4-(trifluoromethoxy)Dhenyl]ethyl) cyclohexanol dihydrochloride was prepared from 1 tert-butyl 0- {(1-hydroxycycIohexyl)[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)carbamate. MS(ESI) m/z 387 ([M+H]+). Anal Calcd for C20H29[3N2O22HCI: C.52.29; H.6.80: N.6.10. Found: C, 52.22; H, 6.98; N.5.98 Example 304: 1-(2-pip6razin-1-y!-1-[4-(trif!uGrorncthoxv^phenv!1ethv!)cvc!obutano! dihydrochloride [0732] In an analogous manner to Example 1, step 1 tert-butyl 4-U1-hydroxycyclobutyl)[4-(trifluoromethoxy)phenyl]acetyl)piperazine-carboxylate was prepared from 0-hydoxycyclobutyl)[4-trifluoromethoxy)phenyl] acetic acid (Reference Example 1-aaa) and tert-butyl 1-piperazincarboxylate. MS(ESI) m/z 459 ([M+H]*). -262: WO 2005/037279 PCT/US2004/033732 [0733] In an analogous manner to Example 1, step 2 1-(2-piperazin-1-yl-1-[4-.(trif]uoromethoxy)phenyl]ethyl)cyclobutanol dihydrochioride was prepared from 1 tert-butyl4-{(1-hydroxycyclobutyl)[4-(trifluoromethoxy)phenyl]acetyl}piperazine-carboxylate. MS(ESI) m/z 345 ([M+H]+). Anal Calcd for C17H23[3N2O22HCI 0.5 H2O : C.47.90; H.6.15: N.6.57. Found: C, 47.81; H, 5.92; N.6.43 Example 305: 1-(2-(4-aminopiperidin-1-yl)-H4-(trifluoromethoxy) phenyl]ethyl) cyclobutanol dihydrochloride [0734] In an analogous manner to Example 1, step 1 tert-butyl 0-10-hyl)oxvcyclobutyl)[4-(trifluoromethoxy)phenyl]acetyl|piperidin-4-yl)carbamate was prepared from 0-hydoxycyc!obutyl)[4-trif!uoromethoxy)phenyl] acetic acid (Reference Example 1-aaa) and 4-N-BOC-aminopiperidine. MS(ESI) m/z 473 ([M+H]+). -263- WO 2005/037279 PCT/US200-I/033732 [0735] In an analogous manner to Example 1, step 2 1 -{2-(4-aminopipcridin-1 -yQ-1 -[4-(trifh.oromethoxy) phenyliethyDcyclobutanol dihydrochloride was prepared from tert-butyl 0 -{(1-hydoxycydobutyl)[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)carbamate. MS(ESI) m/z 359 ([M+H]+). Example 306: 1 -(2-(4-methyl-1.4-diazepan-1 -yl)-1 -[4-(trifluoromethoxy) phenyliethylcyclobutanol dihydrochloride [0736] In an analogous manner to Example 1, step 1 1 -{2-(4-methyl-1.4-diazepan-1 -yl-1 -[4-(trifluoromethoxy) phenyl]-2-oxo-ethyl)cyclobutanol was prepared from 0-hydoxycyclobutyl)[4-trifluoromethoxy)phenyl] acetic acid (Reference Example 1-aaa) and 1-methylhomopiperazine. MS(ESI) m/z 387 ([M+H]+). -264- WO 2005/037279 PCT/US2004/03J732 [0737] In an analogous manner to Example 1, stop 2 1-{2-(4-methyl-i.4-diazepan-1- yl)-t-[4-(trifluoromethoxy) phenyliethyDcyclobutanol dihydrochloride was prepared from 1-{2-(4-methyl-1,4-diazepan-1-yl)-i-[4-(trifluorornethoxy) phenyl]-2-oxo- ethyl)cyclobutanol. MS(ESI) m/z 373 ([M+H]+). Anal Calcd for C1oH27[3N2022HCI 0.60 H2O : C.50.03; H.6.67: N.6.10. Found: C, 49.88; H, 6.58; N.6-02. Example 307: 1-[1-(4-phenoxyl)henyl)-2-piperazin-1-ylethyl1cvcohexanol dihydrochloride [0738] In an analogous manner to Example 1, step 1 tert-butyl 4-((1-hydroxycyclohexyl)[4-(phenoxv)phenyl1acetyl)piperazine-carboxylate was prepared from 0-hydoxycyclohexyl)[4-phenoxyphenyl] acetic acid (Reference Example 1-bbb) and tert-butyl 1-piperazinecarboxylate. MS(ESI) m/z 495 ([M+H]+). -265- WO 2005/037279 PCT/US2004/03J732 [0739] In an analogous manner to Example 1, step 2 1-[1-(4-phenoxyl)henyl1-2-piperc/2in-1-ylethyl]cvcohexanol dihydrochloride was prepared from fert-butyl 4-{(1-hydroxycyclohexyl)[4-(phenoxy)phenyl]acetyl}piperazine-carboxylate. MS(ESI) m/z 381 ([M+H]+). Anal Calcd for C24H32N2O22HCI 1H2O : C.61.14; H.7.89: N.5.94. Found: C, 60.96; H, 7.89; N.5.96. Example 308: 1 -[2-(4-methylpiperazin-1 -yl)-1 -(4-phenoxyphenyOethylcyclohexanol dihydrochloride [0740] In an analogous manner to Example 1, step 1 1 -[2-(4-methylpiperazin-1 -yl)-1 -(4-phenoxyphenyl)-2-oxoethv1cyclohexanol was prepared from 0-hydoxycyclohexyl)[4-phenoxyphenyl] acetic acid (Reference Example 1-bbb) and 1-methylpiperazine. MS(ESI) m/z 409 ([M+H]*)- -266- WO 2005/037279 PCT/US2004/033732 [0741 ] In an analogous manner to Example 1, step 2 H2-(4-methylpiperazin-1-yl)-1-(4£phenoxyphenyl)ethv1cyclohexanol dihydrochloride was prepared from 1-[2-(4-methylpiperazin-1 -yl)-1 -(4-phenoxyphenyl)-2-oxoethy]cyclohexanol. MS(ESI) m/z 395 ([M+H]+). Anal Calcd for C25H34N2O22HCI 0.9H2O : C.62.08; H.7.88: N.5.79. Found: C, 62.26; H, 8.11; N.5.70. Example 309: 1 -[2-[4-(cyclohexylmethvQpiperazin-1 -yl]-1 -(4-phenoxyl)henyl)ethyl] cyclohexanol dihydrochloride [0742] In an analogous manner to Example 1, step 1 1-i2-[4-(cyclohexylmethyl)piperazin-i -yl]-1 -(4-phenoxyl)henyl)-2-oxoethyl1 cyclohexanol was prepared from 0-hydoxycyclohexyl)[4-phenoxyphenyl] acetic acid (Reference Example 1-bbb) and 1-(cyclohexylmethyl)piperazine. MS(ESI) m/z 491 ([M+H]+). -267- WO 2005/037279 PCT/US2004/033732 [0743] In an analogous manner to Example 1, step 2 i-[2-[4-(cycloh-sxylmethyl)piperazin-1-Yl]-1-(4-nhenoxyl)henyl)ethyl1 cyclohexanol dihydrochloride was prepared from 1-[2-[4-(cyclohexylmethyl)piperazin-1-yl]-1-(4-phenoxyphenyl)-2-oxoethyl] cyclohexanol._ MS(ESI) m/z 477 ([M+H]+). Anal Calcd for C31H44N2O92HCI 1H2O : C.65.59; H.8.52: N.4.94. Found: C, 65.55; H, 8.79; N.4.90. Example 310: 1-(2-(4-aminopiperidin-1-yl)-1-(4-phenoxyl)henyl)ethyl]cyclohexanol dihydrochloride [0744] In an analogous manner to Example 1, step 1, tert-butyl 0-1(1-hydroxycyclohexyl)[4-(phenoxv)phenyl]acetyl)piperidin-4-yl)carbamate was prepared from 0-hydoxycyclohexyl)[4-phenoxyphenyl] acetic acid (Reference Example 1-bbb) and 4-N-BOC-aminopiperidine. MS(ESI) m/z 509 ([M+H]+). [0745] In an analogous manner to Example 1, step 2 1 -(2-(4-aminopiporidin-1 -yl)-1 -(4-phenoxyl)henyl)ethylicyclohexanol dihydrochloride was prepared from tert-butyl 0-{(1-hydroxycyclohexyl)[4-(phenoxy)phenyl]acetyl}piperidin-4-yl)carbamate. MS(ESI) m/z 395 ([M+H]+). Example 311: 1-[1-(3-phenoxyphenyl)-2-piperazin-1-ylethv]cyclohexanol dihydrochloride -268- WO 2005/037279 PCT/US2004/033732 [0746] In an analogous manner to Example 1, step 1 tert-butyl 4-((i-hydrQxycyclohexyl)[3-(phenoxv)phenyl]acetyl)piperazine-carboxylate was prepared from 0-hydoxycyclohexyl)[3-phenoxyphenyl] acetic acid (Reference Example 1-ccc) and tert-butyl 1-piperazincarboxylate. MS(ESI) m/z 495 ([M+H]+). [0747] In an analogous manner to Example 1, step 2 1 -[1 -(3-phenoxyphenyl)-2-piperazin-1 -ylethylicycohexanol dihydrochloride was prepared from 1 tert-butyl 4-{(1-hydroxycyclohexyl)[3-(phenoxy)phenyl]acetyl}piperazine-carboxylate. MS(ESI) m/z 381 ([M+H]+). Anal Calcd for C24H32N2O22HCI 1.8H2O : C.59.33; H.7.80: N.5.77. Found: C, 59.09; H, 7.7.15; N.5.48. Example 312: 1 -[2-(4-methylpiperazin-1 -yl)-1 -(4-phenoxyl)henyl)ethv]cyclohexanol dihydrochloride [0748] In an analogous manner to Example 1, step 1 1 -[2-(4-methylpiperazin-1 -yl-1 -(3-phenoxyphenyl)-2-oxoethy1cyclohexanol was prepared from 0-hydoxycyclohexyl)[3-phenoxyphenyl] acetic acid (Reference Example 1-ccc) and 1-methylpiperazine. MS(ESI) m/z 409 ([M+H]*). -269- WO 2005/037279 PCT/US2004/033732 [0749] In an analogous manner to Example 1, step 2 1-[2-(4-methylpiperazin-1-ylVi-(3-phenoxyl)hGnyl)ethylcyclohexanol dihydrochloride was prepared from 1 -[2-(4-methylpiperazin-1-yl)-1-(4-phenoxyphenyl)-2-oxoethy]cyclohexanol. MS(ESI) m/z 395 ([M+H]4). Anal Calcd for C25H34N2O22HCI 0.9H2O : C.62.08; H.7.88: N.5.79. Found: C, 62.26; H,8.11;N,5.70. Example 313:1 -[2-[4-(cyclohexylmethyl)piperazin-1 -yl]-1 -O-phenoxyphenyl)ethyl] cyclohexanol dihydrochloride [0750] In an analogous manner to Example 1, step 1 1-[2-[4-(cyclohexylmethyl)piperazin-1-yl]-1-(3-phenoxyphenyl]-2-oxoethyl1 cyclohexanol was prepared from 0-hydoxycyclohexyl)[3-phenoxyphenyl] acetic acid (Reference Example 1-ccc) and 1-(cyclohexylmethyl)piperazine. MS(ESI) m/z 491 ([M+H]+). [0751 ] In an analogous manner to Example 1, step 2 1-[2-[4-(cyclohexylmethyl)piperazin-i -yl]-1 -(3-phenoxyl)henyl)ethyl] cyclohexanol dihydrochloride was prepared from 1 1-[2-[4-(cyclohexylmethyl)piperazin-1-yl]-1-(3-phenoxyphenyl)-2-oxoethyl] cyclohexanol._MS(ESI) m/z 477 ([M+H]+). Example 314: 1-[2-0.4'- bipiperidin-1'-yl)-1-[3-(phenoxyphenyl)ethyl1cyclohexanol dihydrochloride -270- WO 2005/037279 PCT/LS2OO-I/033732 [0752] In an analogous manner to Example 1, step 1, 1-[2-0.4'- bipiperidin-1'-yl)-1-[3-(phenoxyl)henyl-2-oxoethylicyclohexanol was prepared from 0-hydoxycyclohexyl)[3-phenoxyphenyl] acetic acid (Reference Example 1-ccc) and 4-piperidinopiperidine MS(ESI) m/z 477 ([M+H]+) [0753] In an analogous manner Example 1, step 2 1 -[2-0,4'- bipiperidin-V-yQ-1 -[3-(phenoxyl)henyl)ethvHcyclohexanol dihydrochloride was prepared from 1-[2-0,4'-bipiperidin-1'-yl)-1-[3-(phenoxyphenyl)-2-oxoethyl]cyclohexanol MS(ESI) m/z 463 ([M+H]+). Anal Calcd for C3oH42N2022HCI 0.25H2O: C.66.72; H.8.31: N.5.18. Found: C, 66.96; H.8.87; N.4.32 Example 315: 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3-phenoxyl)henyl)ethyl1cyclohexanol dihydrochloride [0754] In an analogous manner to Example 1, step 1, y -butyl 0-((1-hydroxycyclohexyl)[3-(phenoxv)phenyl]acetyl)piperidin-4-yl)carbamate was prepared from 0-hydoxycyclohexyl)[3-phenoxyphenyl] acetic acid (Reference Example 1-ccc) and 4-N-BOC-aminopiperidine. MS(ESI) m/z 509 ([M+H]+). -271- NYL 2005/037279 PCT/US200-I/033732 [0755] In an analogous manner to Example 1, step 2 1_-(2-(4-aminopjperidin-1 -ylV-1 -(3-prenoxyphenylGthyl]cyclohexanol dihydrochloride was prepared from tert-butyl 0-{(1-hydroxycyclohexyl)[3-(phenoxy)phenyl]acotyl}piperidin-4-yl)carbamate. MS(ESI) m/z 395 ([M+H]+). Example 316: 1-[1-(3-phenoxyl)henyl)-2-(4-pvrrolidin-1-ylpiperidin-1-yl)ethylicyclohexanol dihydrochloride [0756] In an analogous manner to Example 1, step 1 1 -f1 -(3-phenoxyphenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)-2-oxoethyl]cyclohexanol was prepared from 0-hydoxycyclohexyl)[3-phenoxyphenyl] acetic acid (Reference Example 1-ccc) and 4-pyrrolidinylpiperidine. MS(ESI) m/z 463 ([M+H]+). [0757] in an analogous manner to Exampie 1, step 2 1 -11 -(3-phenoxyl)'nenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl]ethyl]cyclohexanol dihydrochloride was prepared from 1-[1-(3-phenoxyphenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)-2-oxoethyl]cyclohexanol. MS(ESI) m/z 449 ([M+H]+). Example 317: 1 -[2-[4-(dimethylamino)piperidin-1 -yl]-1 -(2-naphthyl)ethyl]cyclohexanol dihydrochloride -272- WO 2005/037279 PCT/i:S2004/033732 [0758] In an analogous manner to Example 36, 1-[P-[4-(dimethylamino)piperidin-1-yl]-1 -(2-naphthyQethyl]cyclohexanol dihydrochloride was prepared from 1-[2-(4-aminopiperidin-1-yl)-1-(2-naphthyl)ethyl]cyclohexanol (see Example 32). HRMS: calcd forC25H36N2O + H, 381.29059; found (ESI, [M+H]+), 381.2887. Example 318: 1-{1-(3-bromo-4-methoxyphenyl)-2-[4-(dimethylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride [0759] In an analogous manner to Example 36, 1 -0 -(3-bromo-4-methoxyphenyl)-2-[4- (dimethylamino)piperidin-1-yl]ethyl)cyclohexanol dihydrochloride was prepared from 1- [2-(4-aminopiperidin-1 -yl)-1 -(3-bromo-4-methoxyphenyl)ethyl]cyclohexanol (see Example 25). HRMS: calcd for C22H35BrN2O2 + H, 439.19601; found (ESI, [M+H]+), 439.1938. Example 319: 1-{1-(3-bromophenyl)-2-[4-(dimethylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride [0760] In an analogous manner to Example 36, 1 -0 -(3-bromophenyl)-2-[4- (dimethylarnino)piperidin-1-vHethyl)cyclohexanol dihydrochloride was prepared from 1-[2-(4-aminopiperidin-1-yl)-1-(3-bromophenyl)ethyl]cyclohexanol (see Example 18). HRMS: calcd for C2iH33BrN2O + H, 409.18545; found (ESI, [M+H]+). 409.1841. -273- wo ¦>o(\>n).^i-!<) rcT/L's:no4/0337j: (Sample 320: 1-{1-(3.4-dichlorophenyl)-2-[4-(dimethylamino)piperidin-1-yl]ethyl)cyclohexanol dihydrochloride [0761] In an analogous manner to Example 36, 1 -0 -O^-dichlorophenyl)^^-(dimethylamino)piperidin-1-yllethyl}cyclohexanol dihydrochloride was prepared from 1-[2-(4-aminopiperidin-1-yl)-1-(3,4-dichlorophenyl)ethyl]cyclohexanol (see Example 14). HRMS: caicd for C2iH32Ci2N2O + H, 399.19699; found (ESI. (M+H]+), 399.197. Example 321: 1-{2-[4-(dimethylamino)piperidin-1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride [0762] In an analogous manner to Example 36, 1-(2-[4-(dimethylamino)piperidin-1-yl]-1-[3-(trifluoromethyl)phenyl1ethyl)cyclohexanol dihydrochloride was prepared from 1-{2-(4-aminopiperidin-1 -yl)-1 -[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol (see Example 39). HRMS: calcd for C^HaaFs^O + H, 399.26232; found (ESI, [M+H]*). 399.2607. Example 322: 1-[2-(4-Methyl-1-piperazinyl)-1-[4-phenylmethoxy)phenyl]ethyl]cyclohexanol dihydrochloride -274- WO 2005/037279 PCT/US2004/033732 [0763] In an analogous manner to Example 24, 1-[2-(4-Methyl-1-piperazinyl)-1-[4-phenylmethoxy)phenyl1ethvHcyclohexanol dihydrochloride was prepared from 1-{1-[4-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol (see Example 27). MS (ESI) m/z 409; HRMS: calcd for C26H36N2O2 + H, 409.28550; found (ESI, [M+H]+), 409.2831. Example 323: 1 -(0 ffl-1 -[4-(BenzyloxyV3-chloroDhenyl]-2-piperazin-1 -ylethyl)cyclohexanol dihydrochloride [0764] Racemic y -butyl 4-[[4-(benzyloxy)-3-chlorophenyl]0- hydroxycyclohexyl)acetyl]piperazine-1-carboxylate (see Example 292, step 1) was dissolved in methanol at a concentration of approximately 50 mg/mL The resulting solution was injected onto the Supercritical Fluid Chromatography instrument with an injection yl]ume of 750 CL The baseline resolved enantiomers, using the conditions described below, were collected. The enantiomeric purity of each enantiomer was determined under the same Supercritical Fluid Chromatography conditions using a Chiralpak AD-H 5u, 250 mm x 4.6 mm ID column at 2.0 mL/min flow rate using Analytical Supercritical Fluid Chromatography (Berger Instruments, Inc. Newark, DE USA). -275- WO 2005/037279 PCT/US2OO4/0JJ732 SFC Instrument: Berger MultiGram PrepSFC (Berger Instruments, Inc. Newark, DE 19702. Column: Chiralcel OJ-H; 5u; 250mm L x 20mm ID (Chiral Technologies, Inc, Exton, PA, USA) Column temperature: 35°C SFC Modifier: 40% MeOH Flow rate: 60 mL/min Outlet Pressure: 100 bar Detector: UV at 220 nm tert-butyl 4-f(2S)-2-[4-(Benzyloxy)-3-chlorophenyl]-2-0- hydroxycyclohexyl)acetyliPiperazine-1-carboxylate was isolated at peak 1. MS (ES) m/z 543.1; HRMS: calcd for C30H39CIN2O5 + H, 543.26258; found (ESI, [M+H]+), 543.262 rerf-butyl 4-f(2ff)-2-[4-(Benzyloxy)-3-chlorophenyl]-2-0- hydroxycyclohexyl)acetyl]piperazine-1-carboxylate was isolated at peak 2. MS (ESI) m/z 543; HRMS: calcd for C3oH39CIN205 + H, 543.26258; found (ESI, [M+H]+), 543.263 [0765] In an analogous manner to Example 1, step 2 1 -(0 ff)-1 -[4-(benzyloxy)-3-chlorophenyl]-2-piperazin-1-ylethyl)cyclohoxanol dihydrochloride was prepared from tert-butyl 4-[(2S)-2-[4-(benzyloxy)-3-chlorophenyl]-2-0 - hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z429; HRMS: calcd for C25H33CIN2O2 + H, 429.23088; found (ESI, [M+H]+), 429.3206. CD = (-) @ 260-280 nm. Example 324: 1 -(05V1 -[4-(Benzyloxy)-3-chlorophenyl1-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride -276- WO 2005/037279 PCT/US2004/033732 [0766] In an analogous manner to Example 1, step 2 1 -(0 S)-1 -[4-(Benzyloxy)-3- chlorophenyl]-2-piperazin-1-ylethyl)cyclohexanol dihydrochloride was prepared from tert-butyl 4-[(2f?)-2-[4-(benzyloxy)-3-chlorophenyl]-2-0 - hydroxycyclohexyl)acetyl]piperazine-1-carboxylate (see Example 323). MS (ES) m/z 429.0; HRMS: calcd for C25H33CIN2O2 + H, 429.23088; found (ESI, (M+H]+), 429.2319. CD = (+) @ 260-280 nm. Example 325: 1-[0/?)-1-[4-(Benzyloxy)-3-chlorophenyl]-2-(4-methylpiperazin-1- yl)ethyncyclohexanol dihydrochloride [0767] In an analogous manner to Example 24 1-f0f?)-1-[4-(benzyloxy)-3- chlorophenyl1-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride was prepared from 1 -{0 f?)-1 -[4-(benzyloxy)-3-chlorophenyl]-2-piperazin-1 - ylethyljcyclohexanol (see Example 323). MS (ESI) m/z 443; HRMS: calcd for C26H35CIN2O2 + H, 443.24653; found (ESI, [M+H]+), 443.2474. CD = (-) @ 260-280 nm. Example 326:1-[1S)-1-[4-(Benzyloxy)-3-chlorophenyl]-2-(4-methylpiperazin-1- yl)ethyl]cyclohexanol dihydrochloride -277- WO 2005/037279 PCT/US20O4/033732 [0768J In an analogous manner to Example 24 1-f0S)-H4-(Benzyloxy)-3- ch!orophenyl1-2-(4-methylpiperazin-1-yl)fithyl]cyclohexanol dihydrochloride was prepared from 1-{0S)-i-[4-(benzyloxy)-3-chlorophenyl]-2-piperazin-1- ylethyl}cyclohexanol (see Example 324). MS (ES) m/z 443.1; HRMS: calcd for C26H35CIN2O2 + H, 443.24653; found (ESI, [M+H]+), 443.2473. CD = (+) @ 260-280 nm. Example 327: 2-[2-(4-aminopiperidin-1-yl)-1-(3-chlorophenyl)ethyl1decahydronaphthalen-2-ol dihydrochloride [0769] In an analogous manner to Example 1, step 1 re/1-butyl {1 -[(3-chiorophenyl'n'2-hydroxyl)ecahydronaphthalen-2-yl)acetyl1piperidin-4-yl)carbamate was prepared from (3-chlorophenyl)(2-hydroxydecahydronapthyl)acetic acid (Reference Example 1-cc) and 4-N-boc-aminopiperidine. MS (ES) m/z 505.3 [0770] In an analogous manner to Example 13, step 2 2-[2-(4-aminopiperidin-1 -yl)-1 - (3-chlorophenyl)ethyl]decahydronaphthalen-2-ol dihydrochloride was prepared from tert- butyl {1-[(3-chlorophenyl)(2-hydroxydecahydronaphthalen-2-yl)acetyl]piperidin-4- yljcarbamate. MS (ES) m/z 391.4; HRMS: calcd for C23H35CIN2O + H, 391.25161; found (ESI, [M+H]+), 391.2527 Example 328: 4-ethyl-1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl]ethyl]cyclohexanol dihydrochloride -278- WO 2005/037279 PCT/L'S20O4/0JJ732 [0771 ] In an analogous manner to Example 24 4-ethyl-1-[2-(4-methylpiperazin-1-yl)-1-0 -naphthynethyl]cyclohexanol dihydrochloride was prepared from 4-ethyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 91). MS (ESI) m/z 381; HRMS: calcd for CJSHW^O + H, 381.29059; found (ESI, [M+H]*), 381.2888 Example 329: 2-[1-(1-naphthyl)-2-piperazin-1-ylethyl]decahydronaphthalen-2-ol dihydrochloride [0772] In an analogous manner to Example 1, step 1 tert-butyl 4-f (2-hydroxyl)ecahydronaphthalen-2-yl)(1-naphthyl)acetylipiperazine-1-carboxylate was prepared from (3-chlorophenyl)(2-hydroxydecahydronapthyl)acetic acid (Reference Example 1-jjj) and fert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 507 [0773] In an analogous manner to Example 1, step 2 2-[1 -(1 -naphthyl)-2-piperazin-1 -ylethylidecahydronaphthalen-2-ol dihydrochloride was prepared from te/1-butyl 4-[(2-hwdroxudscahudronarvhtha!en-2-x/!^1 -narvhtnx/!^aceix/i"'r>irieraz!ne-1 -carboxwi2te. MS nvz 393; HRMS: calcd for C26H36N2O + H, 393.29059; found (ESI, [M+H]+), 393.2891 Example 330: 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3-chlorophenyl)ethyl]-4-methylcyclohexanol dihydrochloride -279- WO 2005/037279 PCT7US200-I/03.1732 [0774] In an analogous manner to Example 1, step 1 tert-butyl (i-[(3-chlorophenyl]d-hy