WO 2005/037809 PCT/US2004/033990 SUBSTITUTED ARYL CYCLOALKANOL DERIVATIVES AND METHODS OF THEIR USE 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. 60/510,943 filed October 14, 2003, 60/561,301 filed April 12, 2004, and 60/569,996 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 aryl cycloalkanoyl 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, nervous 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 nervous 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 thirty 1 WO 2005/037809 PCT/US2004/033990 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 nervousness, fatigue, irritability, insomnia, depression, memory loss, headache, anxiety, nervousness 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., 3rd Int'l Symposium on Recent Advances in Urological Cancer Diagnosis and Treatment-Proceedings, Paris, France: SCI: 3-7 (1992)). [0004] Hot flushes may be even more severe in women treated for breast cancer for several reasons: 1) many survivors 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, 419(1): 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 2 WO 2005/037809 PCT/US2004/033990 Physio ogy of Menopausal Hot Flashes: A Review," Can. J. Physiol. Pharmacol., 1987,65:1312-1324). [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 of the hypothalamus. The descending pathways from the hypothalamus via brainstem/spinal cord and the adrenals to the skin are involved in maintaining normal skin temperature. The action of NE and 5-HT reuptake inhibitors is known to impinge on both the CNS and peripheral nervous 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 involvement 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] 3 WO 2005/037809 PCT/US2004/033990 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 varying degree of success (Waldinger et al., Maturitas, 2000, 36(3): 165-168). [0010] It has been reported that a2adrenergic receptors play a role in thermoregulatory dysfunctions (Freedman et al., Fertility & Sterility, 2000, 74(1): 20-3). These receptors are located both pre- and post-synaptically and mediate an inhibitory role in the central and peripheral nervous system. There are four distinct subtypes of the adrenergic?? receptors, i.e., are ?2A. ?2B, ?2C and ?2D (Mackinnon et al., TIPS, 1994, 15: 119; French, Pharmacol. Ther., 1995, 68: 175). It has been reported that a non-select ?2-adrenoceptor antagonist, yohimbine, induces a flush and an ?2-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, 74(1): 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 necessaiy 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 aryl cycloalkanoyl 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, 4 WO 2005/037809 PCT/US2004/033990 gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous 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: or a pharmaceutical salt thereof; wherein: W is H or OR9; R1 is phenyl, naphthyl, heteroaryl, benzyloxy, phenoxy, naphthyloxy, phenylethoxy, phenoxyethoxy, naphthylmethoxy, naphthylethoxy, phenylcarbonylamino, phenylaminocarbonyl, trifluoromethoxy, nitrile, alkenyl, alkynyl, sulfonyl, sulfonamido, alkanoyl, alkoxycarbonyl, alkylaminocarbonyl, or amino; where said phenyl, naphthyl, heteroaryl, benzyloxy, phenoxy, naphthyloxy, phenylethoxy, phenoxyethoxy, naphthylmethoxy, naphthylethoxy, phenylcarbonylamino, and phenylaminocarbonyl are optionally substituted with one or more R2; R2 is H, or one or two substituents, the same or different selected from OH, alkyl, alkoxy, halo, trifluoromethyl, alkanoyloxy, methylenedioxy, trifluoromethoxy, nitrile, nitro, alkenyl, alkynyl, sulfonyl, or sulfonamido; 5 WO 2005/037809 PCT/US2004/033990 R5 is H, (C1-C6)alkyl, or trifluoromethyl; R6 and R7 are, independently, (C1-C6)alkyl or (C3-C6)cycloalkyl; or R6 and R' 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 R5 and R7 may be optionally substituted with R5 or OH; 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-C6)alkyl, hydroxy(C1-C6)alkyl, benzyl (optionally substituted with benzyloxy or phenyloxy), naphthylmethyl (optionally substituted with one or more R1), phenyl(C2-C6)alkyl (optionally substituted with one or more R1), heteroarylmethyl (optionally substituted with R1), cycloalkyl, cycloalkenyl, cycloalkylmethyl (where any carbon atom can be optionally replaced with N, S, or O and where said cycloalkylmethyl can be optionally substituted with OH, CF3, halo, alkoxy, alkyl, benzyloxy, or alkanoyioxy), cycloalkenylmethyl (where any carbon atom can be optionally replaced with N, S, or O and where said cycloalkylmethyl can be optionally substituted with OH, CF3, halo, alkoxy, alkyl, benzyloxy, or alkanoyioxy); or R5 and R8, together with the nitrogen atom to which R8 is attached, form a ring optionally substituted with R5; R9 is H, (CrC4)alkyl, or (C1-C4)alkyl-C(=O); tis 1, 2, or 3; and x 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 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. 6 WO 2005/037809 PCT/US2004/033990 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, nervous 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. [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. [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 or pharmaceutically acceptable salt thereof. [0020] In another embodiment, the present invention is directed to methods for treating or preventing gastrointestinal or genitourinary disorder, particularly stress 7 WO 2005/037809 PCT/US2004/033990 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 accompanying 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 norepinephrine and serotonin and their respective receptors (5-HT2a, ?? and ?2-adrenergic). DETAILED DESCRIPTION OF THE INVENTION [0026] The present invention is directed to substituted aryl cycloalkanoyl derivatives, compositions containing these derivatives, and methods of their use for 8 WO 2005/037809 . PCT/US2004/033990 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, nervous 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. "?°C" and ??"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. "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 inhibitor3' is abbreviated SNR1. "Serotonin reuptake inhibitor" is abbreviated SRI. "Selective serotonin reuptake inhibitor" is abbreviated SSRI. 9 WO 2005/037809 PCT/US2004/033990 "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. Varying 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 desired response in the individual, but also with factors such as the disease state or severity of tho 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 10 WO 2005/037809 PCT/US2004/033990 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 time 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. [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. 11 WO 2005/037809 PCT/US2004/033990 [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, benzenesulfonic, benzoic, camphorsulfonic, citric, ethenesulfonic, fumaric, gluconic, glutamic, 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. 12 WO 2005/037809 PCT/US2004/033990 [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-mcnopausal, 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. [0045] The term "pre-menopausal" 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 et al, 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 13 WO 2005/037809 PCT/US2004/033990 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, vomiting, nausea, sweating, and flushes (Janowsky, et al., Journal of Clinical Psychiatry, 1984, 45(10 Pt 2): 3-9). [0047] "Alkyl," as used herein, refers to an aliphatic hydrocarbon chain of 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 of 1 to 6 carbon atoms. [0049] "Alkoxycarbonyl," as used herein, refers to the group R-O-C(=O)- where R is an alkyl group of 1 to 6 carbon atoms. [0050] "Alkanoyl," as used herein, refers to the group R-C(=O)- where R is an alkyl group of 1 to 6 carbon atoms. [0051] "Alkanoyloxy," as used herein, refers to the group R-C(=O)-O- where R is an alkyl group of 1 to 6 carbon atoms. [0052] "Alkylaminocarbonyl," as used herein, refers to the group R-NH-C(=O)-where R is an alkyl group of 1 to 6 carbon atoms. [0053] "Alkylcarbonylamino," as used herein, refers to the group R-C(=O)-NH where R is an alkyl group of 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. 14 WO 2005/037809 PCT/US2004/033990 [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 optionally substituted. [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. [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, furyl, pyridyl, 1,2,4-thiadiazolyl, pyrimidyl, thienyl, isothiazolyl, imidazolyl, tetrazolyl, pyrazinyl, pyrimidyl, quinolyl, isoquinolyl, thiophenyl, benzothienyl, isobenzofuryl, pyrazolyl, indolyl, purinyl, carbazolyl, benzimidazolyl, and isoxazolyl. [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 15 WO 2005/037809 PCT/US2004/033990 atom in the heterocycle may optionally be quaternized. 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-pyrroIyl, 3H-indolyl, 4-piperidonyl, 4aH-carbazole, |4H-quinolizinyl, 6H-1,2,5-thiadiazinyl, acridinyl, azocinyl, benzimidazolyl, I benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, carbazolyl, 4H-carbazolyl, a-, (3-, or y-carbo\\ny\, 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, isoindazoyl, isoindolinyl, isoindoiyl, isoquinolinyl, isothiazolyl, isoxazolyl, morpholinyl, I 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, p,iperazinyl, piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazdinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, carbolinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6/-/-1,2,5-thiadiazinyi, 1, 2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazoIyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triaziny 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, pyralolyl, imidazolyl, indolyl, benzimidazolyl, 1 H-indazolyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, or isatinoyl. Also included are fused lring 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. 16 WO 2005/037809 PCT/US2004/033990 [0060] "Heteroarylmethyloxy," as used herein, refers to the group R-CH2-O- 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-O- 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. [0064] "Cycloalkylmethyl," as used herein, refers to the group R-CH2- where R is a cycloalkyl group, as defined herein. [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. [0066] "Cycloalkenylmethyl," as used herein, refers to the group R-CH2- where R is a cycloalkenyl group, as defined herein. 17 WO 2005/037809 PCT/US2004/033990 [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: or a pharmaceutical salt thereof; wherein: W is H or OR9; R1 is phenyl, naphthyl, heteroaryl, benzyloxy, phenoxy, naphthyloxy, phenylethoxy, phenoxyethoxy, naphthylmethoxy, naphthylethoxy, phenylcarbonylamino, phenylaminocarbonyl, trifluoromethoxy, nitrile, alkenyl, alkynyl, sulfonyl, sulfonamido, alkanoyl, alkoxycarbonyl, alkylaminocarbonyl, or amino; where said phenyl, naphthyl, heteroaryl, benzyloxy, phenoxy, naphthyloxy, phenylethoxy, phenoxyethoxy, naphthylmethoxy, naphthylethoxy, 18 WO 2005/037809 PCT/US2004/033990 phenylcarbonylamino, and phenylaminocarbonyl are optionally substituted with one or more R2; R2 is H, or one or two substituents, the same or different selected from OH, alkyl, alkoxy, halo, trifluoromethyl, alkanoyloxy, methylenedioxy, trifluoromethoxy, nitrile, nitro, alkenyl, alkynyl, sulfonyl, or sulfonamido; R5 is H, (C1-C6)alkyl, or trifluoromethyl; 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; where RG 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-C6)alkyl, hydroxy(C1-C6)alkyl, benzyl (optionally substituted with benzyloxy or phenyloxy), naphthylmethyl (optionally substituted with one or more R1), phenyl(C2-C6)alkyl (optionally substituted with one or more R1), heteroarylmethyl (optionally substituted with R1), cycloalkyl, cycloalkenyl, cycloalkylmethyl (where any carbon atom can be optionally replaced with N, S, or O and where said cycloalkylmethyl can be optionally substituted with OH, CF3, halo, alkoxy, alkyl, benzyloxy, or alkanoyloxy), cycloalkenylmethyl (where any carbon atom can be optionally replaced with N, S, or O and where said cycloalkylmethyl can be optionally substituted with OH, CF3, halo, alkoxy, alkyl, benzyloxy, or alkanoyloxy); or R5 and R8, together with the nitrogen atom to which R8 is attached, form a ring optionally substituted with R5; R9 is H, (C1-C4)alkyl, or (C1-C4)alkyl-C(=O); t is 1, 2, or 3; and x is O, 1, or 2. [0072] In certain preferred embodiments, W is H or OR9; R1 is phenyl, naphthyl, heteroaryl, benzyloxy, phenoxy, naphthyloxy, phenylethoxy, phenoxyethoxy, naphthylmethoxy, naphthylethoxy, phenylcarbonylamino, phenylaminocarbonyl, trifluoromethoxy, nitrile, alkenyl, 19 WO 2005/037809 PCT/US2004/033990 aikynvl. sulfonyl, sulfonamido, alkanoyl, alkoxycarbonyl, alkylaminocarbonyl, or amino; where said phenyl, naphthyl, heteroaryl, benzyloxy, phenoxy, naphthyloxy, phenylethoxy, phenoxyethoxy, naphthylmethoxy, naphthylethoxy, phenylcarbonylamino, and phenylaminocarbonyl are optionally substituted with one or more R2; R2 is R1, H, OH, alkyl, alkoxy, halo, trifluoromethyl, alkanoyloxy, methylenedioxy, trifluoromethoxy, nitrile, nitro, alkenyl, alkynyl, sulfonyl, or sulfonamido; R5 is H, (C1-C6)alkyl or trifluoromethyl; R6 and R7 together form a ring of 4 to 8 carbon atoms; R8 is H, (C1-C6)alkyl, hydroxy(C1-C6)alkyl, benzyl (optionally substituted with benzyloxy or phenyloxy), naphthylmethyl (optionally substituted with one or more R'), phenyl(C2-C6)alkyl (optionally substituted with one or more R1), heteroarylmethyl (optionally substituted with R1), cycloalkyl, cycloalkenyl, cycloalkylmethyl (where any carbon atom can be optionally replaced with N, S, or O and where said cycloalkylmethyl can be optionally substituted with OH, CF3, halo, alkoxy, alkyl, benzyloxy, or alkanoyloxy), cycloalkenylmethyl (where any carbon atom can be optionally replaced with N, S, or O and where said cycloalkylmethyl can be optionally substituted with OH, CF3l halo, alkoxy, alkyl, benzyloxy, or alkanoyloxy); or R5 and R8, together with the nitrogen atom to which R8 is attached, form a ring optionally substituted with R5; R9 is H; t is 1, or 2; and x is 1 or 2. [0073] In certain preferred embodiments, W is OR9; R1 is phenyl, naphthyl, heteroaryl, benzyloxy, phenoxy, naphthyloxy, phenylethoxy, phenoxyethoxy, naphthylmethoxy, or naphthylethoxy; 20 WO 2005/037809 PCT/US2004/033990 where said phenyl, naphthyl, heteroaryl, benzyloxy, phenoxy, naphthyloxy, phenylethoxy, phenoxyethoxy, naphthylmethoxy, and naphthylethoxy are optionally substituted with one or more R2; R2 is R1, H, OH, alkyl, alkoxy, halo, trifluoromethyl, alkanoyloxy, methylenedioxy, trifluoromethoxy, nitrile, nitro, alkenyl, alkynyl, sulfonyl, or sulfonamido; R5 is H, (CrC6)alkyl or trifluoromethyl; R6 and R7 together form a ring of 4 to 8 carbon atoms; R8 is H, (CrC6)alkyl, hydroxy(Ci-CG)alkyl, benzyl (optionally substituted with benzyloxy or phenyloxy), naphthylmethyl (optionally substituted with one or more R1), phenyl(C2-C6)alkyl (optionally substituted with one or more R1), hetcroarylmethyl (optionally substituted with R1), cycloalkyl, cycloalkenyl, cycloalkylmethyl (where any carbon atom can be optionally replaced with N, S, or O and where said cycloalkylmethyl can be optionally substituted with OH, CF3, halo, alkoxy, alkyl, benzyloxy, or alkanoyloxy), cycloalkenylmethyl (where any carbon atom can be optionally replaced with N, S, or O and where said cycloalkylmethyl can be optionally substituted with OH, CF3, halo, alkoxy, alkyl, benzyloxy, or alkanoyloxy); R9 is H, t is 1; and x is 1. [0074] In certain preferred embodiments, W is OR9; R1 is trifluoromethoxy, nitrile, alkenyl, or alkynyl; R2 is R1, H, OH, alkyl, alkoxy, halo, or trifluoromethyl; R5 is H, (C1-C6)alkyl or trifluoromethyl; R6 and R7 together form a ring of 4 to 8 carbon atoms; R8 is H, (CrC6)alkyl, hydroxy(CrC6)alkyl, benzyl (optionally substituted with benzyloxy or phenyloxy), naphthylmethyl (optionally substituted with one or more R1), phenyl(C2-Ce)alkyl (optionally substituted with one or more R1), heteroarylmethyl (optionally substituted with R1), cycloalkyl, cycloalkenyl, cycloalkylmethyl (where any carbon atom can be optionally replaced with N, S, or O and where said cycloalkylmethyl can be optionally substituted with OH, CF3, halo, alkoxy, alkyl, 21 WO 2005/037809 PCT/US2004/033990 benzvloxy, or alkanoyloxy), cycloalkenylmethyl (where any carbon atom can be optionally replaced with N, S, or O and where said cycloalkylmethyl can be optionally substituted with OH, CF3> halo, alkoxy, alkyl, benzyloxy, or alkanoyloxy); or R5 and R8, together with the nitrogen atom to which R8 is attached, form a ring optionally substituted with R5; R9 is H; t is 1; and x is 1. [0075] In certain preferred embodiments, W is OR9; R1 is trifluoromethoxy, nitrile, alkenyl, or alkynyl; R2 is R1, H, OH, alkyl, alkoxy, halo, or trifluoromethyl; R5 is (CrCG)alkyl or trifluoromethyl; R6 and R7 together form a ring of 4 to 8 carbon atoms; R8 is H or (CrC6)alkyl; R9 is H; t is 1; and x is 1. [0076] In certain preferred embodiments, R1 is phenyl, naphthyl, heteroaryl, benzyloxy, phenoxy, naphthyloxy, phenylethoxy, phenoxyethoxy, phenylcarbonylamino, phenylaminocarbonyl, trifluoromethoxy, nitrile, alkenyl, alkynyl, sulfonyl, sulfonamido, alkanoyl, alkoxycarbonyl, alkylaminocarbonyl, or amino. [0077] In certain preferred embodiments, R2 is H, OH, alkyl (especially methyl, ethyl, propyl, and butyl), alkoxy (especially methoxy and ethoxy), halo (especially chloro, fluoro, and bromo). [0078] In certain preferred embodiments, R5 is H, (d-CG)alkyl (especially methyl, ethyl, propyl, and butyl), halo (especially chloro, fluoro, and bromo). 22 WO 2005/037809 PCT/US2004/033990 [0079) In certain preferred embodiments, R6 and R7 are, independently, (Cr CG)alkyl (especially methyl, ethyl, propyl, and butyl) or (C3-C6)cycloalkyl (especially cyclopropyl, cyclobutyl, and cyclohexyl). [0080] In certain preferred embodiments, R6 and R7 can together form a ring of 4 to 8 carbon atoms. [0081] In certain preferred embodiments, R8 is H, (Ci-C6)alkyl (especially methyl, ethyl, propyl, and butyl), hydroxybutyl, benzyl, naphthylmethyl, phenyl(C2-C6)alkyl, heteroarylmethyl, cycloalkyl (especially cyclopropyl, cyclobutyl, and cyclohexyl), cycloalkenyl, cycloalkylmethyl, cycloalkenylmethyl. [0082] In certain preferred embodiments, R5 and R3, together with the nitrogen atom to which R8 is attached, form a ring optionally substituted with R5. [0083] In certain preferred embodiments, R9 is H or (CrC^alkyl (especially methyl and ethyl). [0084] In certain preferred embodiments, t is 1. In certain other preferred embodiments, t is 2. In yet certain other embodiments, t is 3. [0085] In certain preferred embodiments, x is 0. In certain other preferred embodiments, x is 1. In yet certain other preferred embodiments, x is 2. Examples of R6 and R7 together with the carbon to which they are attached include 4, 5 or 6 carbon rings, e.g. a cyclohexyl ring. Examples of R1 include trifluoromethoxy; thienyl; phenoxy; phenylethoxy; naphthyloxy; naphthylmethoxy; naphthylethoxy; alkenyl of 2 to 6 carbon atoms; alkynyl of 2 to 6 carbon atoms; phenyl optionally substituted by one, two or three substituents selected from halo, methylenedioxy, nitrile, nitro, alkoxy of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 23 WO 2005/037809 PCT/US2004/033990 carbon atoms trifluoromethoxy and trifluoromethyl; and benzyloxy optionally substituted by one or two substituents selected from halo, alkoxy of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms and trifluoromethyl. Examples of R2 are hydrogen, halo, alkoxy of 1 to 6 carbon atoms and hydroxy. R8 may be for example H, alkyl of 1 to 6 carbon atoms, hydroxy(d-C6)alkyl, benzyl, phenyl(C2-C6)alkyl and cycloalkylmethyl. W is for example OH. An example of x is 1. An example of t is 1. Each R5 is for example selected independently from H and alkyl of 1 to 6 carbon atoms. [0086] Preferred compounds of formula I include: 1 -{2-piperazin-1 -yl-1 -[3-(trifluoromethoxy)phenyl]ethyl}cycIohexanol dihydrochloride; 1 -{2-(4-methylpiperazin-1 -yl)-1 -[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{1 -[4-(benzyloxy)phenyl]-2-piperazin-1 -ylethyl}cyclohexanol dihydrochloride; 1 -{2-piperazin-1 -yl-1 -[4-(trif luoromethoxy)phenyl)ethyl}cyclohexanol dihydrochloride; 1 -{2-piperazin-1 -yl-1 -[3-(trif luoromethoxy)phenyl]ethyl}cyclobutanol dihydrochloride; 1-{1-[4-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol dihydrochloride; 1-[1-[4-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclobutanol dihydrochloride; 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclobutanol dihydrochloride; 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride; 1 -[1 -[3-(benzyloxy)phenyl]-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 24 WO 2005/037809 PCT/US2004/033990 1-{1-[3-(benzyloxy)phenylj-2-piperazin-1-ylethyl}cyclobutanol dihydrochloride; 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanoI dihydrochloride; 1-[1-(3',4'-dichloro-1,1'-biphGnyl-3-yl)-2-piperazin-1-ylethyl)cyclohexanol dihydrochloride; i-fi^S'^'-dichloro-i.i'-biphenyl-S-yl)-piperazin-i-ylethylJcyclohexanol dihydrochloride; 1-[1-(1,1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride; 1-[1-(4'-chloro-1,1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride; 1-[1-(4'-chloro-1,1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride; 1 -[1 -(3'-chloro-1,1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyljcyclohexanol dihydrochloride; 1-[1-(2'-fluoro-1,1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol maleate; 1 -[1 -(3',4'-difluoro-1,1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride; 1 -[1 -(3',4'-dichloro-1,1 '-biphenyl-2-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride; 1-[1-(1,1'-biphenyl-2-yl)-2-piperazin-1 -ylethyljcyclohexanol dihydrochloride; i-II^S'-chloro-l.T-biphenyl^-yl)^-piperazin-i-ylethyljcyclohexanol dihydrochloride; 1.-{1 -[2-(1,3-benzodioxol-5-yl)phenyl]-2-piperazin-1 -ylethyl}cyclohexanol dihydrochloride; 1-[2-(4-aminopiperidin-1-yl)-1-(3',4'-dichloro-1,1'-biphenyl-3-yl)ethyl]cyclohexanol dihydrochloride; i-fi^S'^'-dichloro-l.T-biphenyl-S-yl)-piperazin-i-ylethylJcyclobutanol dihydrochloride; 1-[1-CS'^'-dichloro-l.T-biphenyl-S-yl)-piperazin-i-ylethyljcyclobutanol dihydrochloride; 1-[1-(1,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1 -ylethyljcyclohexanol dihydrochloride; 1 -[1 -(3-cyanophenyl)-2-piperazin-1 -ylethyljcyclohexanol dihydrochloride; 25 WO 2005/037809 PCT/US2004/033990 1-[1-(3-cyanophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride; . 1 -[2-piperazin-1 -yl-1 -(3-vinylphenyl)ethyl]cyclohexanol dihydrochloride; 1-[2-piperazin-1-yl-1-(4-vinylphenyl)ethyl]cyclohexanol dihydrochloride; 1-[2-piperazin-1-yl-1-(4-prop-1-ynylphenyl)ethyl]cyclohexanol dihydrochloride; 1-[1-(2'-chloro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride; 1-[1-(3'-fluoro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride; 1-[1-(3'-chloro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride; 1 -[1 -(3'-cyano-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyljcyclohexanol dihydrochloride; 1 -[1 -(3'-nitro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride; 1-[1-(3'-methoxy-1.1'-biphenyl-yl)-piperazin-i-ylethyllcyclohexanol dihydrochloride; 1-{2-piperazin-1-yl-1-[3'-(trifluoromethoxy)-1,1'-biphenyl-4-yl]ethyl}cyclohexanol dihydrochloride; 1-[1-(4'-chloro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol . dihydrochloride; 1 -[1 -(3',4'-dichloro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyljcyclohexanol dihydrochloride; 26 WO 2005/037809 PCT/US2004/033990 1-[2-piperazin-1-yl-1-(4-thien-3-ylphenyl)ethyl]cyclohexanol dihydrochloride; 1 -[1 -(2'-chloro-1,1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 1 -[1 -(3'-chloro-1,1 '-biphonyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 1-[1-(3'-cyano-1>1'-biphenyl-4-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride; 1-[2-(4-methylpiperazin-1-yl)-1-(3'-nitro-1,1l-biphenyl-4-yl)ethyl]cyclohexanol dihydrochloride; 1 -[1 -(3'-methoxy-1,1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 1-[1-(4'-fluoro-1,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride; 1 -[1 -(4'-methyl-1,1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 1-[1-(3'-chloro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclobutanol dihydrochloride; 1 -{2-piperazin-1 -yl-1 -[3'-(trifluoromethoxy)-1,1 '-biphenyl-4-yl]ethyl}cyclobutanol dihydrochloride; 1 -[1 -(3',4'-dichloro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyclobutanol dihydrochloride; 1 -[1 -(3',5'-dichloro-1,1 '-bipheny!-4-yl)-2-piperazin-1 -ylethyljcyclobutanol dihydrochloride; 1-{(1S)-2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{(1 R)-2-piperazin-1 -yl-1 -[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{(1 S)-2-(4-methylpiperazin-1 -yl)-1 -[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1-{(1R)-2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -[1 -(3',4'-dichloro-1,1 '-biphenyl-3-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 27 WO 2005/037809 PCT/US2004/033990 1-{2-piperazin-1-yl-1-[3l-(trifluoromethoxy)-1,1l-biphenyl-3-yl]ethyl}cyclohexanol dihydrochloride; 1-{2-piperazin-1-yl-1-[4l-(trifluoromethyl)-1,1'-biphenyl-3-yl]ethyl}cyclohexanol dihydrochloride; i-fi^S'^'-dimethoxy-i.i'-biphenyl-S-yl)^-piperazin-i-ylethylJcyclohexanol dihydrochloride; -{1-[6-methoxy-3'-(trifluoromethoxy)-1,1'-biphenyl-3-yl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride; 1 -[1 -(3',4'-dichloro-6-methoxy-1,1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride; 1-{1-[6-methoxy-4'-(trifluoromethyl)-1,1'-biphenyl-3-yl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride; 1-[1-(6-methoxy-1,1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride; 1-[1-(3',4'-dichloro-6-methoxy-1,1'-biphenyl-3-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride; 1 -[1 -[6-methoxy-3'-(trif luoromethoxy)-1,1 '-biphenyl-3-yl]-2-(4-methy!piperazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 1-[1-[6-methoxy-4'-(trifluoromethyl)-1,1'-biphenyl-3-yl]-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride; 1-{1-[4-(benzyloxy)-3-(trifluoromethyl)phenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride; 1 -[1 -[4-(benzyloxy)-3-(trifluoromethyl)phenyl]-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 1 -[1 -[4-(benzyloxy)-3-bromophenyl]-2-(4-methylpipcrazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 2-(benzyloxy)-5-[1 -(1 -hydroxycyclohexyl)-2-piperazin-1 -ylethyljbenzonitrile dihydrochloride; 2-(benzyloxy)-5-[1 -(1 -hydroxycyclohexyl)-2-(4-methylpiperazin-1 -yl)ethyl]benzonitrile dihydrochloride; 1-{1-[4-(benzyloxy)-3-(trifluoromethoxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride; 28 WO 2005/037809 PCT/US2004/033990 1 -{2-(4-methylpiperazin-1 -yl)-1 -[4-(trifluoromethoxy)phenyl]ethyl} cyclohexanol dih'ydrochloride; 1-{2-[4-(1,3-benzoioxol-5-ylmethyl)piperazin-1-yl]-1-[4-(trifluoromethoxy)phenyl]ethyl} cyclohexanol dihydrochloride; 1-{2-[4-(cyclohexylmethyl)piperazin-1-yl]-1-[4-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{2-(4-ethylpiperazin-1 -yl)-1 -[4-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1 -{2-[cis-3,5-dimethylpiperazin-1 -yl]-1 -[4-(trifluoromethoxy)phenyl]ethyl}cyc!ohexanol dihydrochloride; 1-[1-(2'-fluoro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride; 4'-[1-(1-hydroxycyclohexyl)-2-piperazin-1-ylethyl]-1,1'-biphonyl-2-carbonitrile dihydrochloride; 1-[1-(2',5l-dichloro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride; 1 -{1 -[4-(benzyloxy)-3-chlorophenyl]-2-piperazin-1 -ylethyl}cyclohexanol dihydrochloride; 1-[1-[4-(benzyloxy)-3-chlorophenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol dihydrochloride; 1 -[1 -(3'-chloro-1,1 '-biphenyI-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclobutanol dihydrochloride; 1 -{2-(4-methylpiperazin-1 -yl)-1 -[3'-(trif luoromethoxy)-1,1 '-biphenyl-4-yl]ethyl}cyclobutanol dihydrochloride; 1 -[1 -(3',4'-dichloro-1,1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclobutanol dihydrochloride; 1-[1-(3',5'-dichloro-1,1l-biphenyl-4-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclobutanol dihydrochloride; 1 -[1 -(3-ethynylphenyl)-2-piperazin-1 -ylethyljcyclohexanol dihydrochloride; 1 -[1 -(3-ethynylphenyl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 1-[2-piperazin-1-yl-1-(3-prop-1-ynylphenyl)ethyl]cyclohexanol dihydrochloride; 29 WO 2005/037809 PCT/US2004/033990 1-[2-(4-methylpiperazin-1-yl)-1-(3-prop-1-ynylphenyl)ethyl]cyclohexanoi dihyt/rochloride; 1 -{2-(4-benzy I-1,4-diazepan-1 -yl)-1 -[4-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride; 1-{2-piperazin-1-yl-1-[4-(trifluoromethoxy)phenyl]ethyl}cyclobutanol dihydrochloride; 1-{2-(4-methyl-1,4-diazepan-1-yl)-1-[4-(trifluoromethoxy) phenyl]ethyl)cyclobutanol dihydrochloride; 1-[1-(4-phenoxyphenyl)-2-piperazin-1-ylethyl]cycohexanol dihydrochloride 1-[2-(4-methylpiperazin-1-yl)-1-(4-phenoxyphenyl)ethy]cyclohexanol dihydrochloride; 1-[2-[4-(cyclohexylmethyl)piperazin-1-yl]-1-(4-phenoxyphenyl)ethyl] cyclohexanol dihydrochloride; 1-[1-(3-phenoxyphonyl)-2-piperazin-1-ylethyl]cycohexanol dihydrochloride; 1-[2-(4-methylpiperazin-1-yl)-1-(3-phenoxyphenyl)ethy]cyclohexanol dihydrochloride; 1-[2-[4-(cyclohexylmethyl)piperazin-1-yl]-1-(3-phenoxyphenyl)ethyl] cyclohexanol dihydrochloride; 1-[2-(4-methyl-1-piperazinyl)-1-[4-phenylmethoxy)phenyl)ethyl]cyclohexanol dihydrochloride; 1-{(1R)-1-[4-(benzyloxy)-3-chlorophenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride; 1-{(1S)-1-[4-(benzyloxy)-3-chlorophenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride; 1 -[(1 R)-1 -[4-(benzyloxy)-3-chlorophenyl]-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride; 1-[(1S)-1-[4-(benzyloxy)-3-chlorophenyl]-2-(4-methylpiperazin-1-yl)cthyl]cyclohexanol dihydrochloride; 1-{(1S)-2-[4-(3-phenylbutyl)piperazin-1-yl]-1-[3-(trifluoromethoxy)phenyl] ethyl}cyclohexanol; 1 -{(1 S)-2-[(3S)-3-methylpiperazin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl] ethyl}cyclohexanol; 30WO 2005/037809 PCT/US2004/033990 1-[1-[4-(benzyloxy)-3-bromo-5-methoxyphenyl]-2-(4-mGthylpiperazin-1-yl)ethy/]cyclohexanol; 1-{1-[4-(benzyloxy)-3,5-dibromophenyl]-2-piperazin-1-ylethyl} cyclohexanol; 1-[1-[4-(benzyloxy)-3,5-dibromophenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol; (3R)-3-methyl-1-{2-piperazin-1-y!-1-[3-(trifluoromethoxy)phenyl]ethyl} cyclopentanol; (3R)-3-methyl-1 -{2-(4-methylpiperazin-1 -yl)-1 -[3-(trifluoromethoxy)phenyl] ethyl}cyclopentanol; 2,2-dimethyl-1-{2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl] ethyl}cyclopentanol; 2,2-dimethyl-1-{2-(4-methylpiperazin-1-yl)-1-[3-(triiluoromethoxy)phenylJ ethyljcyclopentanol; 1 -{2-(4-methylpiperazin-1 -yl)-1 -[4-(1 -naphthyloxy)phenyl]ethyl} cyclohexanol; 4-[1 -(1 -hydroxycyclohexyl)-2-piperazin-1 -ylethyl]-2-(trifluoro methoxy)phenol; 4-[1 -(1 -hydroxycyclohexyl)-2-(4-methylpiperazin-1 -yl)ethyl]-2-(trifluoromethoxy)phenol; 1 -{1 -[4-methoxy-3-(trifluoromethoxy)phenyl]-2-piperazin-1 -ylethyl}cyclohexanol; 1-[1-[4-methoxy-3-(trifluoromethoxy)phenyl]-2-(4-methylpiperazin-1-' yl)ethyl]cyciohexanol; 1-{1-[4-ethoxy-3-(trifluoromethoxy)phenylJ-2-piperazin-1-ylethyl}cyclohexanol; 1-[1-[4-ethoxy-3-(trifluoromethoxy)phenyl]-2-(4-methylpiperazin-1- yl)ethyl]cyclohexanol; • 1 -{1 -[4-isobutoxy-3-(trifluoromethoxy)phenyl]-2-piperazin-1 - ylethyl}cyclohexanol; 1 -[1 -[4-isobutoxy-3-(trifluoromethoxy)phenyl]-2-(4-methylpiperazin-1 - yl)ethyl]cyclohexanol; 1 -[1 -[4-(benzyloxy)-3-(trifluoromethoxy)phenyl]-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol; 1 -{1 -[4-(2-phenylethyl)phenyl]-2-piperazin-1 -ylethyl}cyclohexanol; 1-{2-(4-methylpiperazin-1-yl)-1-[4-(2-phenylethyl)phenyl]ethyl} cyclohexanol; 1-[(1S)-1-[4-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl] cyclohexanol; 32 WO 2005/O37809 PCT/US2004/03399O 1-{(1S)-2-[(3S)-3,4-dimethylpiperazin-1-yl]-1-[3-(trifluoromethoxy)phenyl] ethyijcyclohexanol; 1-{(1S)-2-(3-ethylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl] ethyl}cyclohexanol; 1-{(1S)-2-[(3S)-3-ethyl-4-methylpiperazin-1-yl]-1-[3-(trifluoromethoxy) phenyl]ethyl}cyclohexanol; 1-{(1S)-2-[(3R)-3-ethyl-4-methylpiperazin-1-yl]-1-[3-(trifluoromethoxy) phenyl]e(hyl}cyclohexanol; 1-[(1S)-1-(3-phenoxyphenyl)-2-piperazin-1-ylethyl]cyclohexanol; 1-[(1R)-1-(3-phenoxyphenyl)-2-piperazin-1-ylethyl]cyclohexanol; 1-{2-(4-isopropylpiperazin-1-yl)-1-[3-(trifluoromethoxy) phenyl]ethyl}cyclohoxanol; 1-{(1S)-2-{4-[(1S)-1-phenylethyljpiperazin-1-yl}-1-[3-(trifluoromethoxy) phenyl]ethyl}cyclohexanol; 1-{(1S)-2-{4-[(1R)-1-phenylethyl]piperazin-1-yl}-1-[3-(trifluoromethoxy) phenyl]ethyl}cyclohexanol; 1-{(1S)-2-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-1-[3-(trifluoromethoxy) phenyljethyljcyclohexanol; 1 -{(1 S)-1 -[3-(trifluoromethoxy)phenyl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl]ethyl}cyclohexanol; 1 -{(1 S)-2-[(3R)-3-methylpiperazin-1 -ylj-1 -[3-(trifluoromethoxy)phenyl] ethyl}cyclohexanol; 1 -{(1 S)-2-[(3R)-3,4-dimethylpiperazin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl] ethyl}cyclohexanol; 1 -{(1 S)-2-(octahydro-2H-pyrido[1,2-a]pyrazin-2-yl)-1 -[3-(trifluoromethoxy) phenyl]ethyl}cyclohexanol; 1-{2-[4-(2-hydroxy-2-methylpropyl)piperazin-1-yl]-1-[3-(trifluoromethoxy) phenyl]ethyl}cyclohexanol; 1-{2-[4-(2-hydroxy-1,1-dimGthylethyl)piperazin-1-yl]-1-[3-(trifluoromethoxy) phenyl]ethyl}cyclohexanol; 1-{1-[4-(1-naphthyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol; 1-{1-[4-(benzyloxy)-3-bromo-5-mothoxyphenyl]-2-piperazin-1-ylethyl}cyclohexanol; 31 WO 2005/037809 PCT/US2004/033990 1-[(1B)-1-[4-(ben-zyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol; 1-{1-[4-(benzyloxy)-3-fluorophenyl]-2-piperazin-1-ylethyl}cyclohexanol; 1-[1-[4-(benzyloxy)-3-fluorophenyl]-2-(4-methylpiperazin-1-y|)ethyl]cyclohexanol; 1 -[1 -(3-fluoro-4-{[4-(trifluoromethyl)benzyl]oxy}phenyl)-2-piperazin-1 -ylethyl]cyclohexanol; 1-[1-(3-fluoro-4-{[4-(trifluoromethyl)benzyl]oxy}phenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol; 1-(1-{3-fluoro-4-[(4-methylbenzyl)oxy]phenyl)-2-piperazin-1-ylethyl)cyclohexanol; 1 -[1 -{3-fluoro-4-[(4-methylbenzyl)oxy]pheny)}-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol; 1 -[1 -(3-chloro-4-{[4-(trifluoromethyl)benzyl]oxy}phenyl)-2-piperazin-1 -ylethyl]cyclohexanol; 1 -[1 -(3-chloro-4-{[4-(trifluoromethyl)benzyl]oxy}phenyl)-2-(4-methylpiperazin- 1 -yl)ethyl]cyclohexanol; 1-[1-(3-chloro-4-{[2-(trifluoromethyl)benzyl]oxy}phenyl)-2-piperazin-1-ylethyl]cyclohexanol; 1-[1-(3-chloro-4-{[2-(trifluoromethyl)benzyl]oxy}phenyl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol; 1 -[1 -(3-chloro-4-{[3-(trifluoromethyl)benzyl]oxy}phenyl)-2-piperazin-1 -ylethyl]cyclohexanol; 1-[1-(3-chloro-4-{[3-(trifluoromethyl)benzyl]oxy}phenyl)-2-(4-methylpiperazin- 1 -yl)ethyl]cyclohexanol; 1 -(1 -{4-[(4-bromo-2-fluorobenzyl)oxy]-3-chlorophenyl}-2-piperazin-1 -ylethyl)cyclohexanol; 1 -[1 -{4-[(4-bromo-2-fluorobenzyl)oxy]-3-chlorophenyl}-2-(4-methylpiperazin-1 - yl)ethyl]cyclohexanol; 1 -{1 -[3-chloro-4-(2-naphthylmethoxy)phenyl]-2-piperazin-1 -ylethyl} cyclohexanol; 1 -{1 -[4-(2-naphthylmethoxy)phenyl]-2-piperazin-1 -ylethyljcyclohexanol; 1-{2-(4-methylpiperazin-1-yl)-1-[4-(2-naphthylmethoxy)phenyl] ethyl}cyclohexanol; 33 WO 2005/037809 PCT/US2004/033990 1 -(1 -{4-[(4-bromo-2-f luorobenzyl)oxy]phenyl}-2-piperazin-1 -yle"thyi)cyclohexanol; 1-[1-{4-[(4-bromo-2-fluorobenzyl)oxy]phenyl}-2-(4-methylpiperazin-1-yi)ethyl]cyclohexanol; 1 -[2-piperazin-1 -yl-1 -(4-{[4-(trifluoromethyl)benzyl]oxy}phenyl) ethyljcyclohexanol; 1 -[2-(4-methylpiperazin-1 -yl)-1 -(4-{[4-(trifluoromethyl)benzyl]oxy} phenyl)ethyl]cyclohexanol; 1 -[2-piperazin-1 -yl-1 -(4-{[3-(trifluoromethyl)benzyl]oxy}phenyl) ethyljcyclohexanol; 1 -[2-(4-methylpiperazin-1 -yl)-1 -(4-{[3-(trifluoromethyl)benzyl]oxy} phenyl)ethyl]cyclohexanol; 1 -[2-piperazin-1 -yl-1 -(4-{[2-(trifluoromethyl)benzyl]oxy} phenyl)ethyl]cyclohexanol; 1 -[2-(4-methylpiperazin-1 -yl)-1 -(4-{[2-(trif luoromethyl)benzyl] oxy}phenyl)ethyl]cyclohexanol; 1 -{1 -[4-(benzyloxy)-3-methoxyphenyl]-2-piperazin-1 -ylethyl}cyclohoxanol; 1 -[1 -[4-(benzyloxy)-3-methoxyphenyl]-2-(4-methylpiperazin-1 -yl)ethyl] cyclohexanol; 1 -{1 -[3-methoxy-4-(2-naphthylmethoxy)phenyl]-2-piperazin-1 -ylethyl} cyclohexanol; 1-[1-[3-methoxy-4-(2-naphthylmethoxy)phenyl]-2-(4-methylpiperazin-1- yl)ethyl]cyclohexanol; 1 -(1 -{4-[(4-bromo-2-f luorobenzyl)oxy]-3-methoxyphenyl}-2-piperazin-1 - ylethyl)cyclohexanol; 1-[1-{4-[(4-bromo-2-fluorobenzyl)oxy]-3-methoxyphenyl}-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol; 1 -[1 -(3-methoxy-4-{[4-(trifluoromethyl)benzyl]oxy}phenyl)-2-piperazin-1 -ylethyljcyclohexanol; 1-[1-(3-methoxy-4-{[4-(trifluoromethyl)benzyl]oxy}phenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol; 1-{1-[3-chloro-4-(2-phenylethoxy)phenyl]-2-piperazin-1 -ylethyl} cyclohexanol; 34 PCT/US2004/033990 WO 2005/037809 1 -[1 -[3-chloro-4-(2-phenylethoxy)phenyl]-2-(4-methylpiperazin-1 - yl)ethy/jcyclohexanol; 1-(1-{3-chloro-4-[(3-methoxybenzyl)oxy]phGnyl}-2-piperazin-1-ylethyl)cyclohexanol; 1-[1-{3-chloro-4-[(3-methoxybenzyl)oxy]phenyl}-2-(4-methylpiperazin-1-yl)ethyllcyclohexanol; 1 -(1 -{3-chloro-4-[(2-methoxybenzyl)oxy]phenyl}-2-piperazin-1 -ylethyl)cyclohexanol; 1-[1-{3-chloro-4-[(2-methoxybenzyl)oxy]phenyl}-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol; 1-{1-[4-(2-phenylethoxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol; 1-{2-(4-methylpiperazin-1-yl)-1-[4-(2-phenylethoxy)phenyl] ethyl}cyclohexanol; 1 -(1 -{4-[2-(4-fluorophenyl)ethoxy]phenyl}-2-piperazin-1 -ylethyl) cyclohexanol; 1-[1-{4-[2-(4-fluorophenyl)ethoxy]phenyl}-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol; 1 -(1 -{4-[2-(1 -naphthyl)ethoxy]phenyl}-2-piperazin-1 -ylethyl)cyclohexanol; 1 -(2-(4-methylpiperazin-1 -yl)-1 -{4-[2-(1 -naphthyl)ethoxy]phenyl} ethyl)cyclohexanol; 1-[1-{4-[2-(4-methoxyphenyl)ethoxy]phenyl}-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol; 1-[1-[4-(cyclohexylmethoxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol; 1 -(2-(4-methylpiperazin-1 -yl)-1 -{4-[(1 R)-1 -phenylethoxy]phenyl} ethyl)cyclohexanol; 1-(2-(4-methylpiperazin-1-yl)-1-{4-[(1S)-1-phenylethoxy]phenyl} ethyl)cyclohexanol; and pharmaceutically acceptable salts thereof. [0087] Some of the compounds of the present invention may contain chiral centers and such compounds may exist in the form of stereoisomers (i.e. enantiomers). The present invention includes all such stereoisomers and any mixtures thereof including racemic mixtures. Racemic mixtures of the stereoisomers as well as the 35 WO 2005/037809 PCT/US2004/033990 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, including high performance liquid chromatography (HPLC) and the formation and crystallization of chiral salts or prepared by methods described herein. See, for example, Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen, S.H., et al., Tetrahedron, 33:2725 (1977); 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). [0088] The present invention includes prodrugs of the compounds of formula I. . "Prodrug," as used herein, means a compound which is convertible in vivo 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 (1985); Widder, et al. (ed.), Methods in Enzymology, vol. 4, Academic Press (1985); Krogsgaard-Larsen, et al., (ed). "Design and Application of Prodrugs," Textbook of Drug Design and Development, Chapter 5, 113-191 (1991), 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 (1975). [0089] 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. [0090] This invention also provides process for preparing a compound of formula I which includes one of the following: a) reducing a compound of formula 36 WO 2005/037809 PCT/US2004/033990 wherein R1, R2, R5'8, x, t and W are as defined herein to give a compound of formula I; if necessary any reactive groups or sites being protected during the reaction by protecting group(s) and removed thereafter; or b) alkylating a compound of formula I wherein R8 is hydrogen with an alkylating agent to give a compound of formula I wherein R8 is as defined herein excepting hydrogen ; 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. 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. 37 WO 2005/037809 PCT/US2004/033990 [00911 As will be readily understood, functional groups present may contain protecting 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. 38 [0092] 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. 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 1-5). WO 2005/037809 PCT/US2004/033990 Scheme 1 , where Y = H, R8j or P; P is an amine protecting group, preferably but not limited to tert-butoxycarbonyl; and R1, R2, R3, R4, R5, R6 R7, R8, W and x are as previously described. [0093] 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. Where P = fe/t-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. [0094] Compounds of formula VI can be prepared via the coupling of compounds of formula V with an appropriately substituted secondary or primary 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 substituted secondary or primary amine and triethylamine. [0095] Compounds of formula V are prepared by reacting an appropriately substituted ketone with a phenylacetic acid of formula IV via an aldol reaction. The phenylacetic acids of formula IV can be either commercially obtained or are known compounds that can be prepared by standard procedures 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 39 WO 2005/037809 PCT/US2004/033990 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 -809C to about -502C being preferred. 40 [0096] If it is desired to produce compounds of formula VIII, they can be formed from compounds of formula I, where Y = H, via an alkylation with an alkyl halide or via a reductive amination with an aldehyde or ketone. Any conventional method of alkylating a 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, when it is desired to form compounds of formula VIII where R8 = methyl, a mixture of the amine and formaldehyde in formic acid is heated at 60°C-80°C. If is desired to form compounds of formula VIII where R8 = lower alkyl other than methyl, a mixture of the amine and an appropriately substituted aldehyde or ketone in methylene chloride is treated with trisacetoxyborohydride. WO 2005/037809 PCT/US2004/033990 Scheme 3 [0097] If it is desired to produce compounds of formula X where R1 = nitrile, they can be formed from compounds of formula IX, where P = an amirie 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. [0098] Compounds of formula IX can be formed from compounds of formula VII where Ri = 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 41 tris(dibenzylideneacetone)dipalladium. This reaction is performed in high boiling point solvents such as N, N-dimethylformamide, under nitrogen, at elevated temperatures from 1000C to about 1500C being preferred. Compounds of formula VII are prepared in Scheme 1. If it is desired to form compounds of formula VIII from compounds of formula X, the procedure outlined in Scheme 2 can be followed. WO 2005/037809 PCT/US2004/033990 [0099] 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 R, = 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(triphenylphosphine)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 70qC to about 1005C being preferred. If it is desired to form compounds of formula VIII from compounds of formula XII, the procedure outlined in Scheme 2 can be followed. Scheme 5 where B = alkenyl or alkynyl. [0100] 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 42 WO 2005/037809 PCT/US2004/033990 from compounds of formula VII where Ri = 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 tetrakis(triphenylphosphine)palladium (0). This reaction is performed in high boiling point solvents such as N, /V-dimethylformamide or toluene, under nitrogen, at elevated temperatures from 90-C to about 1209C being preferred. Compounds of formula XIV arc formed from compounds of formula XIV as described in Scheme 1. If it is desired to form compounds of formula VIII from compounds of formula XIV, the procedure outlined in Scheme 2 can be followed. [0101] The compounds of formula I have an asymmetric carbon atom. In accordance with this invention 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 formula VII, where Y = P, or the amine of formula I or formula VIII via either High Performance Liquid Chromatography (HPLC) or via Supercritical Fluid Chromatography. [0102] The separation of R and S isomers can also be achieved by forming a lower alkyl 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 V (See, for 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. [0103] In other embodiments, the invention is directed to pharmaceutical compositions, comprising: 43 WO 2005/037809 PCT/US2004/033990 a. at least compound of. formula I or pharmaceuticaliy acceptable salt thereof; smd b. at least one pharmaceuticaliy acceptable carrier. Generally, the compound of formula I or a pharmaceuticaliy 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 pharmaceuticaliy 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 pharmaceuticaliy 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 pharmaceuticaliy acceptable salt thereof will be present at a level of at 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 pharmaceuticaliy 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. [0104] 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 (1985). Pharmaceuticaliy acceptable carriers are those that are compatible with the other ingredients in the formulation and biologically acceptable. [0105] 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 flavoring 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 44 WO 2005/037809 PCT/US2004/033990 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, s;odium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins. [0106] 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, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers, or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral 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. [0107] 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. [0108] Preferably the pharmaceutical composition 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 45 WO 2005/037809 PCT/US2004/033990 capsule or tablet itself, or it can be the appropriate number of any such compositions in package form. [0109] 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. [0110] 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 one or more compounds of the present invention. [0111] 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. [0112] 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, nasal, pulmonary, transdermal, such as passive or iontophoretic delivery, or parenteral, e.g. rectal, depot, subcutaneous, intravenous, intraurethral, intramuscular, intranasal, ophthalmic solution or an ointment. Furthermore, the administration of compound of formula I with other active ingredients may bo concurrent or simultaneous. [0113] It is believed that the present invention described presents a substantial 46 WO 2005/037809 PCT/US2004/033990 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, nervous 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. [0114] 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. 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, nervous 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. [0115] "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. [0116] The term "hot flush" is an art-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. [0117] The term "sexual dysfunction" includes, but is not limited to, condition relating to desire and/or arousal. 47 WO 2005/037809 PCT/US2004/033990 [0118] 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 involuntary voiding 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 involuntary 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 vulvodynia, prostatodynia, and proctalgia). [0119] 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. [0120] 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. [0121] As used herein, "nervous 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 nervosa, bulimia,nervosa, attention-deficit disorder 48 WO 2005/037809 PCT/US2004/033990 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 nervous 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 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). [0122] In one embodiment, the present invention's 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. [0123] 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) 49 WO 2005/037800 PCT/US2004/033990 (Figure 1). Accordingly, the estrogen deprivation may result in altered norepinephrine activity. [0124] 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 adrenergical and adrenergic^ 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-HT23 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 (Figure 2). [0125] 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 a2 receptor with an antagonist, or (iii) blocking the activity of 5-HT on NE neurons with a 5-HT2a antagonist. [0126] 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: administering to said subject an effective amount of at least one compound of formula I or pharmaceutically acceptable salt thereof. [0127] 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. 50 WO 2005/037809 PCT/US2004/033990 [0128] 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. [0129] 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. [0130] 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. [0131] 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. [0132] The pain may be, for example, acute pain (short duration) or chronic pain (regularly reoccurring or persistent). The pain may also be centralized or peripheral. [0133] 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 51 WO 2005/037809 PCT/US2004/033990 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. [0134] 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 nervous 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 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. [0135] 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 neuralgia, reflex sympathetic dystrophy, casualgia, thalamic syndrome, nerve root avulsion, or nerve damage cause by injury resulting in peripheral and/or central sensitization such as phantom limb pain, reflex sympathetic dystrophy or postthoracotomy 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. 52 WO 2005/037809 PCT/US2004/033990 [0136] 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 viscera! 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. Additionally, the chronic pain may be with or without peripheral or central sensitization. [0137] 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 [0138] 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 53 WO 2005/037809 PCT/US2004/033990 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 [0139] 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-butyllithium (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 tetrahydrofuran (20 mL). The reaction was then allowed to warm to 25 °C where it w.as stirred for 45 minutes and was then re-cooled to -78 °C. A solution of cyclohexanone (3.65 mL, 35.3 mL) in tetrahydrofuran (10 mL) was then added via cannula, and the resulting mixture was stirred at -78 °C 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 (1 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 yield 6.05 g (96%) of pure (3-chlorophenylV1-hvdroxvcvclohexvnacetic acid as a white solid. HRMS: calcd for C14H17CIO3, 268.0866; found (ESLFT), 291.0748. b) In an analogous manner, (3-bromophenyl)(1 -hydroxycyclohexyl)acetic acid was prepared from 3-bromophenylacetic acid and cyclohexanone. HRMS: calcd for C14H17BrO3, 312.0361; found (ESI_FT), 350.99924. c) In an analogous manner, (1 -hydroxvcvclobutyl)(2-naphthvl)acetic acid was prepared from 2-napthylacetic acid and cyclobutanone. HRMS: calcd for C16H16O3, 256.1099; found (ESI_FT), 279.09927. 54 WO 2005/037809 PCT/US2004/033990 d) In an analogous manner, 3,4-dichloro-alpha-(1-hvdroxycvclohexyl)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-hvdroxvcvclohexvl)(1-naphthyl)acetic acid was prepared from 1-napthylacetic acid and cyclohexanone. MS (ESI) m/z 283 ([M- H]"); HRMS: calcd for C18H2oO3, 284.1412; found (ESI_FT), 307.13001. f) In an analogous manner, (1-hvdroxvcvclohexyl)[3-(trifluoromethoxv)phenvllacetic acid was prepared from 3-trifluoromethoxyphenylacetic acid and cyclohexanone. HRMS: calcd for C15H17F3O4. 318.1079;-found (ESI), 317.1013. g) In an analogous manner, (1-hvdroxvcvclohexvl)f4-(trifluoromethoxv)phenyl1acetic acid was prepared from 4-trifluoromethoxyphenylacetic acid and cyclohexanone. MS (ESI) m/z 317 ([M-H]"). h) In an analogous manner, (4-bromophenvl)(1-hydroxvcvclohexyl)acetic acid was prepared from 4-bromophenylacetic acid and cyclohexanone. MS (ESI) m/z 313/315 ([M+H]+); Anal. Calcd for Cl4H17BrO3: 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-dichlorophenvl)(4-hydroxv-1-methvlpiperidin-4- yl)acetic acid was prepared from 3,4-dichlorophenylacetic acid and 1-methyl-4- piperidone. HRMS: calcd for C14H17Cl2NO3 HCI, 353.0352; found (ESLFT), 318.0653. j) In an analogous manner, (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid was prepared from 3-bromophenylacetic acid and cyclobutanone. HRMS: calcd for C12H13Br03, 284.0048; found (ESI_FT), 306.99337. k) In an analogous manner, (1-hvdroxvcvclobutyl)[3-(trifluoromethoxy)phenvl1acetic acid was prepared from 3-trifluoromethoxyphenylacetic acid and cyclobutanone. HRMS: calcd for C13H13F3O4, 290.0766; found (ESI), 289.0686. I) In an analogous manner, (3-bromo-4-methoxvphenvl)(1-hvdroxvcvclohexyl)acetic acid was prepared from 3-bromo-4-methoxyphenylacetic acid and cyclohexanone. MS (ESI) m/z 341/343 ([M-H]'); HRMS: calcd for C15H19BrO4, 342.0467; found (ESI_FT), 341.03897. m) In an analogous manner, (1-hvdroxvcvclohexvl)[3-(trifluoromethvl)phenyl]acetic acid was prepared from 3-trifluoromethylphenylacetic acid and cyclohexanone. 55 WO 2005/037809 PCT/US2004/033990 MS (ESI) m/z 301 ([M-H]-); HRMS: calcd for C15H17F3O3, 302.1130; found (ESL.FT), 325.1024. n) In an analogous manner, (4-benzyloxyphenvn(1 -hydroxycyclohexvPacetic acid was prepared from 4-benzyloxyphenylacetic acid and cyclohexanone. o) In an analogous manner, (1 -hydroxvcvclobutyl)(1 -naphthvPacetic acid was prepared from 1-napthylacetic acid and cyclobutanone. p) In an analogous manner, (3,4-dichlorophenyl)(1 -hydroxycyclobutvPacetic 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 -hydroxvcvclohexvl)(2-naphthvPacetic acid was prepared from 2-napthylacetic acid and cyclohexanone. HRMS: calcd tor C18H20O3, 284.1412; found (ESI_FT), 323.10414. r) In an analogous manner, (3-bromophenvl)(4-hydroxv-1-mothvlpiperidin-4- yl)acetic acid was prepared from 3-bromophenylacetic acid and 1-methyl-4- piperidone. HRMS: calcd for C14H18BrNO3 HCI, 363.0237; found (ESL_FT"), 328.05356. s) In an analogous manner, (1-hydroxvcvclopentyl)(1-naphthvPacetic acid was prepared from 1-napthylacetic acid and cyclopentanone. MS (ESI) m/z 269 ([M- H]); HRMS: calcd for C17H18O3, 270.1256; found (ESI_FT), 293.11485. t) In an analogous manner, 2-(3-bromophenyl)-3-ethvl-3-hvdroxvpentanoic 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 (ESI_FT), 323.02505. u) In an analogous manner, 2-(3-chlorophenvP-3-hvdroxv-3-propylhexanoic acid was prepared from 3-bromophenylacetic acid and 4-heptanone. MS (ESI) m/z 283/285 ([M+H]+); HRMS: calcd for C15H?1CIO3l 284.1179; found (ESI_FT), 307.1074. v) In an analogous manner, 2-(3-chlorophenvl)-3-ethvl-3-hydroxvpentanoic acid was prepared from 3-chlorophenylacetic acid and 3-pentanone. MS (ESI) m/z 255/257 ([M+H]+). w) In an analogous manner, 3-ethvl-3-hvdroxy-2-(1 -naphthyl)pentanoic acid was prepared from 1-napthylacetic acid and 3-pentanone. MS (ESI) m/z 271 ([M-H]). 56 WO 2005/037809 PCT/US2004/033990 x) \n an analogous manner, (4-hvdroxv-1-methvlpiperidin-4-vl)(2-naphthvl)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-methoxvphenyl)-3-ethyl-3-hydroxypentanoic acid was prepared from 3-bromo-4-methoxyphenylacetic acid and 3-pentanone. MS (ESI) m/z 329/331 ([M+H]+). z) In an analogous manner, (4-benzvloxyphenyl).(1 -hydroxycyclobutypacetic acid was prepared from 4-benzyloxyphenyIacetic acid and cyclobutanone. aa) In an analogous manner, (3-chlorophenvP(1-hydroxydecahvdronapthyl)ace1ic acid was prepared from 3-chlorophenylacetic acid and decahydronapthlene-1-one. MS (ESI) m/z321/323 ([M-H]"). bb) In an analogous manner, (3-bromo-4-methoxyphenvl)(4-tert-butvH-hydroxvcyclohexvnacetic acid was prepared from 3-bromo-4-methoxyphenylacetic acid and 4- tert-butylcyclohexanone. MS (ESI) m/z 397/399 ([M-H]"); HRMS: calcd for C19H27BrO4, 398.1,093; found (ESI_FT), 421.09875, cc) In an analogous manner, (3-chlorophenvl)(2-hvdroxvdecahvdronapthyl)ace1:ic acid was prepared from 3-chlorophenylacetic acid and decahydronapthlene-2-one. MS (ESI) m/z 321/323 ([M-H]"). dd) In an analogous manner, (4-tert-butvl-1-hydroxycyclohexyl)(1-naphthyl)acetic acid was prepared from 1-napthy-lacetic acid and 4- tert-butylcyclohexanone. MS (ESI) m/z 339 ([M-H]"); HRMS: calcd for C22H28O3, 340.2038; found (ESLFT), 363:19309. ee) In an analogous manner, (3-chlorophenyl)(4-hydroxvtetrahvdro-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-tert-butyl-1-hvdroxycvclohexyl)acetic acid was prepared from 3-bromophenylacetic acid and 4- terf-butylcyclohexanone. MS (ESI) m/z 367/369 ([M-H]"); HRMS: calcd for C18H25BrO3, 368.0987; found (ESLFT), 391.0878. gg) In an analogous manner, 2-(3-bromophenvn-3-hvdroxv-3-propvlhexanoic acid was prepared from 3-bromophenylacetic acid and 4-heptanone. MS (ESI) m/z 327/329 ([M+H]+). 57 WO 2005/037809 PCT/US2004/033990 hh) In an analogous manner, 2-(3-chlorophenvl)-3,3-dicvclopropvl-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-bromophenvP(1-hydroxv-3,3,5,5- tetramethylcyclohexyl)acetic acid was prepared from 3-bromophenylacetic acid and 3,3,5,5-tetramethylcyclohexanone. MS (ESI) m/z 367/369 ([M-H]"). jj) In an analogous manner, (4-ethyl-1-hvdroxvcvclohexyl) -(1-naphthyl) acetic acid was prepared from 1-napthylacetic acid and 4-ethylcyclohexanone. MS (ESI) m/z 311 ([M-H]'). kk) In an analogous manner, (3-chlorophenvP(4-tert-butvl-1-hvdroxvcyclohexyPacetic acid was prepared from 3-chlorophenylacetic acid and 4- tert- butylcyclohexanone. II) In an analogous manner, (4-methvl-1-hvdroxvcvclohexyl) -(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-bromophenvP(4-hvdroxvtetrahvdro-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 C13H15BrO4t 314.0154; found (ESI_FT), 315.02244. nn) In an analogous manner, (3-benzyloxyphenvl)(1 -hydroxycyclohexyl)acetic acid was prepared from 3-benzyloxyphenylacetic acid and cyclohexanone. oo) In an analogous manner, (3-bromophenvl)(2-hvdroxv-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-methoxvphenvP(4-hvdroxytetrahvdro-2H- pyran-4-ypacetic acid was prepared from 3-bromo-4-methoxyphenylacetic acid and tetrahydro-2H-pyran-4-one. MS (ESI) m/z 343/345 ([M-H]'); HRMS: calcd for C14H17Br05, 344.0259; found (ESI_FT), 367.01582. qq) In an analogous manner, (3-benzyloxyphenvP(1 -hydroxycyclobutyl)acetic acid was prepared from 3-benzyloxyphenylacetic acid and cyclobutanone. 58WO 2005/037809 PCT/US2004/O33990 rr) In an analogous manner,(5-chlorothien-2-yl)(1 -hvdroxvcyclohexyl)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-vl)(1-hvdroxvcvclohexyl)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 -hvdroxvcyclohexvl)acetic acid was prepared from 1-benzothien-3-yl acetic acid and cyclohexanol. MS (ESI) m/z 239 ([M-H]-) uu) In an analogous manner. (2-bromophenvl)(1-hvdroxycvclohexvl)acetic acid was prepared from 2-bromophenylacetic acid and cyclohexanol. MS (ESI) m/z 311/313 ([M-H]-) vv) In an analogous manner, (4-bromophenvl)(1 -hydroxycyclohexyl)acetic acid was prepared from 4-bromophenylacetic acid and cyclohexanone. MS (ESI) m/z 313/315 ([M+H]+); Anal. Calcd for C14Hl7Br03: 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-bromophenvn(1-hvdroxvcyclobutvl)acetic acid was prepared from 4-bromophenylacetic acid and cyclobutanone. xx) In an analogous manner, (1-methyl-1H-indol-3-yl) (1-hvdroxycylclohexyl) acetic acid was prepared from N-Methyl-3-indole acetic acid and cyclohexanone. yy) In an analogous manner, (1 -(tert-butyl-dimethvl-silanyl)-1 H-indol-3-yl) (1 - 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-hvdroxvcvclohexvl)(1.1'-biphenyl-4-vl)acetic acid was prepared from 4-biphenylacetic acid and cyclohexanone. MS (ESI) m/z 309 ([M- H]-) aaa) In an analogous manner(1-hvdoxvcyclobutvl)[4-trifluoromethoxy)phenvn acetic acid was prepared from 4-trifluoromethoxyphenyl acetic acid and cyclobutanone. MS (ESI) m/z 289 ([M-H]"). Solid-phase synthesis of polyamine spider toxins and correlation with the natural products by HPIC-MS/MS. Manov, Nikolay; Tzouros, Manuel; Chesnov, Sergiy; Bigler, Laurent; Bicnz, Stefan. Institute of Organic Chemistry, University of Zurich, Zurich, Switz. Helvetica Chimica Acta (2002), 85(9), 2827-28-16 59 WO 2005/037809 PCT/US2004/033990 bbb) Inian analogous manner (1-hvdoxvcvclohexvl)[4-phenoxyphenvll acetic acid was prepared from 4-phenoxyphenylacctic acid and cyclohexanone. MS (ESI) m/z 325 ([M-H]"). ccc) In an analogous manner (1-hvdoxvcyclohexvl)[3-phenoxvphenvl1 acetic acid was prepared from 3-phenoxyphenylacetic acid and cyclohexanone. MS (ESI) m/z 325 ([M-H]'). Anal. Calcd for C20H2204 0.1 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-(benzvloxy)-3-chlorophenvn( 1 - hydroxycyclohexyl)acetic acid was prepared from [4-(benzyloxy)-3- chlorophenyljacetic acid (DE 2556474, 1976, M.Kucher; B.Brunova; J. Grimova; N. Oldrich) and cyclohexanone. MS (ESI) m/z 373; fff) In an analogous manner, (1-naphthvl)(1-hvdroxvcycloheptvPacetic acid was prepared from 1-napthylacetic acid and cycloheptanone. ggg) In an analogous manner, 2-(3-chlorophenyl)-3-hvdroxv-3-methvlbutanoic acid was prepared from 3-chlorophenylacetic acid and acetone. MS (ES) m/z 226.9. hhh) In an analogous manner, (3-chlorophenvl)(1-hydroxv-3.3,5.5- tetramethvlcyclohexyl)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-hvdroxv-cvclohexyl)-(5-methoxv-benzo[b]thiophen-3-vl)- 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 C15H17F3O4, 318.1079; found (ESI), 317.1013. jjj) In an analogous manner, (2-hydroxydecahydronapthyl)(1-napthyl)acetic acid was prepared from 1-napthylacetic acid and decahydronapthlene-2-one. MS (ESI) m/z337 ([M-H]). kkk) In an analogous manner, (3-chlorophenvl)(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-(chloromethyl)dibenzyl (0.92 g, 4 mmol) and potassium cyanide (.039 g, 6 mmol) in N,N'-dimethylformamide (20 mL) was heated at 80 °C 60 WO 2005/037809 PCT/US2004/033990 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 yield 4; (phenethylphenyl)acetonitrile as an oil which was used in the next step without further purification. Step 2: 4-(Phenethylphenyl)acetonitrile from the above reaction was treated with a 6 N aqueous solution of hydrochloric acid (10 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. Trituration with hexane and fitration of the resulting solid afforded 0.64 g of 4-(2- phenylethyl)phenyl]nacetic acid as an off white solid. MS (ESI) m/z 239. Step3: In an analogous manner (as Reference Example l-a), (1- hvdroxvcvclohexvl)r4-(2-phenvlethyl)phenvnacetic 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 (1.30 g, 7.60 mmol) were added to a flask containing N,N- dimethylformamide (20 ml_). Potassium carbonate (1.25 g, 9.00mmol) was then added, and the solution was heated at 50 °C for 4 hours. A 2 N aqueous solution of sodium hydroxide (10 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 diethyl ether (2 x 50 mL). The combined ethereal layers were dried over magnesium sulfate and concentrated to afford 0.95 g of 4-benzyloxv-3-fluorophenvlacetic 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-(benzvloxv)-3-fluorophenyl](1-hvdroxvcyclohexvPacetic acid was prepared from [4-(benzyloxy)-3-fluorophenyl]acetic acid and cyclohexanone. MS (ESI) m/z 357. 61 WO 2005/037809 PCT/US20O4/O33990 nnn) Jn an analogous manner, [4-(benzyloxy)-3-methoxyphenyl](1- 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-chloio-4-r(3-methoxvbenzyl)oxviphenvl)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-methoxv-benzvloxvVphenylKI -hydroxy-cyclohexvOacetic acid was from {3-chloro-4-[(3-methoxybenzyl)oxy]phenyl}acetic acid and cyclohexanone. PPP) Step 1: In an analogous manner to Reference Example l-mmm, step 1 (3-chloro-4-f(2-methoxvbenzyl)oxviphenvl)acetic acid was prepared from {3-chloro-4-hydroxy-phenyl) acetic acid and 2-methoxybenzyl chloride .MS (ES) m/z 304.9. Step 2: In an analogous manner (as Reference Example l-a), [3-chloro-4-(2-methoxv-benzyloxv)-phenvll-(1 -hydroxy-cyclohexvP-acetic acid was from {3-chloro-4-[(2-methoxybenzyl)oxy]phenyl}acetic acid and cyclohexanone. qqq) In an analogous manner, [(3R)-1-hvdroxv-3-methylcyclopentvn[3-(trifluoromethoxy)phenvliacetic acid was prepared from (3-trifluoromethoxy-phenyl)-acetic acid and 3(R)-methyl-cyclopentanone. rrr) In an analogous manner, (1-hydroxv-2,2-dimethvl-cyclopentvlH3-trifluoromethoxv-phenyQ-acetic acid was prepared from (3-trifluoromethoxy-phenyl)-acetic acid and 2,2-dimethyl-cyclopentanone. sss) In an analogous manner, (1 -hvdroxvcvclohexvl)(6-methoxv-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, 13, 203-5) and cyclohexanone. MS (ES) m/z 313.0; HRMS: calcd for C19H22O4 + H+, 315.15909; found (ESI, [M+H]+), 315.159. ttt) In an analogous manner, (3-chloro-4-methoxvphenvl)-1(1-hvdroxvcyclohexvl) 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-hydroxvcyclohexvl)-(4- phenethyloxyphenyl) acetic acid was prepared from (4- phenethyloxyphenyl) acetic acid and cyclohexanone. MS(ESI) m/z 353 ([M-H]-) 62 WO 2005/037809 PCT/US2004/033990 vvv) Step 1: In an analogous manner to Reference Example l-mmm, step 1 (4-[2-(4-fluoro-phenyl)-ethoxv1-phenvl)-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-f2-(4-fluoro-phenvn-ethoxvl-phenyl}-(1 -hydroxy-cyclohexyD-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)-phenvH-acGtic acid was prepared from (4-hydroxyphenyl)acetic acid and 1-(2-bromoethyl)napthalene. MS(ESI) m/z 305 ([M-H]-). Step 2: In an analogous manner (as Reference Example l-a), (1-hydroxy-cyclohexyl)-f4-(2-naphthalen-1 -yl-ethoxv)-phenvl]-acetic acid was prepared from [4-(2-naphthalen-1-yl-ethoxy)-phenyl]-acetic acid and cyclohexanone. MS(ESI) m/z 403 ([M-H]") xxx) Step 1: In an analogous manner to Reference Example l-mmm, step 1 (4-[2-i'4-methoxy-phenvD-ethoxvi-phenyll-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), (1-hydroxy-cvclohexvl)-(4-f2-(4-methoxv-phenvl)-ethoxv1-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-cyclohexylmethoxv-phenyD-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-cyclohexylmethoxv-phenvl)-(1 -hydroxy-cyclohexyQ-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 03 WO 2005/037809 PCT/US2004/033990 triphenylphosphine (0.52 g , 0.002 mole) in anhydrous tetrahydrofuran (6 miL) was added dropwise over 15 minutes diisopropyl azodicarboxyiate (0.40 g, 0.002 mole) in tetrahydrofuran (16 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 (12 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-( (1F0-1-phenvlethoxyphenyl)acetic acid. MS(ESI) m/z 253 ([M-H]"). Step 2: In an analogous manner (as Reference Example l-a), (1-hydroxvcvclohexyl)-4-( (1R)-1-phenvlethoxvphenyl)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-( (1S)-1 -phenvlethoxvphenvPacetic 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 I-a), (1-hvdroxvcvclohexvl)-4-( (1S)-1-phenvlethoxvphenvl)acetic acid was prepared from 4-( (1S)-1-phenylethoxyphenyl)acetic acid and cyclohexanone. MS(ESI) m/z 353 ([M-H]-) 64 Example 1: 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cvclohexanol dihvdrochloride WO 2005/037809 PCT/US2004/033990 [0140] Step 1: A solution of (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) (5.4 g, 20.1 mmol), benzotriazol-1- yloxytris(dimethylam!no)phosphonium hexafluorophosphate (14.22 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 yield 7.10 g (81%) tert-butyl 4-[(3-chlorophenvl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate as a white foam. HRMS: calcd for C23H33ClN2O4, 436.2129; found (ESI_FT), 437.21996. [0141] Step 2: A solution of 4-[(3-ch!orophenyl)(1-hydroxycyclohexyl)acetyl]piperazine- 1-carboxylate (200 mg, 0.46 mmol) in dry tetrahydrofuran (3 mL) under nitrogen was treated dropwise with a solution of borane (1.0 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 (1 mL). The reaction was again heated at 70 °C for 1 h, and was then cooled and treated with methanol (1 mL). After the solvent was removed in vacuo, the resulting residue was dissolved in water (5 mL) and was washed with ethyl acetate (1 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 yield 146 mg (99%) 1 -[1 -(3-chlorophenyl)-2-piperazin-1 - ylethyl]cyclohexanol as a colorless oil. HRMS: calcd for C18H27CIN2O, 322.1812; found (ESI_FT), 323.18977. 1-[1-(3-Chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (146 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 yield 110 mg (60%) 1 -[1 -(3-chlorophenvl)-2-piperazin-1 - vlethvl]cvclohexanol dihydrochloride as a white solid.. MS (ESI) m/z 323/325 ([M+H]+); HRMS: calcd for C18H27C1N2O 2.00 HCI, 394.1345; found (ESl_FT), 323.18831; 65 WO 2005/037809 PCT/US2004/033990 Example 2: 1 -[2-(1,4'-bipiperidin-1 '-yl)-1 -(3-chlo,rophenvnethvncyclohexanol 66 dihydrochloride WO 2005/037809 PCT/US2004/033990 [0142] In an analogous manner to Example 1, step 1 1-f2-(1,4'-bipiperidin-1'-vl)-1-(3-chlorophenvl)-2-oxoethvncvclohexanol was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and N-(4-piperidine)piperidine. MS (ESI) m/z419/421 ([M+H]+); HRMS: calcd for C24H35CIN2O2> 418.2387; found (ESI), 419.2451. [0143] In an analogous manner to Example 1, step 2 1-[2-(1.4'-bipiperidin-1'-yl)-(3-chlorophenyl)ethyncyclohexanol dihydrochloride was prepared from 1 -[2-(1,4'-bipiperidin-1'-yl)-1-(3-chlorophenyl)-2-oxoethyl]cyclohexanol. MS (ESI) m/z 405/407 ([M+H]+); HRMS: calcd for C24H37CIN2O • 2.00 HCI, 476.2128; found (ESI), 405.2664. Example 3: 1 -f 1 -(3-chlorophenvl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -vl)ethyl]cvclohexanol dihydrochloride [0144] In an analogous manner to Example 1, step 1 1 -[ 1 -(3-chlorophenyl)-2-(4-pvrrolidin-1-vlpiperidin-1-vl)-2-oxoethvHcyclohexanol was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and 4-(1-pyrrolidinyl)piperidine. [0145] In an analogous manner to Example 1, step 2 1-f1-(3-chlorophenyl)-2-(4-pvrrolidin-1-vlpiperidin-1-vnethvl]cvclohexanoldihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -yl)-2-oxoethyl]cyclohexanol. MS (ESI) m/z 391/393 ([M+H]+); HRMS: calcd for C23H35CIN2O ¦ 2.00 HCI, 462.1971; found (ESI), 391.2497. Example 4: 1-[2-(1,4'-bipiperidin-1'-vl)-1-(3-bromophenvl)ethvl1cyclohexanol dihydrochloride . 67 WO 2005/037809 PCT/US2004/033990 [0146] In an analogous manner to Example 1, step 1 1-f2-(1,4'-bipiperidin-1'-yl)-1-(3-bromophenvl)-2-oxoethvllcyclohexanol 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 C24H3;,BrN2O2, 462.1882; found (ESI), 463.1975. [0147] In an analogous manner to Example 1, step 2 1-[2-(1,4'-bipiperidin-1'-yl)-1-(3-bromophenyl)ethvl1cvclohexanol dihydrochloride was prepared from 1 -[2-(1,4'-bipiperidin-1'-yl)-1-(3-bromophenyl)-2-oxoethyl]cyclohexanol. MS m/z 449/451 ([M+H]+); HRMS: calcd for C24H37BrN2O 2.00 HCI, 520.1623; found (ESI), 449.2149. Example 5: 1-f1-(2-naphthvl)-2-piperazin-1-vlethvl]cyclobutanol dihydrochloride [0148] In an analogous manner to Example 1, step 1 /erf-butyl 4-f(1- hvdroxvcvclobutvl)(2-naphthvl)acetyl1piperazine-1-carboxylate was prepared from (1-hydroxycyclobutyl)(2-naphthyl)acetic acid (Reference Example 1-c) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C^Hs^Oj, 424.2362; found (ESI_FT), 425.24337. [0149] In an analogous manner to Example 1, stop 2 1-[1-(2-naphthyl)-2-piperazin-1-vlethylicyclobutanol dihyrochloride was prepared from /erf-butyl 4-[(1- 68 WO 2005/037809 PCT/US2004/033990 hydroxycvclobutyl)(2-naphthyl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C20H20N2O • 2.00 HCI, 382.1579; found (ESI_FT), 311,21184. Example 6: 1-f2-(1 ¦4'-biniperidin-1'-vl)-1-(3.4-dichlorophenvl)ethvl)cvclohexanol dihydrochloridc [0150] In an analogous manner to Example 1, step 1 1-f2-(1.4'-bipiperidin-1'-yl)-1-(3,4-dichlorophenvl)-2-oxoethyl1cvclohexanol was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacGtic acid (Reference Example 1-d) and N-(4-piperidine)piperidine. [0151] In an analogous manner to Example 1, step 2 1 -[2-(1.4'-bipiperidin-1 '-yl)-1 -(3.4-dichlorophenyl)ethylicyclohexanol dihydrochloride was prepared from 1-[2-(1,4'-bipiperidin-1'-yl)-1-(3,4-dichlorophenyl)-2-oxoothyl]cyclohexanol. MS m/z 439/441/443 ([M+H]+); HRMS: calcd for C24H36CI2N2O • 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 [0152] In an analogous manner to Example 1, step 1 ¦ 1 -M-(3-bromophenyl)-2-oxo-2-(4-pvrrolidin-1-ylpiperidin-1-vl)ethyl)cvclohexanol was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-(1-pyrrolidinyl)piperidine. 69 WO 2005/037809 PCT/US2004/033990 MS (ESI) m/z 449 ([M+H]+); HRMS: calcd for C23H33BrN2O2, 448.1725; found (ESI), 449.1789: [0153] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenvl)-2-(4-pyrrolidin-1 -vlpiperidin-1 -yl)ethvlicyclohexanol dihvdrochloride was prepared from 1-[1-(3-bromophenyl)-2-oxo-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]cyclohexanol. MS m/z 435/437 ([M+H]+); HRMS: calcd for C23H35BrN2O • 2.00 HCI, 506.1466; found (ESI), 435.2021. Example 8: 1 -[2-(1,4'-bipiperidin-1 '-yl)-1 -(3-bromo-4-methoxyphenyl)ethyl]cyclohexanol dihydrochloride [0154] In an analogous manner to Example 1, step 1 1 -F2-(1,4'-bipiperidin-1 '-yl)-1 -(3-bromo-4-methoxvphenvl)-2-oxoethvl]cyclohexanol was prepared from (3-bromo-4-methoxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-1) and N-(4-piperidine)piperidine. [0155] In an analogous manner to Example 1, step 2 1 -[2-(1,4'-bipiperidin-1 '-yl)-1 -(3-bromo-4-methoxvphenvOethvHcvclohexanol dihvdrochloride was prepared from 1-[2-(1J4'-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 70 WO 2005/037809 PCT/US2004/033990 [0156] In an analogous manner to Example 1, step 1 1 -[1 -(3-bromo-4-methoxyphenyl)-2-(4-pvrrolidin-1-ylpiperidin-1-vl)-2-oxoethvl1cvclohexanol was prepared from (3-bromo-4-methoxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-1) and 4-(1-pyrrolidinyl)piperidine. [0157] In an analogous manner to Example 1, step 2 1 -M -(3-bromo-4-methoxvphenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -vl)ethvl]cvclohexanol 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-f2-(benzvlamino)-1-(3,4-dichlorophenyl)ethyl]cvclobutanol hydrochloride [0158] In an analogous manner to Example 1, step 1 A/-benzyl-2-(3,4-dichlorophenvO-2-(1 -hvdroxvcvclobutyl)acetamide was prepared from (3,4-dichlorophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-p) and benzylamine. HRMS: calcd for C19H19Cl2NO2, 363.0793; found (ESI.FT), 364.08658. [0159] In an analogous manner to Example 1, step 2 1 -[2-(benzylamino)-1 -(3.4-dichlorophenvQethyncyclobutanol hydrochloride was prepared from A/-benzyl-2-(3,4-dichlorophenyl)-2-(1-hydroxycyclobutyl)acetamide. HRMS: calcd for C1SH21CI2NO HCI, 385.0767; found (ESI_FT), 350.10832. 71 WO 2005/037809 PCT/US2004/033990 Example 11: 1-[1-(3.4-dichlorophenvl)-2-(4-pvrrolidin-1-vlpiperidin-1-yl)ethvlicvclohexanol dihydrochjoride [0160] In an analogous manner to Example 1, step 1 1 -[1 -(3,4-dichlorophenyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -vl)-2-oxoethyl]cvclohexanol was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and 4-(1-pyrrolidinyl)piperidine. [0161] In an analogous manner to Example 1, step 2 1 -f 1 -(3.4-dichlorophenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethylicyclohexanol 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-(benzvlamino)-1-(2-naphthvl)ethvllcyclonutanol hydrochloride [0162] In an analogous manner to Example 1, step 1 A/-benzyl-2-(1- hydroxvcvclobutyl)-2-(2-naphthvl)acetamide was prepared from (1-hydroxycyclobutyl)(2-naphthyl)acetic acid (Reference Example 1-c) and benzylamine. HRMS: calcd for C23H23NO2, 345.1729; found (ESI_FT), 346.17885. [0163] In an analogous manner to Example 1, step 2 1 -[2-(benzylamino)-1 -(2-naphthyDethvlicyclobutanol hydrochloride was prepared from A/-benzyl-2-(1- 72 WO 2005/037809 PCT/US2004/033990 hydroxycyc;!obutyl)-2-(2-naphthyI)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}cyclohexanol dihydrochloride [0164] Step 1: In an analogous manner to Example 1, step 1 fe/t-butyl (1-f(3,4-dichlorophenyl)(1-hvdroxvcvclohexvl)acetyl]piperidin-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 C24H34CI2N2O4, 484.1896; found (ESI), 485.1987. [0165] Step 2: A solution of tertrbutyl {1-[(3,4-dichlorophenyl)(1- hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate (364 mg, 0.75 mmol) in dry tetrahydrofuran (1 mL), under nitrogen, was treated with a solution of borane (1.0 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/hexane) WO 2005/037809 PCT/US2004/033990 hydroxycyoiobutyl)-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}cyclohexanol dihydrochloride [0164] Step 1: In an analogous manner to Example 1, step 1 fe/t-butyl (1-f(3,4-dichlorophenvl)(1-hvdroxvcvclohexyl]acetyl]piperidin-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 C24H34Cl2N2O4] 484.1896; found (ESI), 485.1987. [0165] Step 2: A solution of tert-butyl {1-[(3,4-dichlorophenyl)(1- hydroxycyclohexyl)acetyl]piperidin-4-yI}carbamate (364 mg, 0.75 mmol) in dry tetrahydrofuran (1 mL), under nitrogen, was treated with a solution of borane (1.0 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/hexane) to yield 187 mg (53%) ferf-butyl {1-[2-(3,4-dichIorophenyl)-2-(1- hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate as a white foam which eluted first and 88 mg (31%) 1-{1-(3,4-dichIorophenyl)-2-[4-(methylamino)piperidin-1- yl]ethyl}cyclohexanol as a colorless oil which eluted second, ferf-butvl (1-[2-(3,4-dichlorophenvl)-2-(1-hvdroxvcvclohexvl)ethyllpiperidin-4-vl)carbamate: MS (ES) m/z 471.3 ([M+KT); HRMS: calcd for C24H36CI2N2O3, 470.2103; found (ESI), 471.2165. ± (1-(3,4-dichlorophenvl)-2-r4-(methvlamino)piperidin-1-yl]ethvllcyclohexanol: MS m/z 385/387/389 ([M+H]+). 1-{1-(3,4-dichIorophenyl)-2-[4-(methylamino)pjperidin-1- 73 WO 2005/037809 PCT/US2004/O3399O yl]ethyl}cyclohexanol was converted to the dihydrochloride salt with a methanolic solution* of hydrochloric acid and diethyl ether to yield 45 mg (41%) 1-(1-(3.4-dichlorophenv0-2-f4-(methvlamino)piperidin-1-yl]ethvl)cvclohexanol dihydrochloride as a white solid. HRMS: calcd for C20H3oCI2N20 ¦ 2.00 HCI, 456.1269; found (ESI), 385.183. Example 14: 1-[2-(4-aminopiperidin-1-vl)-1-(3.4-dichlorophenyl]ethyllcvclohexanol dihvdrochloride [0166] A solution of terf-butyl {1-[2-(3,4-dichlorophenyl)-2-(1- hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate (130 mg, 0.28 mmol) (Example 13), in diethyl ether (2 mL) was treated with a 4 N solution of hydrogen chloride in dioxane (1 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 whore it was stored for an additional 16 h. The resulting crystals were collected, washed with diethyl ether, and dried in vacuo to yield 101 mg (82%) 1 -r,2-(4-aminopiperidin-1 -vl)-1 -(3.4-dichlorophenvOethyl]cvclohexanol dihvdrochloride as a white solid. MS m/z 371/373/375 ([M+H]+); HRMS: calcd for Ci9H26CI2N2O • 2.00 HCI, 442.1112; found (ESI), 371.1642. 74 Example 15: 4-[2-(benzylamino)-1-(3,4-dichlorophenyl)ethyl]-1-methylpiperidin-4-ol dihydrochloride WO 2005/037809 PCT/US2004/033990 [0171] In an analogous manner to Example 1, step 1 fort-butyl {1 -f (3-chlorophenvM1 -hydroxvcvclohexvl)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 C24H35CIN2O4, 450.2285; found (ESI), 451.2353. [0172] In an analogous manner to Example 13, step 2 1 -(1 -(3-chlorophenyl)-2-f4-(methylamino)piperidin-i -yllethyDcvclohexanol dihydrochloride was prepared from- tert-butyl (1-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS m/z 351/353 ([M+HD; 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 [0173] In an analogous manner to Example 1, step 1 tetf-butyl (1-f(3-bromophenyl)(1-hvdroxvcvclohexyl)acetyl]piperidin-4-vl|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. [0174] In an analogous manner to Example 13, step 2 ferf-butyl (i-[2-(3- bromophenvl)-2-(1-hvdroxycvclohexvl)ethyl]piperidin-4-yl]carbamate was prepared from 76 WO 2005/037809 PCT/US2004/033990 [0167] In an analogous manner to Example 1, step 1 N-benzvl-2-(3,4-dichlorophenyl)-2-(4-hvdroxv-1 -methvlpiperidin-4-yl]acetamide was prepared from (3,4-dichlorophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-i) and benzylamine. HRMS: calcd for C21H24Cl2N2O2, 406.1215; found (ESLFT), 407.12885. [0168] In an analogous manner to Example 1, step 2 4-f2-(benzvlamino)-1 -(3.4-dichloiophenvl)ethvl]-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 CsiH^C^O • 2.00 HCI, 464.0956; found (ESI_FT), 393.14924. Example 16: 1 -[2-f(3S)-3-aminopyrrolidin-1 -yll-1 -(3-chlorophenvl)ethyllcyclohexanol dihydrochloridc [0169] In an analogous manner to Example 1, step 1 ((S)-1 -f2-(3-Chloro-phenyl)-2-(1 -hvdroxv-cvclohexvl)-acetvl1-pvrrolidin-3-vl)-carbamic acid tert-butvl ester was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolodine. [0170] In an analogous manner to Example 1, step 2 1 -f2-[(3S)-3-aminopyrrolidin-1-vli-1 -Q-chlorophenvPethvllcvclohexanol dihvdrochloride 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 75 WO 2005/037809 PCT/US2004/033990 tert-butyl {1 -[(3-bromophenylphenyl)(1 -hydroxycyclohexyl)acetyl]piperidin-4- yljcarbamate. MS (ES) m/z 481.3 ([M+H]f); HRMS: calcd for C^HayBrNaOa, 480.1988; found (ESI), 481.2081. [0175] In an analogous manner to Example 14, H2-(4-aminopiperidin-1-vO-1-(3-bromophenyl)ethyl]cyclohexanol dihydrochloride was prepared from terf-butyl {1-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate. HRMS: calcd for Ci9H29BrN2O • 2.00 HCI, 452.0997; found (ESI), 381.1525. Example 19: 1-{1-(3-bromophenyl)-2-[4-(methyIamino)piperidin-1-yl]elhyl}cyclohexanol dihydrochloride [0176] In an analogous manner to Example 1, step 1 terf-butyl (1-f(3-bromophenyl)(1-hydroxvcyclohexvl)acetynpiperidin-4-vl)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. [0177] In an analogous manner to Example 13, step 2 1-{1-(3-bromophenyl)-2-[4-(methylarnino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride was prepared from /erf-butyl {1-[(3-bromophenylphenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS (ESI) m/z 395 ([M+H]+); HRMS: calcd for C2cH3iBrNoO • 2.00 HCI, 466.1153; found (ESI), 395.1708. Example 20: 1 -{2-(1,4'-bipiperidin-1 '-yl)-1 -[3-(trif luoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride 77 WO 2005/037809 PCT/US2004/033990 [0178] In an analogous manner to Example 1, step 1 1 -|2-(1,4'-bipiperidin-1 '-yl)-1 -[3-(trifluoromethvl)phenvl]-2-oxoethvl)cyclohexanol was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and N-(4-piperidine)piperidine. [0179] In an analogous manner to Example 1, step 2 1 -(2-(1,4'-bipiperidin-1 '-yl)-1 -f3-(trifluoromethyl)phenyllethyl)cvclohexanol dihydrochloride was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid. m/z 439 ([M+H]+); HRMS: calcd for C25H37F3N2O • 2.00 HCI, 510.2392; found (ESI), 439.2928. Example 21: 1-f1-(1-naphthvl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0180] In an analogous manner to Example 1, step 1 tert-butyl 4-[(1- hvdroxvcvclohexyl](1-naphthvl)acetvl1piperazine-1-carboxylate was prepared from (1-hydroxycyclohexyl)(1-naphthyl)acetic acid (Reference Example 1-e) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 453 ([M+H]+); HRMS: calcd for C27H36N2O4, 452.2675; found (ESI_FT), 453.27518. [0181] In an analogous manner to Example 1, step 2 1-M-(1-naphthyl)-2-piperazin-1-vlethvllcyclohexanol 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. 78 WO 2005/037809 PCT/US2004/033990 Example 22: 1-[2-(1,4'-bipiperidin-1l-yl)-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride [0182] In an analogous manner to Example 1, step 1 1-[2-(1.4'-bipiperidin-1'-vl)-1-(2-naphthvl)-2-oxoethvllcvclohoxanol was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and N-(4-piperidine)piperidine. [0183] In an analogous manner to Example 1, step 2 1-[2-(1,4'-bipiperidin-1'-yl)-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from 1-[2-(1,4'-bipiperidin-1'-yl)-1-(2-naphthyl)-2-oxoethyl]cyclohexanol. MS m/z 421 ([M+H]+); HRMS: calcd for C28H;oN20 ' 2.00 HCI, 492.2674; found (ESI), 421.3224. Example 23: 1 -{2-piperazin-1 -yl-1 -[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride [0184] In an analogous manner to Example 1, step 1 /erf-butyl 4-((1- hvdroxvcvclohexvl)[3-(trifluoromethoxv)phenvllacetvl)piperazine-1-caiboxylate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C24H33F3N2O5l 486.2342; found (ESI), 487.2398. [0185] In an analogous manner to Example 1, step 2 1 -(2-piperazin-1 -yl-1 -[3-(trifluoromethoxv)phenvliethyl]cyclohexanol dihydrochloride was prepared from terf-butyl 79 WO 2005/037809 PCT/US2004/033990 4-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acctyl}piperazine-1-carboxylate. HRMS: calcd for C19H27F3N2O2 2.00 HCI, 444.1558; found (ESI), 373.2095. Example 24: 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride [0186] 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 yield 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 precipitate was filtered and washed with diethyl ether to yield 299 mg (57%) 1-{2-(4-methylpiperazin-1 -yl)-1 -[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride as a white solid. HRMS: calcd for C20H29F3N2O2 • 2.00 HCI, 458.1715; found (ESI), 387.2263. Example 25: 1-[2-(4-aminopiperidin-1-yl)-1-(3-bromo-4-methoxyphenyl)ethyl]cyclohexanol dihydrochloride 80 WO 2005/037809 PCT/US2004/033990 [0187] In an analogous manner to Example 1, step 1 fe/t-butyl (1-[(3-bromo-4-methoxvphenvl)(1-hvdroxvcvclohexvl)acetyllpiperidin-4-vl|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. [0188] In an analogous manner to Example 13, step 2 fe/t-butyl {1-[2-(3-bromo-4-methoxypheiiyl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate was prepared from te/t-butyl {1-[(3-bromo-4-methaxyphenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS (ES) m/z 511.4 ([M+H]+); HRMS: caicd for C25H39BrN2O4) 510.2093; found (ESI), 511.2147. [0189] In an analogous manner to Example 14, 1-[2-(4-aminopiperidin-1-yI)-1-(3-bromo-4-methoxyphenyi)ethyl]cyclohexanol dihydrochloride was prepared from tert-' butyl {1 -[2-(3-bromophenyl)-2-(1 -hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate. MS m/z411/413 ([M+H]+); HRMS: calcd for C2oH3iBrN202 " 2.00 HCI, 482.1102; found (ESI), 411.1656. Example 26: 1-{2-(4-pyrrolidin-1-ylpiperidin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride [0190] In an analogous manner to Example 1, step 1 1 -(2-(4-pyrrolidin-1 -vlpiperidin-1 -yl]-1-[3-(trifluoromethvl)phenyl]-2-oxoethyl)cvclohexanol was prepared from (1- 81 WO 2005/037809 PCT/US2004/033990 hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetic acid (Reference Example 1-m) and 4-(1-pyrrolidinyl)piperidine. [0191] In an analogous manner to Example 1, step 2 i-{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)phenylJ-2-oxoethyl}cyclohexanol. MS m/z 425 ([M+H]+); HRMS: calcd for C«H35F3N2O 2.00 HCI, 496.2235; found (ESI), 425.2789. Example 27: 1-{1-[4-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride [0192] In an analogous manner to Example 1, step 1 tert-butyl 4-ff4- (benzvloxv)phenvl1(1-hvdroxvcvclohexvl)acetyl]piperazine-1-carboxylate was prepared from (4-benzyloxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-n) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 509 ([M+H]"); HRMS: calcd for C30H40N2O5, 508.2937; found (ESI), 509.3027. [0193] In an analogous manner to Example 1, step 1-{1-[4-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride was prepared from /erf-butyl 4-[[4-(benzyloxy)phenyl](1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C25H34N2O2 • 2.00 HCI, 466.2154; found (ESI), 395.2683. 1 Example 28:1 -{2-piperazin-1 -yl-1 -[4-(trifIuoromethoxy)phcnyl]ethyl}cyclohexanol dihydrochloride 82 WO 2005/037809 PCT/US2004/033990 [0194] In an analogous manner to Example 1, step 1 rert-butyl 4-U1- hvdroxvcvclohexvl)r4-(trifluoromethoxv)phenvllacetvl}pipera2ine-1-carboxvlate was prepared from (1-hydroxycyclohexyl)[4-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-g) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z487 ([M+H]+). [0195] In an analogous manner to Example 1, step 2 1-{2-piperazin-1-yl-1-[4-(trifluoromethoxy)phGnyl]ethyl}cyclohexanol dihydrochloride was prepared from tert-butyl 4-{(1-hydroxycyclohexyl)[4-(trifluoromethoxy)phenyl]acetyl}piperazine-1-carboxylato. MS m/z 373 ([M+H]+); Anal. Calcd for C1SH27F3N2O2 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 [0196] In an analogous manner to Example 1, step 1 tert-butyl (1-f(3-bromo-4-methoxyphenylH1-hvdroxvcyclohexvl)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-fH]+); HRMS: calcd for CasHayBrNaOs, 524.1886; found (ESI), 525.1971. [0197] In an analogous manner to Example 13, step 2 1-{1-(3-bromo-4- methoxyphenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride was prepared from tert-butyl {1-[(3-bromo-4-methoxyphenyl)(1- 83 WO 2005/037809 PCT/US2004/033990 hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS (ESI) m/z 425 ([M+H]+); HRMS: calcd fo"rib2iH33BrN202' 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 [0198] In an analogous manner to Example 1, step 1 fe/t-butyl (1-((1- hvdroxvcvc]ohexvl)r3-(trifluoromethvl)phenvllacetyl)piperidin-4-vl)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 C25H35F3N264, 484.2549; found (ESI), 485.2612. [0199] 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 frorr te/f-butyl (1 -{(1 -hydroxycycIohexyl)[3-(trifluoromethyl)phenyl]acetyl}piperidin-4- yl)carbamate. MS m/z 385 ([M+Hf); HRMS: calcd for C2iH3iF3N2O • 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 [0200]. In an analogous manner to Example 1, step 1 1 -H -(2-naphthvl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -vl)-2-oxoethyl1cvclohexanol was prepared from (1-hydroxycyc!ohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and 4-(1-pyrroiidinyl)piperidine. 84 WO 2005/037809 PCT/US2004/033990 [0201] 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 [0202] In an analogous manner to Example 1, step 1 /erf-butyl (1-f(1- hvdroxvcyclohexyl)(2-naphthyl)acetyl1piperidin-4-vl)carbamate 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 C2BH38N2O4, 466.2832; found (ESI), 467.2902. [0203] In an analogous manner to Example 13, step 2 /ert-butyl (1-[2-(1- . hvdroxvcvclohexvl)-2-(2-naphthyl)ethyl]piperidin-4-vl)carbamate was prepared from tert-butyl {1-[(1-hydroxycyclohexyl)(2-naphthyl)acetyl]piperidin-4-yl}carbamate. MS (ES) m/z 453.4 ([M+H]+); HRMS: calcd for C28H40N2O3, 452.3039; found (ESI), 453.3095. [0204] In an analogous manner to Example 14, 1-[2-(4-aminopiperidin-1-yl)-1-(2-naphthyl)ethy!]cyclohexanol dihydrochloride was prepared from terf-butyl (1-[2-(1-hydroxycyclohexyl)-2-(2-naphthyl)Gthyl]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 85 WO 2005/037809 PCT/US2004/033990 [0205] In an analogous manner to Example 1, step 1 A/-(3-chlorobenzyl)-2-(1 - hvdroxvcvclohexvl)-2-(2-naphthyl)acetamicle was prepared from (1- hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and 3-chlorobenzylamine. MS (ESI) m/z 408/410 ([M+H]+). [0206] In an analogous manner to Example 1, step 2 1-[2-[(3-chlorobenzyl)amino]-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride was prepared from A/-(3-chlorobenzyl)-2-(1-hydroxycyclohexyl)-2-(2-naphthyl)acetamide. MS m/z 394/396 ([M+H]*); HRMS: calcd for C25H28CINO • HCI, 429.1626; found (ESI), 394.191. Example 34: 1-[1-(3-chlorophenyl)-2-pyrrolidin-1-ylethyl]cyc!ohexanol hydrochloride [0207] In an analogous manner to Example 1, step 1 1 -f 1 -(3-chlorophenvl)-2-oxo-2-pyrrolidin-1-ylothvlicyclohexanol was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and pyrrolidine. MS (ESI) m/z 322/324 ([M+H]+); HRMS: calcd for C18H24CINO2, 321.1496; found (ESI_FT), 322.15603. [0208] 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-y!ethyl]cyclohexanol. HRMS: calcd for C18H26CINO • HCI, 343.1470; found (ESLFT), 308.17736. 86 WO 2005/037809 PCT/US2004/033990 Example 35: 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3-chlorophenyl)elhyl]cyclohexanol dihydrochloride [0209] In an analogous manner to Example 1, step 1 terf-butyl (1-f(3-chlorophenyl)(1-hydroxvcvclohexvl)acetyl1piperidin-4-vl)carbaiTiate 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]1); HRMS: calcd for C24H35CIN2O4, 450.2285; found (ESI), 451.2353. [0210] 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}cyclohexanol dihydrochloride [0211] A solution of 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 87 WO 2005/037809 PCT/US2004/033990 magnesium sulfate and concentrated in vacuo. The resulting colorless oil was treated with methanolic hydrochloric acid and diethyl ether to yield 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 [0212] In an analogous manner to Example 1, step 1 tert-butyl 4-K3.4- dichlorophenvl)(4-hvdroxv-1-methylpiperidin-4-vl)acetyl]piporazine-1-carboxvlate was prepared from (3,4-dichlorophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-i) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C23H33CI2N3O4, 485.1848; found (ESI_FT), 486.19305. [0213] In an analogous manner to Example 1, step 2 4-[1-(3,4-dichlorophenyl)-2-piperazin-1-ylethyl]-1-mothylpiperidin-4-ol trihydrochloride was prepared from fe/t-butyl 4-[(3,4-dichlorophenyl)(4-hydroxy-1-methylpipcridin-4-yl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C18H27CI2N3O • 3.00 HCI. 479.0831; found (ESI_FT), 372.16065. Example 38: 1-[2-(benzylamino)-1-(3,4-dichlorophenyl)ethyl]cyclohexanol hydrochloride [0214] In an analogous manner to Example 1, step 1 A/-benzyl-2-(3,4-dichlorophenvO-2-(1-hvdroxvcvclohexvl)acetamide was prepared from 3,4-dichloro-alpha-(1- 88 WO 2005/037809 PCT/US2004/033990 hydroxycyclohexyl)benzeneacetic acid (Reference : Example 1-d) and benzylamine. HRMS: calcd for C21H23CI2NO2, 391.1106; found (ESI_FT), 392.11598. [0215] 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 A/-benzyl-2-(3,4-dichlorophenyl)-2-(1-hydroxycyclohexyl)acetamide. HRMS: calcd for C21H25CI2NO • HCI, 413.1080; found (ESI_FT), 378.13864. Example 39: 1 -{2-(4-aminopiperidin-1 -yl)-1 -[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride [0216] In an analogous manner to Example 1,' step 1 tert-butvl (1-((1- hydroxvcyclohexyl)[3-(trifluoromethvl)phenvl]acetyl)piperidin-4-vl)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 C25H35F3N2O4, 484.2549; found (ESI), 485.2612. [0217] In an analogous manner to Example 13, step 2 rert-butyl (1-(2-(1- hvdroxvcyclohexvl)-2-[3-(trifluoromethvl)phenynethyl)piperidin-4-vl)carbamate was prepared from te/?-butyl (1-{(1-hydroxycyclohexyl)[3- (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)carbamate. MS (ES) m/z 471.4 ([M+H]+); HRMS: calcd for C25H37F3N2O3, 470.2756; found (ESI), 471.2852. [0218] In an analogous manner to Example 14, 1-{2-(4-aminopiperidin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride was prepared from /erf-butyl (1-{2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethyl)phenyl]ethyl}piperidin-4-yl)carbamate. MS m/z 371 ([M+H]+); HRMS: calcd for C2oH29F3N20 • 2.00 HCI, 442.1766; found (ESI), 371.2309. 89 WO 2005/037809 PCT/US2004/033990 Example 40: 1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclobutanol hydrochloride [0219] In an analogous manner to Example 1, step 1 A/-benzyl-2-(3-bromophenyl)-2-(1 -hydroxvcyclobutyQacetamide was prepared from (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and benzylamine. HRMS: calcd. for C19H2oBrN02j 373.0677; found (ESI_FT), 374.07415. [0220] In an analogous manner to Example 1, step 2 1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclobutanol hydrochloride was prepared from A/-benzyl-2-(3-bromophenyl)-2-(1-hydroxycyclobutyl)acetamide. HRMS: calcd for Ci9H22BrNO • HCI, 395.0652; found (ESI_FT), 360.09546. Example 41:1-[2-(benzylamino)-1-(3-chlorophenyl)ethyl]cyclohexanol hydrochloride WO 2005/037809 PCT/US2004/033990 Exampte 40:1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclobutanol hydrochloride [0219] In an analogous manner to Example 1, step 1 A/-benzyl-2-(3-bromophenyl)-2-(1 -hydroxycyclobutyDacetamide was prepared from (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j),and benzylamine. HRMS: calcd for CigH2oBrN02! 373.0677; found (ESI_FT), 374.07415. [0220] In an analogous manner to Example 1, step 2 1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclobutanol hydrochloride was prepared from A/-benzyl-2-(3-bromophenyl)-2-(1-hydroxycyclobutyl)acetamide. HRMS: calcd for CigH22BrNO " HCI, 395.0652; found (ESI_FT), 360.09546. Example 41:1-[2-(benzylamino)-1-(3-chlorophenyl)ethyl]cyclohexanol hydrochloride WO 2005/037809 PCT/US2004/033990 Example 1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclobutanol hydrochloride [0219] In an analogous manner to Example 1, step 1 A/-benzyl-2-(3-bromophenyl)-2-(1 -hydroxycyclobutyQacetamide was prepared from (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and benzylamine. HRMS: calcd for C19H20B1NO2, 373.0677; found (ESI_FT), 374.07415. [0220] In an analogous manner to Example 1, step 2 1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclobutanol hydrochloride was prepared from A/-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 [0221] In an analogous manner to Example 1, step 1 A/-benzyl-2-(3-chlorophenyl)-2-(1 -hydroxycyclohexvOacetamide was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and benzylamine. HRMS: calcd for C21H24CINO2, 357.1496; found (ESI_FT), 358.15607. [0222] 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 2005/037809 PCT/US2004/033990 chlorophenyl)-2-(1-hydroxycyclohexyl)acetamide. HRMS: calcd for C21H2CCINO ¦ HCI, 379.1470; found (ESI_FT), 344.17761. Example 42: 1 -[2-(cyclohexylamino)-1 -(3,4-dichlorophenyl)ethyl]cyclohexanol hydrochloride [0223] In an analogous manner to Example 1, step 1 A/-cyclohexyl-2-(3.4- dichlorophenyl)-2-(1-hvdroxvcyclohexyl)acetarnide was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and cyclohexylamino. MS (ESI) m/z384/386/388 ([M+H]*). [0224] In an analogous manner to Example 1, step 2 1-[2-(cyclohexylamino)-1-(3,4- dichlorophenyl)ethyl]cyclohexanol hydrochloride was prepared from A/-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 [0225] In an analogous manner to Example 1, step 1 fort-butyl (1-[(1- hydroxvcvclobutvl)(1-naphthvl)acetvHpiperidin-4-vl)carbarnate was prepared from (1- 91 WO 2005/037809 PCT/US2004/033990 hydroxycyclobutyl)(1-naphthyl)acetic acid (Reference Example 1-o) and 4-N-boc-aminop'tperidine. MS (ES) m/z 439.3 ([M+H]+). [0226] In an analogous manner to Example 1, step 2 1-[2-(4-aminopiperidin-1-yl)-1-(1-naphthyl)ethyl]cyclobutanol dihydrochloride was prepared from /ert-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 [0227] In an analogous manner to Example 1, step 1 A/-benzyl-2-(3-bromophenyl)-2-(4-hydroxv-1-methylpiperidin-4-vl)acetamide was prepared from (3-bromophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-r) and benzylamine. HRMS: calcd for C2iH25BrN2O2, 416.1099; found (ESI_FT), 417.11652. [0228] In an analogous manner to Example 1, step 2 4-[2-(benzylamino)-1-(3-bromophenyl)ethyl]-1-methylpiperidin-4-ol dihydrochloride was prepared from A/-benzyl-2-(3-bromophenyl)-2-(4-hydroxy-1-methylpiperidin-4-yl)acetamide. HRMS: calcd for C2:H27BrN2O 2.00 HCI, 474.0840; found (ESI_FT), 403.13802. Example 45: 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclopentanol dihydrochloride 92 WO 2005/037809 PCT/US2004/033990 [0229] In an analogous manner to Example 1, step 1 tert-butyl 4-f(1- hvdroxvcvclopentvl)(1-naphthvl)acetyl]piperazine-1-carboxvlate 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 C2SH34N2O4, 438.2519; found (ESI), 439.2563. [0230] In an analogous manner to Example 1, step 2 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclopentanol dihydrochloride was prepared from tert-butyl 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 [0231] In an analogous manner to Example 1, step 1 tert-butyl 4-((1- hvdroxvcvclobutvl)r3-(trifluoromethoxv)phenyl]acetvl)piperazine-1-carboxylate was prepared from (1-hydroxycyclobutyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-k) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C22H29F3N2O5, 458.2029; found (ESI), 459.2118. [0232] In an analogous manner to Example 1, step 2 1 -{2-piperazin-1 -yl-1 -[3-(trifluoromethoxy)phenyl]ethyl}cyciobutanol dihydrochloride was prepared from tert-butyl 4-{(1-hydroxycyclobutyl)[3-(trifluoromethoxy)phenyl]acetyl}piporazinG-1-carboxylate. HRMS: calcd for C17H23F3N2O2 • 2.00 HCI, 416.1245; found (ESI), 345.1801. Example 47: 1-{2-[(4-fluorobenzyl)amino]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol hydrochloride 93 WO 2005/037809 PCT/US2004/033990 [0233] In an analogous manner to Example 1, step 1 A/-(4-fluorobenzyl)-2-n-hvdroxvcvclohexyl]-2-f3-(trifluoromethvl)phenyl]acetamide was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetic acid (Reference Example 1-m) and 4-fluorobenzylamine. MS (ESI) m/z 410 ([M+H]+). [0234] 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 C22H25F4NO • HCI, 431.1639; found (ESI), 396.1931. Example 48: 1-[1-(3-bromophenyl)-2-(cyclohexylamino)ethyl]cyclohexanol hydrochloride [0235] In an analogous manner to Example 1, step 1 2-(3-bromophenvO-A/-cvclohexyl-2-( 1 -hydroxycyclohexvOacetamide was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and cyclohexylamine. MS (ESI) m/z394/396 ([M+H]+). [0236] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2-(cyclohexylamino)ethyl]cyc!ohexanol hydrochloride was prepared from 2-(3-bromophenyl)-/V-cyclohexyl-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z 380/382 ([M+H]+); HRMS: calcd forCMH3oBrNO • HCI, 415.1278; found (ESI), 380.1574. 94 WO 2005/037809 PCT/US2004/033990 Example.49: 1-[2-[4-(methylamino)pjperidin-1-yl]-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride [0237] In an analogous manner to Example 1, stop 1 /erf-butyl (1-fd- hvdroxvcvclohexyl)(2-naphthvl)acGtyl]piperidin-4-vl)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+HD; HRMS: calcd for C28H38N2O4, 466.2832; found (ESI), 467.2902. [0238] In an analogous manner to Example 13, step 2 1-[2-[4-(methylamino)piperidin-1-yl]-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from /erf-butyl {1-[(1-hydroxycyclohexyl)(2-naphthyl)acetyl]piperidin-4-yl}carbamate. MS m/z 367 ([M+H]+); HRMS: calcd for C24H34N2O • 2.00 HCI, 438.2205; found (ESI), 367.2763. Example 50: 2-(3-bromophenyl)-3-ethyl-1-pipcrazin-1-ylpentan-3-ol dihydrochloride [0239] In an analogous manner to Example 1, step 1 fert-butyl 4-[2-(3-bromophenyl)-3-ethvl-3-hvdroxvpentanovl]piperazine-1-carboxylate was prepared from 2-(3-bromophenyl)-3-ethyl-3-hydroxypentanoic acid (Reference Example 1-t) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 469/471 ([M+H]+); HRMS: calcd for C22H33BrN2O4> 468.1624; found (ESI_FT), 469.17071. 95 WO 2005/037809 PCT/US2004/033990 [0240] In an analogous manner to Example 1, step 2 2-(3-bromophenyl)-3-ethyl-1-ptperazin-1-ylpentan-3-ol dihydrochloride was prepared from /erf-butyl 4-[2-(3-bromophenyl)-3-e;hyl-3-hydroxypentanoyl]piperazine-1-carboxylate. MS (ESI) m/z 355/357 ([M+H]+); HRMS: calcd for Ci7H27BrN2O 2.00 HCI, 426.0840; found (ESI_FT), 355.13878. Example 51: 4-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]heptan-4-ol dihydrochloride [0241] In an analogous manner to Example 1, step 1 te/t-butyl 4-[2-(3-chlorophenyl)-3-hvdioxv-3-propylhexanovl1piperazine-1-carboxvlate 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. [0242] In an analogous manner to Example 1, step 2 4-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]heptan-4-ol dihydrochloride was prepared from te/?-butyl 4-[2-(3-chlorophenyl)-3-hydroxy-3-propylhexanoyl]piperazino-1-carboxylate. MS (ESI) m/z 339/341 ([M+H]4); HRMS: calcd for C19H31CIN2O • 2.00 HCI, 410.1658; found (ESI_FT), 339.21916. Example 52: 2-(3-chlorophenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol dihydrochloride 96 WO 2005/037809 PCT/US2004/033990 [0243] Jn.an analogous manner to Example 1, step 1 tert-butvl 4-r2-(3-chlorophenyl)-3-ethvl-3-hvdroxypentanovHpiperazine-1-carboxvlate was prepared from 2-(3-chlorophenyl)-3-ethyl-3-hydroxypentanoic acid (Reference Example 1-v) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 425/427 ([M+H]+). [0244] 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 [0245] In an analogous manner to Example 1, step 1 tert-butyl 4-[2-(3-chlorophenyl)-3-Gthyl-3-hydroxypentanovl1piperazine-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. [0246] In an analogous manner to Example 1, step 2 3-ethyl-2-(1-naphthyl)-1-piperazin-1-ylpentan-3-ol dihydrochloride v^as prepared from fert-butyl 4-[2-(3-chlorophenyl)-3-ethyl-3-hydroxypentanoyl]piperazine-1-carboxylate. MS (ESI) m/z 327 ([M+H]"); HRMS: calcd forC2iH3oN20 • 2.00 HCI, 398.1892; found (ESI), 327.2426. Example 54: 1-[2-(4-aminopiperidin-1-yl)-1-(1-naphthyl)ethyl]cyclohexanol dihydrochlorido 97 WO 2005/037809 PCT/US2004/033990 [0247] In an analogous manner to Example 1, step 1 tert-butyl f1-f(1- hvdroxvcvclohexvl)f1-naphthyl)acetyl]piperidin-4-vl)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]+). [0248] In an analogous manner to Example 1, step 2 1-[2-(4-aminopiperidin-1-yl)-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from terf-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-(1,2,3,4-tetrahydronaphthalen-1 -ylamino)ethyl]cyclohexanol hydrochloride [0249] In an analogous manner to Example 1, step 1 2-(3-bromophenyl)-2-(1 -hydroxycyclohexvl)-A/-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/z442/444 ([M+H]+). r0250] In an analogous manner to Example 1, stop 2 1-[1-(3-bromophenyl)-2-(1,2,3,4-¦etrahydronaphthalen-1-ylamino)ethyl]cyclohexanol hydrochloride was prepared from 2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)-A/-1,2,3,4-tetrahydronaphthalen-1- 98 WO 2005/037809 PCT/US2004/033990 ylacetamide. MS (ESI) m/z 428/430 ([M+H]+); HRMS: calcd for C24H30B1-NO ¦ HCI, 463.1278; found (ESI), 428.1593. Example 56: 1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclopentanol dihydrochloride [0251] In an analogous manner to Example 1, step 1 1 -[2-(4-methylpiperazin-1 -yl)-1 -(i-naphthyl]-2-oxoethvllcvclopentanol was prepared from (1-hydroxycyclopentyl)(1-naphthyl)acetic acid (Reference Example 1-s) and A/-methylpiperazine. MS (ESI) m/z -353 ([M+H]+). [0252] 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 C22H3oN20 - 2.00 HCI, 410.1892; found (ESI), 339.2419. Example 57: 1-[1-(3-chlorophenyl)-2-morpholin-4-ylethyl]cyclohexanol hydrochloride [0253] In an analogous manner to Example 1, step 1 1 -[1 -(3-chlorophenyl)-2-morpholin-4-vl-2-oxoethvllcyclohexanol was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and morpholine. HRMS: calcd for Ci8H24CINO3, 337.1445; found (ESL.FT), 338.1521. 99 WO 2005/037809 PCT/US2004/033990 [0254] In an analogous manner to Example 1, step 2 1-[1-(3-chlorophenyl)-2-morpH^n-4-ylethyljcyclohexanol hydrochloride was prepared from 1-[1-(3-ch!orophenyl)-2-morphoIin-4-yl-2-oxoethyl]cycIohexanol. HRMS: calcd for Ci8H26CINO2 • HCI, 359.1419; found (ESLFT), 324.17137. Example 58: 4-[1 -(3-bromophenyl)-2-piperazin-1 -ylethyl]-1 -methy!piperidin-4-ol dihydrochloride [0255] In an analogous manner to Example 1, step 1 fert-butyl 4-r(3-bromophenyl)(4-hvdroxv-1-methvlpiperidin-4-vl)acetyl]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 (ESI_FT), 496.18082. [0256] 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 te/t-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. Example 59: 1 -methyl-4-[1 -(2-naphthyl)-2-piperazin-1 -ylethyl]piperidin-4-ol dihydrochloride [0257] In an analogous manner to Example 1, step 1 ferf-butyl 4-[(4-hydroxy-1-methvlpiperidin-4-vl)(2-naphthvl)acetvi]piperazine-1-carboxvlate was prepared from (4- 100 WO 2005/037809 PCT/US2004/033990 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 (ESI_FT), 468.28561. [0258] 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 tetf-butyl 4-[(4-hydroxy-1 -methylpiperidin-4-yl)(2-naphthyl)acetyl]piperazine-1 -carboxylate. HRMS: calcd for C22H31N3O • 3.00 HCI, 461.1767; found (ESl_FT), 354:25401. Example 60: 1 -{1 -(3-bromophenyl)-2-[(3-chlorobenzyl)amino]ethyl}cyclohexanoI hydrochloride [0259] In an analogous manner to Example 1, step 1 2-(3-bromophenvO-/V-(3-chlorobenzyl)-2-(1-hvdroxycyclohexvl)acetamide was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 3-chlorobenzylamine. MS (ESI) m/z436/438/440 ([M+H]+). [0260] In an analogous manner to Example 1, step 2 1-{1-(3-bromophenyl)-2-[(3-ch!orobenzyl)amino]ethyl}cyclohexanol hydrochloride was prepared from 2-(3-bromophenyl)-A/-(3-chlorobenzyl)-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z 422/424/426 ([M+H]+); HRMS: calcd for C2iH25BrCINO • HCI, 457.0575; found (ESI), 422.0873. 101 Example 61: 1-[2-(benzylamino)-1-(3-bromophenyl)ethyl]cyclohexanol hydrochloride WO 2005/037809 PCT/US2004/033990 '[0261] ' in an analogous manner to Example 1, step 1 A/-benzyl-2-(3-bromophenyl)-2-(1 -hydroxvcvclohexyl)acetamide was prepared from (3-bromophenyl)(1-:hydroxycyclohexy!)acetic acid (Reference Example 1-b) and benzylamine. HRMS: calcd for C21H24BrNO2, 401.0990; found (ESI_FT), 402.10557. [0262] In an analogous manner to Example 1, step 2 1-[2-(benzy!amino)-1-(3-bromophenyl)ethyl]cyclohexanol hydrochloride was prepared from A/-benzyl-2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)acetamide. HRMS: calcd for C2iH26BrNO • HCI, 423.0965; found (ESI_FT), 388.12785. Example 62:1-[2-(benzylamino)-1-(2~naphthyl)ethyl]cyclohexanol hydrochloride [0263] In an analogous manner to Example 1, step 1 A/-benzyl-2-(1- hvdroxvcvclohexyl)-2-(2-naphthvl)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. [0264] In an analogous manner to Example 1, step 2 1-[2-(benzylamino)-1-(2-naphthyl)e_thyl]cyclohexanol hydrpchloride was prepared from A/-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-y!ethyl]cyclohexanol dihydrochloride 102WO 2005/037800 PCT/US2004/033990 [0265] In an analogous manner to Example 1, step 1 ferf-butyl 4(1- hvdroxvcvclohexyl](2-naphthvl)acetvllpiperazine-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]+). [0266] In an analogous manner to Example 1, step 2 1-[1-(2-naphthy))-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from /erf-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 [0267] 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 (sec Example 63). MS (ESI) m/z 353 ([M+H]+); HRMS: calcd for C23H32N2O • 2.00 HCI, 424.2048; found (ESl_FT), 353.25994. Example 65: 2-(3-bromo-4-methoxyphenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol dihydrochloride [0268] In an analogous manner to Example 1, step 1 ferf-butyl 4-[2-(3-bromo-4-methoxvphenvO-3-ethvl-3-hvdroxypentanoyl]piperazine-1-carboxvlate was prepared from 2-(3-bromo-4-methoxyphenyl)-3-ethyl-3-hydroxypentanoic acid (Reference 103 WO 2005/037809 PCT/US2004/033990 Example 1-y) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 499/501 ([M+H]+); HRMSrtalcd for C23H35BrN2O5, 498.1729; found (ESI), 499.1793. [0269] 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 C18H2oBrN202 • 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 [0270] 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 '0271] In an analogous manner to Example 1, step 1 2-(3-chlorophenvl)-A/-cvclohexyl-2-(1-hvdroxvcvclohexyl)acetamide was prepared from (3-chlorophenyl)(1- 104 WO 2005/037800 PCT/US2004/033990 hydro>;ycyclohexyl)acetic acid (Reference Example 1-a) and cyclohexylamine. MS (ESI) m/z 350/352 ([M+H]+). [0272] In an analogous manner to Example 1, step 2 1-[1-(3-chlorophenyl)-2-(cyclohexylamino)ethyl]cyc!ohexanol hydrochloride was prepared from 2-(3-chlorophenyl)-A/-cyclohexyl-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z 336/338 ([M+H]+); HRMS: calcd for C20H3cCINO • HCI, 371.1783; found (ESI), 336.206. Example 68: 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclobutanol dihydrochloride [0273] In an analogous manner to Example 1, step 1 fert-butyl 4-fd- hvdroxvcvclobutvl)(1-naphthyl)acetvllpiperazine-1-carboxvlate was prepared from (1-hydroxycyclobutyl)(1-naphthyl)acetic acid (Reference Example 1-o) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z425 ([M+H]+). [0274] In an analogous manner to Example 1, step 2 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclobutanol dihydrochloride was prepared from /erf-butyl 4-[(1-hydroxycyclobutyl)(1-naphthyl)acetyl]piperazine-1-carboxylato. MS (ESI) m/z 311 ([M+H]*); HRMS: calcd for C20H26N2O • 2.00 HCI, 382.1579; found (ESI), 311.2127. Example 69: 1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclobutanol dihydrochloride 105 WO 2005/037809 PCT/US2004/033990 [0275] In an analogous manner to Example 24, 1-[2-(4-methylpiperazin-1-yl)-1-(1-naphtli^!)ethyl]cyclobutanol dihydrochloride was prepared from 1-[i-(1-naphthyl)-2-piperazin-1-y)eihy)]cyclobutanol (see Example 68). MS (ES) m/z 325.3 ((M+H]+); HRMS: calcd for C2iH28N2O ¦ 2.00 HCI, 396.1735; found (ESI), 325.2278. Example 70: 1-{1-[4-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol dihydrochloride [0276] In an analogous manner to Example 1, step 1 /erf-butyl 4-[[4- (benzvloxv)phenvl1(1-hvdroxvcvclobutyl)acetyl]piperazine-1-carboxvlate 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 CaaHaeNsOs, 480.2624; found (ESI), 481.2716. [0277] In an analogous manner to Example 1, step 2 1-{1-[4-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyc!obutanol dihydrochloride was prepared from /erf-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 mr. WO 2005/037S09 PCT/US2004/033990 [0278] 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 [0279] In an analogous manner to Example 1, step 1 te/t-butyl 4-[1-(3-chlorophenvlphenvl)(1-hvdroxvdecahvdronapthvl)acetyl1piperazine-1-carboxvlate was prepared from (3-chlorophenyl)(1-hydroxydecahydronapthyl)acetic acid (Reference Example 1-aa) and terf-butyl 1-piperazinecarboxylate. MS (ESI) m/z491/493 ([M+H]+). [0280] In an analogous manner to Example 1, step 2 1-[1-(3-chlorophenyl)-2- piperazin-1-y]ethyl]decahydronaphthalen-1-ol dihydrochloride was prepared from tert- butyl 4-[1-(3-chlorophenylphenyl)(1-hydroxydecahydronapthyl)acetyl]piperazine-1- carboxylate. MS (ES) m/z 377.3 ([M+H]4); HRMS: calcd for C2?H33CIN2O • 2.00 HCI, 448.1815; found (ESI), 377.2351. Example 73: 1-[1-(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazin-1-yl)ethyl]-4-terf-butylcyclohexanol dihydrochloride 107 WO 2005/037809 PCT/US2004/033990 [0281] In an analogous manner to Example 1, step 1 1-M-(3-bromo-4-methoxyphenvl)-2-(4-methvlpiperazin-1-vl)-2-oxoethyl]-4-tert-butylcvclohexanol was prepared from (3-bromo-4-methoxyphenyl)(4-/£?rt-butyl-1 -hydroxycyclohexyl)acetic acid (Reference Example 1-bb) and A/-methylpiperazine. MS (ESI) m/z 481/483 ([M+H]+). [0282] In an analogous manner to Example 1, step 2 1-[1-(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazin-1-yl)ethyl]-4-terf-butylcyclohexanol dihydrochloride was prepared from /erf-butyl 1 -[1 -(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazin-1 -yl)-2-oxoethyl]-4-terf-butylcyclohexanol. MS (ESI) m/z 467/469 ([M+H]+); HRMS: calcd for Ca^BrlNbC^ ¦ 2.00 HCI, 538.1728; found (ESI), 467.2258. Example 74: 2-[1 -(3-chlorophenyl)-2-piperazin-1 -ylethyl]decahydronaphthalen-2-ol dihydrochloride [0283] In an analogous manner to Example 1, step 1 fert-butyl 4-f1-(3-chlorophenvlphenyl)(2-hydroxvdecahydronapthvl)acetyl]piperazine-1-carboxylate was prepared from (3-chlorophenyl)(2-hydroxydccahydronapthyl)acetic acid (Reference Example 1-cc) and /erf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 491/493 ([M+H]+). [0284] In an analogous manner to Example 1, step 2 2-[1-(3-chlorophenyl)-2- piperazin-1-ylethyl]dccahydronaphthalen-2-ol dihydrochloride was prepared from tert- butyl 4-[1 -(3-chlorophenylphenyl)(2-hydroxydecahydronapthyl)acetyl]piperazine-1 - ios WO 2005/037809 PCT/US2004/033990 caiboxylats. MS (ESI) m/z 377 ([M+H]*); HRMS: calcd for C22H33CIN2O • 2.00 HCI, 448.1815; found (ESI), 377.2346. Example 75: 1-(1-(3,4-dichlorophenyl)-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride [0285] In an analogous manner to Example 1, step 1 2-(3.4-dichlorophenyl)-2-( 1 -hvdroxvcyclohexyl)-A/-f4-(trifluoromethvl)benzvl1acGtamide was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and 4-trifluoromethylbenzylamine. MS (ESI) m/z 460/462/464 ([M+H]+). [0286] In an analogous manner to Example 1, step 2 1-(1-(3,4-dichlorophenyl)-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)cyclohexano! hydrochloride was prepared from 2-(3,4-dichlorophenyl)-2-(1-hydroxycyclohexyl)-A/-[4-(trifluoromethyl)benzyl]acetamide. MS (ESI) m/z 446/448/450 ([M+H]+); HRMS: calcd for CaaHaaClaFaNO • HCI, 481.0954; found (ESI), 446.1232; Anal. Calcd for C22H24CI2F3NO • HCI: C, 54.73; H, 5.22; N, 2.90. Found: C, 54.69; H, 4.99; N, 2.78. Example 76: 4-ferr-buryl-1-[1-(1-naphthyl)-2-pipcrazin-1-ylethyl]cyclohexanol . dihydrochloride [0287] In an analogous manner to Example 1, step 1 tert-butyl 4-[(4-fert-butyl-1-hvdroxvcvclohexyl)(1-naphthyl)acetyllpiperazine-1-carboxvlate was prepared from (4- 109 WO 2005/037809 PCT/US2004/033990 tert-butvl-1-hydroxycyclohexyl)(1-naphthyl)acetic acid (Reference Example 1-dd) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 509 ([M+H]+); HRMS: calcd for C3iH44N2O<, 508.3301; found (ESI), 509.3354. [0288J In an analogous manner to Example 1, step 2 4-te/?-butyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from fert-butyl 4-[(4-tert-butyl-1-hydroxycyclohexyl)(1-naphthyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 395 ([M+H]+); HRMS: calcd for C26H30N2O ¦ 2.00 HCI, 466.2518; found (ESI), 395.3055. Example 77: 4-[1 -(3-chlorophenyl)-2-piperazin-1 -ylethyl]tetrahydro-2H-pyran-4-ol dihydrochloride |0289] In an analogous manner to Example 1, step 1 fe/t-butyl 4-f(3-chlorophenyl)(4-hvdroxvtetrahydro-2H-pvran-4-vl)acetvllpiperazine-1-carboxylate was prepared from (3-chlorophenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetic acid (Reference Example 1-ee) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z439/441 ([M+H]*); HRMS: calcd for C22H31CIN2O5, 438.1921; found (ESI_FT), 439.19884. [0290] 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-hydroxytetrahydro-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-2fy-pyran-4-ol dihydrochloride no WO 2005/037809 PCT/US2004/033990 [0291] In an analogous manner to Example 24, 4-[1-(3-chlorophenyl)-2-(4- methylpiperazin-1-yl)ethyl]tetrahydro-2/-/-pyran-4-ol dihydrochloride was prepared from 4-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]tetrahydro-2/-/-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)ethyi]-4-terf-butylcyclohexanol dihydrochloride [0292] In an analogous manner to Example 1, step 1 1 -f 1 -(3-bromophenyl)-2-(4-methvlpipera7_in-1-vO-2-oxoethvl1-4-tert-butylcyclohexanol was prepared from (3-bromophenyl)(4-tert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-ff) and A/-methylpipcrazine. MS (ESI) m/z451/453 ([M+H]+). [0293] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]-4-fcrt-butylcyclohexanol dihydrochloride was prepared from 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)-2-oxoethyl]-4-/ert-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 in WO 2005/037809 PCT/US2004/033990 [0294] In an analogous manner to Example 1, step 1 2-(3,4-dichlorophenvl)-A/-(4-fluorobenzvl)-2-(1-hvdroxvcvclohexyl)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]+). [0295] 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)-/V-(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 [0296] In an analogous manner to Example 1, step 1 te/t-butyl 4-[2-(3-bromophenvO-3-hydroxy-3-propylhexanoyl]piperazine-1 -carboxylate was prepared from 2-(3-bromophenyl)-3-hydroxy-3-propylhexanoicacid (Reference Example 1-gg) and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 497.2 ([M+H]+). [0297] In an analogous manner to Example 1, step 2 4-[1-(3-bromophenyl)-2-piperazin-1-y!ethyl]heptan-4-ol dihydrochloride was prepared from te/t-butyl 4-[2-(3-bromophenyl)-3-hydroxy-3-propylhexanoy!]piperazine-1 -carboxylate. MS (ES) m/z 383.2 ([M+H]+); HRMS: calcd forC19H31BrN2O • 2.00 HCI, 454.1153; found (ESI), 383.1705. 112 WO 2005/037809 PCT/US2004/033990 Example 82: 4-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yI)ethyl]heptan-4-ol dihydrochloride [0298] 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 [0299] In an analogous manner to Example 1, step 1 1 -[1 -(3,4-dichlorophenyl)-2-morpholin-4-vl-2-oxoethyl]cyclobutanol was prepared from (3,4-dichlorophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-p) and morpholine. HRMS: calcd for C16H19CI2NO3) 343.0742; found (ESI_FT), 344.08102. [0300] In an analogous manner to Example 1, step 2 1-[1-(3,4-dichlorophenyl)-2- morpholin-4-ylethyl]cyc!obutanol hydrochloride was prepared from 1-[1-(3,4- dichlorophenyl)-2-morpholin-4-yl-2-oxoethyi]cyclobutanol. HRMS: calcd for C16H21CI2NO2 " HCI, 365.0716; found (ESI_FT), 330.10064. 113 WO 2005/037809 PCT/US2004/033990 Example.84:1 -[1 -(3-bromo-4-methoxyphenyl)-2-piperazin-1 -ylethyl]-4-tert-butylcyclofiexanol dihydrochloride [0301] In an analogous manner to Example 1, step 1 tert-butyl 4-[(3-bromo-4-methoxyphenvl)(4-tert-butvl-1 -hvdroxvcvclohexvl)acetyl1piperazine-1 -carboxvlate was prepared from (3-bromo-4-methoxyphenyi)(4-tert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-bb) and terf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 567/569 ([M+H]4); HRMS: calcd for C28HBrN2O5, 566.2355; found (ESI), 567.2435. [0302] In an analogous manner to Example 1, step 2 1-[1-(3-bromo-4-methoxyphenyl)-2-piperazin-1-ylethyl]-4-tert-butylcyclohexanol dihydrochloride was prepared from tert-butyl 4-[(3-bromo-4-methoxyphenyl)(4-tert-butyl-1-hydroxycycIohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 453/455 ([M+H]4); 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 [0303] In an analogous manner to Example 1, step 1 1 -[1 -(3-chlorophenyl)-2-oxo-2-piperidin-1-ylethvlicyclohexanol was prepared from (3-chlorophenyl)(1-hydrdxycyclohexyl)acetic acid (Reference Example 1-a) and piperidine. HRMS: calcd for C19H26CINO2, 335.1652; found (ESI_FT), 336.17194. [0304] In an analogous manner to Example 1, step 2 1-[i-(3-chlorophenyl)-2-piperidin-1-ylethyl]cyclohexanol hydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-oxo-2- 114 WO 2005/037809 PCT/US2004/033990 pipeririin-1-ylethyl]cyclohexanol. HRMS: calcd for C19H28CINO • HCI, 357.1626; found (ESLFT), 322.19304. Example 86: 2-(3-chlorophenyl)-1,1-dicyclopropyl-3-(4-methylpiperazin-1-yl)propan-1-ol dihydrochloride [0305] In an analogous manner to Example 1, step 1 ferf-butyl 4-r2-(3-chlorophenyl) (3,3-dicvclopropvl-3-hvdroxvpropvl)acetyl1piperazine-1-carboxvlate was prepared from 2-(3-chlorophenyl)-3,3-dicyclopropyl-3-hydroxypropanoic acid (Reference Example 1-hh) and /V-methylpiperazine. MS (ESI) m/z363 ([M+H]+). [0306] 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 fert-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 C20H29CIN2O ¦ 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 ' [0307] In an analogous manner to Example 1, step 1 fe/f-butyl 4-r(3-bromophenvl)(1-hvdroxv-3,3,5,5-tetramethvlcyclohexvl)acetyl]piperazine-1-carboxvlate was prepared 115 WO 2005/037809 PCT/US2004/033990 from (3.-bromophenyl)(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetic acid (Reference Example 1-ii) and tert-butyl 1-piperazinecarboxylate. [0308] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-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)acetyl]piperazine-1-carboxylate. MS (ES) m/z 423.2 ([M+H]+); HRMS: calcd for C22H35BrN2O1 422.1933; found (ESI), 423.2015. Example 88: 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]-3,3,5,5-tetramethylcyclohexanol dihydrochloride [0309] In an analogous manner to Example 24, 1-[1-(3-bromophenyl)-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- tetramethylcyclohexanol (see Example 87). MS (ES) m/z 437.3 ([M+Hf); 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 [0310] 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- WO 2005/037809 PCT/US2004/033990 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-(1-(3-bromophenyl)-2-{[4-"(trifluoromethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride [0311] In an analogous manner to Example 1, step 1 2-(3-bromophenyl)-2-(1 -hvdroxvcvclohexvl)-N-[4-(trifluoromethyl)benzyl]acetamide was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-trifluoromethylbenzylamine. MS (ESI) m/z470/472 ([M+H]+). [0312] In an analogous manner to Example 1, step 2 T-(1-(3-bromophenyl)-2-{[4- (trifluoromethyl)benzyl]amino}ethyl)cyc!ohexano! hydrochloride was prepared from 2-(3- bromophenyl)-2-(1-hydroxycyclohexyl)-A/-[4-(trifluoromethyl)benzyl]acetamide. MS (ESI) m/z 456/458 ([M+H]+); HRMS: calcd for C22H25BrF3NO • HCI, 491.0838; found (ESI), 456.1147. Example 91: 4-ethyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride 117 WO 2005/037809 PCT/US2004I/033990 [0313] In an analogous manner to Example 1, step 1 /erf-butyl 4-ri-(1-naphthyl)- (4-ethvl-1-hvdroxvcvclohexvl)acetvl1piperazine-1-carboxylate was prepared from (4-ethyl-1-hydroxycyclohexyl) -(1-naphthyl) acetic acid (Reference Example 1-jj) and /erf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 481 ([M+Hf); [0314] In an analogous manner to Example 1, step 2 4-ethyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from /erf-butyl 4-[1-(1-naphthyl)- (4-ethyl-1-hydroxycyclohexyl)acetyl]piperazine-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 [0315] 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 C18H25F3N2O2' 2.00 HCI, 430.1402; found (ESI), 359.1965. i Example 93: 4-ferf-butyl-1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride l is WO 2005/037809 PCT/US2004/03399O [0316] In an analogous manner to Example 1, step 1 tert-butyl 4-f(4-/ert-butyl-1-hvdroxvcvclohexvl)(3-chlorophenyl)acetyl]piperazine-1-carboxvlate was prepared from (3-chlorophenyl)(4-/ert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-kk) and /erf-butyl 1-piperazinecarboxylate. MS (ES) m/z 493.4 ([M+H]*). [0317] In an analogous manner to Example 1, step 2 4-te/t-butyl-1-[1-(3-chlorophenyl)- 2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from terf-butyl 4-[(4- fer/-butyl-1-hydroxycyclohexyl)(3-chlorophenyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 379 ([M+H]+); HRMS: calcd for C^HasCIN^O, 378.2438; found (ESI), 379.2513. Example 94:2-(3-chlorophenyl)-3-ethyl-1 -(4-methylpiperazin-1 -yl)pentan-3-ol dihydrochloride [0318] In an analogous manner to Example 24, 2-(3-chlorophenyl)-3-ethyl-1-(4-methylpiperazin-1-yl)pentan-3-ol dihydrochloride was prepared from 2-(3-chlorophenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol (see Example 52). (ESI) m/z 325/327 ([M+H]+); HRMS: calcd for C18HsSCIN2O • 2.00 HCI, 396.1502; found (ESI), 325.2032. Example 95:1-[1-(3-bromophenyl)-2-morpholin-4-ylethyl]cyclobutanol hydrochloride 119 WO 2005/037809 PCT/US2004/033990 [0319] In an analogous manner to Example 1, step 1 1 -f 1 -(3-bromophenvl)-2-morpholin-4-vl-2-oxoethvllcvclobutanol was prepared from (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and morpholine. HRMS: calcd for C16H23BrNO3, 353.0627; found (ESI._FT), 354.06919. [0320] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2- morpholin-4-ylethyl]cyclobutanol hydrochloride was prepared from to/t-butyl 4-[(4-/erf- butyl-1-hydroxycyclohexyl)(3-chlorophenyl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C16H22BrNO2 HCI, 375.0601; found (ESI_FT), 340.08898. Example 96: 1-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]-4-/erf-butylcyclohexanol dihydrochloride [0321] In an analogous manner to Example 1, step 1 /erf-butyl 4-[(3-bromophenyl)(4-/ert-butyl-1-hydroxycvclohexvl)acetyl]piperazine-1-carboxylate was prepared from (3-bromophenyl)(4-te/?-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-ff) and ferf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 537/539 ([M+H]+); HRMS: calcd for C27H4iBrN2O,., 536.2250; ^ound (ESI), 537.2324. [0322] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2- piperazin-1-ylethyl]-4-ferf-butylcyclohexanoi dihydrochloride was prepared from tert- butyl 4-[(3-bromophenyl)(4-ferf-butyl-1-hydroxycyclohexyl)acetyl]piperazine-1- 120 WO 2005/037809 PCT/US2004/033990 carboxylate. MS (ESI) m/z 423/425 ([M+H]+); HRMS: calcd for C^sBrNaO • 2.00 HCI, 494.1466; found (ESI), 423.1994. Example 97: 4-methyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0323] In an analogous manner to Example 1, step 1 tert-butyl 4-f1-(1-naphthyl)- (4-methvl-i-hydroxycvclohexyDacetvllpiperazine-i-carboxvlate was prepared from (4-methyl-1-hydroxycyclohexyl) -(1-naphthyl) acetic acid (Reference Example 1-11) and terf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 467 ([M+H]+). [0324] 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 [0325] In an analogous manner to Example 1, step 1 2-(3-bromophenyl)-A/-(4- fluorobenzyl)-2-( 1 -hydroxycyclohexvOacetamide was prepared from (3-bromophenyl)(1- 121 WO 2005/037809 PCT/US 2004/033990 hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-fluorobenzylamine. MS (ESI) m/z420/422 ([M+H]'). [0326] 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)-A/-(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 [0327] In an analogous manner to Example 1, step 1 1 -f. 1 -(3-bromophenyl)-2-morpholin-4-vl-2-oxoethyl]cyclohexanol was prepared.from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and morpholine. HRMS: calcd for Ci8H24BrNO3, 381.0940; found (ESI_FT), 382.10032. [0328] In an analogous manner to Example 1, step 2 1-[1-(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 CieH26BrNO2 HCI, 403.0914; found (ESI_FT), 368.12137. Example 100: 4-fert-butyl-1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride 122 WO 2005/037809 PCT/US2004/033990 [0329] In an analogous manner to Example 24, 4-fe/Tf-butyl-1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from 4-fert-butyl-1-[1-(1-naphthy!)-2-piperazin-1-ylethyl]cyclohexanol (see Example 76). MS (ESI) m/z 409 ([M+H]+); HRMS: calcd for C27H4oN20 • 2.00 HCI, 480.2674; found (ESI), 409.3207. Example 101: 4-tert-butyI-1 -[1 -(3-chloropheny!)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride [0330] In an analogous manner to Example 24, 4-fert-butyl-1-[1-(3-chlorophenyl)-2-(4-methylpiperazin-1-yl)ethy!]cyclohexanol dihydrochloride was prepared from 4-ferf-butyl-1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 93). MS (ESI) m/z 393 ([M+H]4); HRMS: calcd for C23H37CIN2O • 2.00 HCI, 464.2128; found (ESI), 393.2673. Example 102: 1 -methyl-4-[2-morphoiin-4-yl-1 -(2-naphthyl)ethyl]piperidin-4-ol hydrochloride 123 WO 2005/037809 PCT/US2004/033990 [0331] In an analogous manner to Example 1, step 1 1 -methvl-4-[2-morpholin-4-yl-1 -(2-naphthvl)-2-oxoethyllpiperidin-4-ol was prepared from (4-hydroxy-1-methylpiperidin-4-yl)(2-naphthyl)acetic acid (Reference Example 1-x) and morpholine HRMS: calcd for C??H28N2O3, 368.2100; found (ESI_FT)t 369.21652. [0332] In an analogous manner to Example 1, step 2 1-methyl-4-[2-morpholin-4-yl-1-(2-naphthyl)ethyl]piperidin-4-ol hydrochloride was prepared from 1-methyl-4-[2-morpholin-4-y!-1-(2-naphthyl)-2-oxoethyl]p:peridin-4-ol. HRMS: calcd for C22H30N2O2 ' 2.00 HCI, 426.1841; found (ESI..FT), 355.23761. Example 103: 4-[1-(3-bromophenyl)-2-pipcrazin-1-ylethyl]tetrahydro-2/-/-pyran-4-ol dihydrochloride [0333] In an analogous manner to Example 1, step 1 fe/t-butyl 4-f(3-bromophenyl)(4-hydroxvtetrahydro-2/-/-pvran-4-vl)acetvl1piperazine-1-carboxvlate was prepared from (3-bromophenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetic acid (Reference Example 1-mm) and /erf-butyl 1-piperazinecarboxylate. MS (ESI) m/z483/485 ([M+H]+); HRMS: calcd for C22H3iBrN2O5, 482.1416; found (ESI), 483.1508. [0334] In an analogous manner to Example 1, step 2 4-[1-(3-bromophenyl)-2- piperazin-1-ylethyl]tetrahydro-2H-pyran-4-ol dihydrochloride was prepared from tort- butyl 4-[(3-bromophenyl)(4-hydroxy!etrahydro-2H-pyran-4-yl)acetyl]piperazine-1- carboxylate. MS (ESI) m/z 369/371 ([M+H]4); HRMS: calcd for C17H25BrN2O2 ' 2.00 HCI, 440.0633; found (ESI), 369.1166. 124 WO 2005/037809 PCT/US2004/033090 Example 104: 1-{1-[3-(bonzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride [0335] In an analogous manner to Example 1, step 1 /erf-butyl 4-TT3-(benzvloxy)phenvH(1-hvdroxvcvclohexvl)acetyl]pipera?ine-1-carboxylate was prepared from (3-benzyloxyphenyl)(4-hydroxycyclohexyl)aceticacid (Reference Example 1-nn) and terf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 509 ([M+H]+); HRMS: calcd for CacH-oN^Os, 508.2937; found (ESI), 509.2997. [0336] In an analogous manner to Example 1, step 2 1-{1-[3-(bonzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride was prepared from terf-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-(1-(3-chlorophenyl)-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride 125 WO 2005/037809 PCT/US2004/033990 [0337] In an analogous manner to Example 1, step 1 2-(3-chlorophenyl)-2-(1 -.hvdroxvcvclohexyl]-A/-[4-(trifluoromethyl)benzyl]acetamide was prepared from (3-chlorophenyl)(1-hydroxycyc!ohexyl)acetic acid (Reference Example 1-a) and 4-trifluoromethylbenzylamine. MS (ESI) m/z 426/428 ([M+H]+). [0338] In an analogous manner to Example 1, step 2 1-(1-(3-chlorophenyl)-2-{[4-(trifluorornethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride was prepared from 2-(3-chlorophenyl)-2-(1 -hydroxycycIohexyl)-A/-[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 [0339] In an analogous manner to Example 1, step 1 1 -[2-morpholin-4-vl-1 -(2-naphthyl)-2-oxoethyl]cvclohexanol was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and morpholine. HRMS: calcdfor C22H27NO3, 353.1991; found (ESI_FT), 354.20523. [0340] In an analogous manner to Example 1, step 2 1-[2-morphoIin-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 (ESLFT), 340.2256. Example 107: 2-[1 -(3-bromophenyl)-2-piperazin-1 -ylethyl]adamantan-2-ol dihydrochloride 126 WO 2005/037809 PCT/US2004/033990 [0341] In an analogous manner to Example 1, step 1 fe/t-butyl 4-f(3-bromophenyr)(2-hvdroxv-2-adamantyl)acetyl]piperazine-1-carboxvlate was prepared from (3-bromophenyl)(2-hydroxy-2-adamantyI)acetic acid (Reference Example 1-oo) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 533/535 ([M+H]+). [0342] In an analogous manner to Example 1, step 2 2-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]adamantan-2-ol dihydrochloride was prepared from fe/f-butyl 4-[(3-bromophenyl)(2-hydroxy-2-adamantyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 419/421 ([M+H]+); HRMS: calcd for C22H3iBrN2O • 2.00 HCI, 490.1153; found (ESI), 419.1682. Example 108: 1 -[1 -[3-(benzyloxy)phenyl]-2-(4-methylpiperazin-1 -yi)ethyl]cyclohexanol dihydrochloride [0343] 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-(benzy!oxy)phenyl]-2-piperazin-1-yIethyI}cyclohexanol (see Example 104). HRMS: calcd for C26H36N2O2 ' 2.00 HCI, 480.2310; found (ESI), 409.2838. Example 109: 1-[2-morpho!in-4-yl-1-(2-naphthyl)ethyl]cyclobutanol hydrochloride 127 WO 2005/037809 PCT/US2004/033990 [0344] In an analogous manner to Example 1, step 1 1 -r2-morpholin-4-vl-1 -(2-naphthvl)-2-oxoethyl]cvclobutanol was prepared from (1-hydroxycyclobutyl)(2-naphthyl)acetic acid (Reference Example 1-c) and morpholine. HRMS: calcd for P20H23NO3, 325.1678; found (ESLFT), 326.17435. [0345] In an analogous manner to Example 1, step 2 1 -r2-morpholin-4-yl-1 -(2-naphthyl)ethyl]cyclobutanol hydrochloride was prepared from 1-[2-morpholin-4-yl-1-(2-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-yIethyl]tetrahydro-2H-pyran-4-ol dihydrochloride [0346] In an analogous manner to Example 1, step 1 fetf-butyl 4-f(3-bromo-4-methoxvphenvl)(4-hydroxytetrahvdro-2AV-pvran-4-vl)acetyl]piperazine-1-carboxylate was prepared from (3-bromo-4-methoxyphenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetic acid (Reference Example 1-pp) and fe/t-butyl 1-piperazinecarboxylate. MS (ESI) m/z 513/515 ([M+H]+); HRMS: calcd for CaaHssBirNaOe, 512.1522; found (ESI), 513.16. [0347] In an analogous manner to Example 1, step 2 4-[1-(3-bromo-4-methoxyphenyl)- 2-piperazin-1-ylethyl]tetrahydro-2/-/-pyran-4-ol dihydrochloride was prepared from tert- Ibutyl 4-[(3-bromo-4-methoxyphenyl)(4-hydroxytetrahydro-2W-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. 128 WO 2005/037809 PCT/US2004/033990 Example 111: 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol dihydrochloride [0348] In an analogous manner to Example 1, step 1 /ert-buryl 4-[[3-(benzvloxv)phenvll(1-hydroxvcvclobutyl]acetyl]piperazine-1-carboxvlate was prepared from (3-benzy!oxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-qq) and /erf-butyl 1-piperazinecarboxylate. MS (ESI) m/z481 ([M+H]+); HRMS: calcd for C28H36N2O5, 480.2624; found (ESI), 481.272. [0349] In an analogous manner to Example 1, step 2 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol dihydrochloride was prepared from terf-butyl 4-[[3-(benzyloxy)phenyl](1-hydroxycyclobutyl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C23H3oN202 • 2.00 HCI, 438.1841; found (ESI), 367.2357. Example 112: 1-[1-(3,4-dichlorophenyl)-2-morpholin-4-ylethyl]cyclohexanol hydrochloride 129 WO 2005/037809 PCT/US2004/0JJ990 [0350] In an analogous manner to Example 1, step 1 1 -[ 1 -(3.4-dichlorophenyl)-2-morpholin-4-vl-2-oxoethyllcvclohexanol was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and morpholine. HRMS: calcd for CsH^CbNCb, 371.1055; found (ESI_FT), 372.11122. [0351] In an analogous manner to Example 1, step 2 1-[1-(3,4-dichlorophenyl)-2- morpholin-4-ylethyl]cyclohexanol hydrochloride was prepared from 1-[1T(3,4- dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]cyclohexanol. HRMS: calcd for C8H25CI2NO2 • HCI, 393.1029; found (ESI_FT), 358.13358. Example 113: 1-[2-[(4-fluorobenzyl)amino]-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride 10352] In an analogous, manner to Example 1, stop 1 A/-(4-fluorobenzyl)-2-(1 -hvdroxvcyclohexvl)-2-(2-naphthyl)acetamide was prepared from (1-hydroxycyclobuty!)(2-naphthyl)acetic acid (Reference Example 1-c) and 4-fluorolbenzylamine. MS (ESI) m/z 372 ([M+H-H2O]+). [0353] In an analogous manner to Example 1, step 2 1-[2-[(4-fluorobenzyl)amino]-1-(2-naphthyl)ethyl]cyc!ohexanol hydrochloride 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. 130 WO 2005/037809 PCT/US2004/033990 Example 114: 4-[1-(3,4-dichlorophenyl)-2-morpholin-4-ylethyl]-1-mothylpipericiin-4-ol dihydrochloride [0354] In an analogous manner (o Example 1, step 1 4-[1-(3,4-dichlorophenvO-2-morpho)in-4-vl-2-oxoethylH-rnethv)piperidin-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 CieH24CI2N2O3, 386.1164; found (ESI_FT), 387.12304. [0355] In an analogous manner to Example 1, step 2 4-[1-(3,4-dichlorophenyl)-2-morpholin-4-ylethyl]-1-methylpiperidin-4-ol dihydrochlorido was prepared from 4-[1-(3,4-dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]-1-meihylpiperidin-4-ol. HRMS: calcd for C18H26CI2N2O2 • 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 [0356] In an analogous manner to Example 24, 1-[1-[3-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyc!obutanol dihydrochloride was prepared from 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-yIethyl}cyclobutanol (see Example 111). HRMS: calcd for C24H32N2O2 • 2.00 HCI, 452.1997; found (ESI), 381.2524. 131 WO 2005/037809 PC T/US2004/033990 Example 116: 4-[1-(3-bromophenyl)-2-morpholin-4-ylethyl]-1-methylpiperidin-4-ol dihydroeriioride [0357] In an analogous manner to Example 1, step 1 4-f1-(3-bromophenyl)-2-morpholin-4-yl-2-oxoethvl]-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 CisHssBrNzOg, 396.1049; found (ESI_FT), 397.11148. [0358] 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 Ci8H27BrN2O2 • HCI, 418.1023; found (ESI_FT), 383.13261. Example 117: 1 -(1 -(3-chlorophenyl)-2-(4-[(6-methoxv-2-naphthvl)methvllpiperazin-1 - yl)ethyl)cyclohexanol dihydrochloride [0359] A solution of 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) (200 mg, 0.62 mmol) and 6-methoxy-2-napthaldehyde (173 mg, 0.93 mmol) in dichloroethane (4 mL) was treated with sodium trisacetoxyborohydride (195 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 yield 194 mg (64%) 1-(1-(3- 132 WO 2005/037809 PCT/US2004/033990 chlorophenyl')-2-(4-f(6-methoxv-2-naphthyl]mcthvllpiperazin-1-vl)ethvl)cvclohexanol dihydroc'hloride as a white solid. MS (ESI) m/z 493/495 ([M+H]+); HRMS: calcd for C30H37CIN2O2 2.00 HCI, 564.2077; found (ESI_FT), 493.2632. Example 118: 1-(1-(3-chlorophenvl)-2-f4-(cvclopropylmethvl)piperazin-1-yllethyl)cyclohexanol dihydrochloridG [0360] In an analogous manner to Example 117, 1-(1-(3-chlorophenvl)-2-f4-(cyclopropvlmethyl)piperazin-1-vllethvl)cvclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-y!ethyl]cyclohexanol (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-(1-(3-chlorophenvl)-2-[4-(cvclohex-3-en-1-vlmethyl)piperazin-1- yllethyllcyclohexanol dihydrochloride [0361] In an analogous manner to Example 117, 1-(1-(3-chlorophenyl)-2-f4-(cyclohex-3-en-1-vlmethvl)piperazin-1-yl]ethyl)cvclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-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. 133 WO 2005/037809 PCT/US2004/033990 Example 120: 6-((4-[2-(3-chlorophenyl)-2-(1 -hvdroxvcvclohexvl)ethvl]piperazin-1 -vl)methyl)tetrahvdro-2H-pvran-2-ol dihydrochloride [0362] In an analogous manner to Example 117, 6-((4-[2-(3-chlorophenvl)-2-(1 -hvdroxvcvclohexvl)ethvl|piperazin-1-yl)methyl)tetrahvdro-2rt-pyran-2-ol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-y!ethyl]cyclohexanol (see Example 1) and 3,4-dihydro-2H-pyran-2-carboxaldehyde. HRMS: calcd for C24H37CIN2O3 • 2.00 HCI, 508.2026; found (ESI), 419.2455. Example 121: 1-(1-(3-chlorophenvl)-2-f4-(3-phenvlbutyl)piperazin-1-yl]ethyDcyclohexanol dihydrochloride [0363] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-[4-(3-phenylbutyl)piperazin-1 -vllethyllcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 3-phenylbutyraldehyde. MS (ESI) m/z455/457 ([M+H]*); HRMS: calcd for C28H39CIN2O • 2.00 HCI, 526.2284; found (ESI_FT), 455.28235. Example 122: 1-(1-(3-chlorophenvl)-2-f4-(2-phenvlGthyl)piperazin-1-yllethyl)cyclohexanol dihydrochloride 134 WO 2005/037809 PCT/US2O04/03399O [0364] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-f4-(2-phenylethyl)piperazin-1 -vliethyQcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and phenylacetaldehyde. MS (ESI) m/z427/429 ([M+H]+); HRMS: calcd for C26H35CIN2O ¦ 2.00 HCI, 498.1971; found (ESI), 427.2505. Example 123: 1-(1-(3-chlorophenvl)-2-[4-(3-phenoxvbenzyl)piperazin-1-yliethyDcvclohexanol dihydrochloride :0365] In an analogous manner to Example 117, 1-(1-(3-chlorophenyl)-2-f4-(3-phenoxvbenzvl)piperazin-1-yl]ethyl|cvclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohoxanol (see Example 1) and 3-phenoxybenzaldehyde. MS (ESI) m/z505/507 QM+H]+); HRMS: calcd for C31H37CIN2O2 2.00 HCI, 576.2077; found (ESI_FT), 505.26266. 135 Example 124: 1 -(1 -(3-chlorophenyl)-2-f4-(2-naphthylmethyl)piperazin-1 -yliethyllcyclohoxanol dihvdrochloride WO 2005/037809 PCT/US2004/033990 [0366] In an analogous manner to Example 117, 1 -{1 -(3-chlorophenyl)-2-[4-(2-naphthyimethvl)piperazin-1-vllethvl)cvclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophenyl)-2-pipGrazin-1-ylethyl]cyclohexanol (see Example 1) and 2-napthaldehyde. MS (ESI) m/z 463/465 ([M+H]+); HRMS: calcd for C29H35CIN2O • 2.00 HCI, 534.1971; found (ESI), 463.2499. Example 125: 1 -(1 -(3-chlorophenvO-244-(3-furvlmethvl)piperazin-1 -ynethyQcyclohexanol dihvdrochloride [0367] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-[4-(3-furylmethyl)piperazin-1 -yliethyDcyclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-y!ethyl]cyclohexanol (see Example 1) and 3-furaldehyde. 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-(cyclohexvlmethvl)piperazin-1 -yl]ethvljcyclohexanol dihvdrochloride [0368] In an analogous manner to Example 117, 1-{1-(3-chlorophenyl)-2-[4-(cvclohexvlmethvl)piperazin-1-vl1ethyl)cvclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophcnyl)-2-piperazin-1-ylethyl]cyclohexanol (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. 136 WO 2005/037809 PCT/US2004/033990 Example 127: 1 -(1 -(3-chlorophenyl)-2-[4-(quinolin-4-vlmethvl)piperazin-1 -yl]ethyl}cyclohexanol dihvdrochloride [0369] In an analogous manner to Example 117, 1-(H3-chlorophenyl)-2-f4-(quinolin-4-ylmethyl)piperazin-1 -yliethyl)cyclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 4-quinolinecarboxaldehyde. MS (ESI) m/z464/466 ([M+H]+); HRMS: calcd for C28H34CIN3O • 3.00 HCI, 571.1691; found (ESI_FT), 464.24693. Example 128: 1-(1-(3-chlorophenvl)-2-(4-r(5-ethvl-2-furv0mGthvl1piperazin-1- yl)ethyl)cvclohexanol dihvdrochloride [0370] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-(4-f(5-ethvl-2-furvl)methvHpiperazin-1 -yl)ethvl)cyclohexanol dihydrochlorido was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexano! (see Example 1) and 5-ethyl-2-f jraldehyde. MS (ESI) m/z [M+H]+ (431/433); HRMS: calcd for CO5H35CIN2O2 • 2.00 HCI, 502.1921; found (ESI), 431.2454. Example 129: 1 -(1 -(3-chlorophenvl)-2-[4-(2-phenvlpropyl)p)perazin-1 -yllethvUcyclohexanol dihvdrochloride 137 WO 2005/037809 PCT/US2004/033990 [0371] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenvl)-2-f4-(2-phenvlpropvl)piperazin-1-vl1ethvllcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 2-phenylpropionaldehyde. 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-f4-(1 -benzofuran-2-ylmethyl)piperazin-1 -yll-1 -(3-chlorophenyl)ethylicyclohexanol dihydrochloride [0372] In an analogous manner to Example 117, 1 -[2-f4-( 1 -benzofuran-2-ylmethyQpiperazin-1 -yli-1 -(3-chlorophenyl)ethvllcvclohexanol dihydrochloride was orepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and benzo[B]furan-2-carboxaldehyde. MS (ESI) m/z [M+H]+ (453/455); HRMS: calcd for C27H3SCIN2O2 • 2.00 HCI, 524.1764; found (ESI), 453.2296. 138 Example 131: 1-[2-(4-f4-(benzyloxy)bcnzyllpiperazin-1-yl)-1-(3-chloroohenyl)ethvllcyclohexanol dihydrochloride WO 2003/037809 PCT/US2004/033990 [0373] In an analogous manner to Example 117, 1-[2-(4-[4- (benzyloxv)benzylipiperazin-i -yl)-1 -O-chlorophenyl)ethyllcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 4-benzyloxybenzaldehyde. 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-(1-(3-chloroph.envl)-2-[4-(4-phenoxvbenzvl)piperazin-1-ynethyllcyclohexanol dihydrochloride [0374] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-[4-(4-phenoxybenzyl)piperazin-1 -yl]ethyllcyclohexanol 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]4); HRMS: calcd forC3iH37CIN2O2 2.00 HCI, 576.2077; found (ESI_FT), 505.26224. Example 133: 1 -(1 -(3-chlorophenvl)-2-f4-(pvridin-4-ylmethyl)piperazin-1 -vliethyDcyclohexanol dihydrochloride [0375] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenvl)-2-[4-(pyridin-4-vlmethvl)piperazin-1 -yliethyDcvclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 4-pyridinecarboxaldehyde. MS (ESI) m/z [M+H]+ (414/416); HRMS: calcd for C24H32CIN3O • 2.00 HCI, 485.1767; found (ESI), 414.2307. 139 WO 2005/037809 PCT/US2004/033990 Example 134 : 1-(1-(3-chlorophenyl]-2-r4-(pyridin-3-vlmethvl)piperazin-1-yllethyl)cvclohexanol dihydrochloride [0376] In an analogous manner to Example 117, 1-{1-(3-chlorophcnyl)-2-[4-(pyridin-3-ylmethyl)piperazin-1-yl]ethyl}cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-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-vl)-2-piperazin-1-vlethvl1cvclohexanol dihydrochloride [0377] Step 1: In an analogous manner to Example 1, step 1 ter/-butyl 4-[(3-bromophenyl)(1-hvdroxvcvclohexyl)acetvllpiperazine-1-carboxylate was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and /erf-butyl 1-piperazinecarboxylate. HRMS: calcd for C23H33BrN2C>4, 480.1624; found (ESI_FT), 481.16857. [0378] Step 2: A solution of /erf-butyl 4-[(3-bromophenyl)(1- nydroxycyclohexyl)acetyl]piperazine-1-carboxylate (2.12 g, 4.40 mmol) in dry 140 WO 2005/037809 PCT/US2004/033990 tetrahyckofuran (10 ml_) under nitrogen was treated dropwise with a solution of borane (1.0 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 (15 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 yield 2.02 g (98%) tert-butyl 4-[2-(3-brornophenvl)-2-(1-hydroxvcvclohexyl)ethyl]piperazine-1-carboxylate as a white powder. MS (ESI) m/z 467/469 ([M+H]+); HRMS: calcd for C^HssBr^Oa, 466.1831; found (ESI), 467.1899; Anal. Calcd for C^HasBrt^Oa: C, 59.10; H, 7.55; N, 5.99. Found: C, 59.14; H, 7.72; N, 5.77. [0379] Step 3: A mixture of tert-butyl 4-[2-(3-bromophenyl)-2-(1- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (0.72 g, 1.55 mmol) and tetrakis(tripheny!phosphine)palladium (37 mg, 0.032 mmol, 10 mo!%) in 1,2-dimethoxyethane (30 mL) was stirred for 10 min at room temperature. To this mixture was added sequentially 3,4-dichlorophenyl 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 yield 0.55 g (67%) of tert-butvl 4-[2-(3'.4'-dichloro-biphenyl-3-yl)-2-(1 -hydroxvcyclohexyl)ethylipiperazine-1 -carboxylate as a foam, which was used as such in the next step. ,0380] Step 4: tert-butyl 4-[2-(3',4'-dichloro-biphenyl-3-yl)-2-(1- nydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (0.39 g 0.73 mmol) was dissolved in diethyl ether (15 mL) then a 2N ethereal solution of hydrochloric acid (10 mL) was added. Methanol (approximately 1 mL) was then added until the resulting precipitate 141 WO 2005/037809 PCT/US2004/033990 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 yield 0.28 g (81%) of 1 -f 1 -(3'.4'-dichloro-1,1 '-biphenvl-3-vl)-2-piperazin-1 -vlethvHcvclohexanol dihvdrochloride as a white solid. MS (ESI) m/z 433/435/437 ((M+H]+); HRMS: calcd for C24H3oN2OCl2 • 2.00 HCI, 433.1813; found (ESI), 433.1813 Example 136: 1 -f 1 -(1.1 '-biphenyl-3-vO-2-piperazin-1 -vlethvlicyclohexanol dihvdrochloride [0381] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(1.1'-biphenyl-3- yl)-2-(1 -hydroxvcvclohexvOethvlipiperazine-i -carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 135, step 2) and phenyl boronic acid. [0382] In an analogous manner to Example 135, step 4 1 -[1 -(1,1 '-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihvdrochloride was prepared from tort-butyl 4-[2-(1,1'-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-f1-(4'-chloro-1,1'-biphenvl-3-vl)-2-piperazin-1-ylethyl]cyclohexanol 142 dihvdrochloride WO 2005/037809 PCT/US2OO4/03399O [0387] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'-chloro-biphenvl-3-vl)-2-(1-hvdroxvcvclohexyl)ethyl]piperazine-1-carboxvlate 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. [0388] In an analogous manner to Example 135, step 4 1 -[ 1 -(3'-ch)oro-1,1 '-biphenyl-3- yl)-2-piperazin-1-ylethyl]cyclohexanol dihyorochloride was prepared from tert-butyl 4-[2- (3'-chloro-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 399/401 ([M+H]+); HRMS: calcd for C2.iH3iCIN2O • 2.00 HCI, 470.1658; found (ESI), 399.2183. Example 140: 1-[1-(2'-fluoro-1,1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol maleate [0389] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(2'-fluoro-biphenvl-3-vl)-2-(1-hydroxycvclohexvl)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 2-florophenyl boronic acid. [3390] In an analogous manner to Example 135, step 4 1 -f 1 -(2'-fluoro-1.1 '-biphenvl-3- yl)-2-piperazin-1 -vlethylicyclohexanol 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 yield 1-f1-(2'-fluoro- 144 WO 2005/037S09 PCT/US2OO4/033990 1.i'-bipiyenvl-3-vl)-2-pipera?in-1-vlethyl]cvclohexanol maleate as a colorless solid. MS (ESI) m/z 383 ([M+HJ+); 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-ri-(2.5-dichlorothien-3-vl)-2-pipGrazine-1-vlethyl]cyclohexanol dihydrochloride [0391] Step 1: A solution of 3-thiophene acetic acid (1.42 g, 10.0 mmol) in acetic acid (10 ml_) was treated with N-chlorosuccinimide (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]-). [0392] Step 2: In an analogous manner to Example 1, step 1 tert-butyl 4-[(2.5-dichlorothien-3-vl)acetyl]piperazine-1-carboxvlate was prepared from 2,5-dichlorothiophene-3-acetic acid and tert-butyl 1-piperazinecarboxylate. The product was crystallized from ethyl acetate: hexane to yield a colorless solid. [0393] Step 3: A solution of diisopropyl amine (0.80 ml_, 5.6 mmol) in dry tetrahydrofuran (10mt_) under nitrogen was cooled to -78 °C and treated dropwise with a solution of n-butyllithium (1.6 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- 145 WO 2005/O37809 PCT/US2004/033990 carboxylate (1.7 g, 4.5 mmol) in tetrahydrofuran (10 ml_). After the addition was complete, the solution was stirred for 0.5 hr at -78 °C whereupon cyclohexanone (0.57 mL, 5.6 mmol) 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 (1x10 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 -hydroxvcvclohexyl)acetvllpiperazine-1-carboxvlate as a white foam. MS (ESI) m/z 477/479/481 ([M+H]), HRMS: calcd for C^oC^CS, 476.1303; found (ESI), 477.1362. [0394] Step 4: In an analogous manner to Example 135, Step 2 tert-butvl 4-[2-(2.5-dichlorothien-3-vl)-2-(1-hvdroxvcvclohexyl]ethvl1piperazine-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 C2iH3?Cl2N2O3S, 462.1511; found (ESI), 463.1594. [0395] Step 5: In an analogous manner to Example 135, step 4 1 -[1 -(2.5-dichlorothien-3-vl)-2-piperazine-1-vlethvl]cvclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(2,5-dichlorothien-3-yl)-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 C,6H24CI2N2OS ¦ 2.00 HCI, 434.0520; found (ESI), 363.1035. Example 142: 1-f1-(5-chlorothien-2-yl]-2-piperazin-1-vlethyllcvclohGxanol 146 dihvdrochloride [0398] In an analoguous manner to Example 1, step 2 1 -[1 -(5-chlorothien-2-yl)-2-piperazin-i-vlethvllcyclohexanol 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 Ci6H25CIN2OS • 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-vl)-2-piperazin-1-ylethvl1cvclohexanol dihydrochloride [0399] 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) [0400] In an analogous manner to Example 1, step 1, tert-butyl 4-f(5-bromothien-2-vl)(1-hydroxvcvclohexyl)acetyl1piperazine-1-carboxvlate 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]+ 147 WO 2005/037809 PCT/US2004/033990 [0396] -in an analogous manner to Example 141, step 1 (5-chlorothien-3-yl)acetic acid wasprepared from 2-thiophene acetic acid and N-chlorosuccinimide. (This acid was used in Reference Example 1-rr) MS (ES) m/z 175.0 ([M-H]-) [0397] In an analogous manner to Example 1, step 1 tert-butyl 4-[(5-chlorothien-2-vl)(1-hvdroxvcvclohexyl)acetvHpiperazine-1-carboxvlate was prepared from (5-chlorothien-2-yl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-rr) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 443/445 ([M+H]+) [0398] In an analoguous manner to Example 1, step 2 1 -f 1 -(5-chlorothien-2-yl)-2-piperazin-1-ylethyl]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 deH^CINoOS • 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-f1-(5-bromothien-2-vl)-2-piperazin-1-vlethyllcvclohexanol dihydrochloride [0399] 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) [0400] In an analogous manner to Example 1, step 1, tert-butyl 4-f(5-bromothien-2-yl)(1 -hydroxvcvclohexvl)acetyl]piperazine-1 -carboxylate was prepared from (5-bromothien-2-y!)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-ss) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 487/489 ([M+H]+ 147 WO 2005/037S09 PCI7US2004/033990 [0401] In an analogous manner to Example 1, step 2, 1 -f1 -(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, 5.60. Example 144: 1-f1-(5-chlorothien-3-vl)-2-piperazin-1-ylethyncvclohexanol dihydrochloride [0402] In an analogous manner to Example 1, step 1 tert-butyl 4-[(5-chlorothien-3-yOacetylipiperazine-i-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 [0403] In an analogous manner to Example 141, step 3, tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1 -hydroxycyclohexypethvlipiperazine-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 CaiHfeaCINzOsS, 428.1900; found (ESI), 429.1973. [0404] In an analogous manner to Example 135, step 2, tert-butyl 4-[2-(5-chlorothien-3-vl)-2-(1-hvdroxvcvclohexvl)ethyllpiperazine-1-carboxylate was prepared from tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohoxyl)ethyl]piperazine-1-carboxylate. [0405] In an analogous manner to Example 135, step 4 1 -f 1 -(5-chlorothien-3-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 2 Monyurzi, R.; Ubassi, G.; Pmza, M.; Pifferi, G. Synthesis of new a-hydra7inoarylacetjc acids and derivatives. Farmaco, Ed^ione Sciertifxa (1976), 3!(8), 5-19-60 148 WO 2005/037809 PCT/US2004/033990 329/33.1 ([M+H]1); HRMS: calcd for C16H25C1N2OS ' 2.00 HCI, 400.0910; found (ESI), 329.1444. Example 145: 1-[2-(4-aminopiperidin-1-yl)-1-(5-chlorothien-3-y))ethyl]cydohexanol dihydrochloride [0406] In an analogous manner to Example 1, step 1 tert-butylf1-[2-(5-chloro-thiophen-3-yl)-acetyl]-piperidin-4-yl)-carbamate was prepared from 5-chlorothiophene-3-acetic acid and 4-N-boc-aminopiperidine. [0407] In an analogous manner to Example 141, step 3, tert-butyl{1 -[2-(5-chloro- thiophen-3-yl)(1-hydroxycyclohexyl)acetvl]-piperidin-4-yl}-carbamate was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)-acetyl]-piperidin-4-yl}-carbamate and cyclohexanone. [0408] In an analogous manner to Example 135, step 2, tert-butyl(1 -[2-(5-chloro-thiophen-3-vl)(1-hvdroxycvclohexyl)ethvl]-piperidin-4-yl}-carbamate was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)(1-hydroxycyclohexyl)acetyl]-piperidin-4-y!}-carbamate.) [0409] In an analogous manner to Example 135, step 4 1 -[2-(4-aminopiperidin-1 -yQ-1 -(5-chlorothien-3-vl)ethyncyclohexanol dihydrochloride was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)(1 -hydroxycyclohexy!)ethyl)-piperidin-4-yi}"Carbamate. MS (ESI) m/z 343/345 ([M+H]+); HRMS: calcd for C17H27CIN2OS ¦ 2.00 HCI, 414.1066; found (ESI), 343.1594. Example 146: 1 -[1 -(1 -benzothien-3-y()-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride 149 WO 2005/037809 PCT/US2004/033990 [0410] In an analogous manner to Example 1, step 1 t-butyl 4-M-f1-(1-benzothien-3-yl)(1 -hydroxycyclohexvOacetyllpiperazine-i -carboxylate was prepared from 1-benzothien-3-yl(1-hydroxycyclohexyl)acetic acid (Reference Example 1-tt) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 487/489 ([M+H]+ [0411] In an analoguous manner to Example 1, step 2 1 -f1 -(1 -benzothien-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from t-butyl 4-[1-[1-(1-benzothien-3-yl)(1-hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z [M+H]+ (345); HRMS: calcd for C20H26N2OS • 2.00 HCI, 416.1456; found (ESI), 345.2024 Example 147: 1-[1-(3'.4'-difluoro-1.1'-biphenyl-3-vl)-2-piperazin-1-ylethyl]cvclohexanol dihydrochloride [0412] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3',4'-difluoro-biphenvl-3-vO-2-(1-hvdroxvcyclohexvl)ethvHpiperazinc-1-carboxvlate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (see Example 135, step 2) and 3,4-difluorophenyl boronic acid. .'0413] In an analogous manner to Example 135, step 4 1-[1-(3',4'-difluoro-1.1'-biphenvl-3-yl)-2-piperazin-1-vlethvl1cyclohexanol dihvdrochloride was prepared from lert-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 C24H30[2N2O ¦ 2.00 HCI, 472.1860; found (ESI), 401.2378 150 WO 2005/037809 PCT/US2004/033990 Example 148: 1-[1-(3',4'-dichloro-1,1'-biphenyl-2-vl)-2-piperazin-1-vlethvl]cvclohexanol dihydrochloride [0414] In an analogous manner to Example 1, step 1 tert-butyl 4-f(2-bromophenyl)(1-hydroxvcvclohexyDacetvllpiperazine-i-carboxylate was prepared from (2-bromophenyl)(1-hydroxycyclohcxyl)acetic acid (Reference Example 1-uu) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 481/483 ([M+H]+); HRMS: calcd for C23H33BrN2Oa, 480.1624; found (ESI), 481.1689 [0415] In an analoguous manner to Example 135, step 2, tert-butyl 4-[2-(2- bromophenyl)-2-(1-hvdroxvcvclohexyl)ethvl]piperazine-1-carboxvlate was prepared from tert-butyl 4-[(2-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylatc. MS (ESI) m/z 467/469 ([M+H]+); HRMS: calcd for C23H35BrN2O3, 466.1831; found (ESI), 467.1895; [0416] In an analogous manner to Example 135, step 3 tert-butyl 4-[3'4'dichloro-1.1'-biphenvl-2-vl)-2-(1-hvdroxvcvclohexvl)ethynpiporazine-1-carboxvlate was prepared from tert-butyl 4-[2-(2-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylato and 3,4-dichloro phenyl boronic acid. [0417] In an analogous manner to Example 135, step 4 1-[1-(3'.4'-dichloro-1,V-biphenyl-2-yl)-2-piperazin-1-y!ethyl]cyclohexanol 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 C24H3oCI2N20 • 2.00 HCI, 504.1269; found (ESI), 433.1797 151 WO 2005/037809 PCT/US2004/033990 -Example 149: 1 -f 1 -(1,1 '-biphenvl-2-yl)-2-piperazin-1 -ylethyllcvclohexanol dihydrochloride [0418] In an analogous manner to Example 135, step 3 tert-butyl 4-f 1,1 '-biphenyl-2-yQ-2-(1-hydroxvcyclohexvl)ethyllpiperazine-1-carboxvlate 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. [0419] In an analogous manner to Example 135, step 4 1 -[1 -(1,1 '-biphenyl-2-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[1,1'-biphenyl-2-yl)-2-(1-hydroxycyclohoxyl)cthyl]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 '-bipheny!-2-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0420] In an analogous manner to Example 135, step 3 tert-butyl 4-f3'-chloro-1.1'-biphenvl-2-vl)-2-(1-hvdroxycyclohexvl)ethvl[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-ch!oro phenyl boronic acid. 152 WO 2005/037809 PCT/US2004/033990 [0421] In an analogous manner to Example 135, step 4 1-f1-(3'-chloro-1,1'-biphenyl-2-yl)-2-piperazin-1 -vlethvlicvclohexanol dihvdrochlorido was prepared from tort-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 C2/.H3iCIN2O ¦ 2.00 HCI, 470.1658; found (ESI), 399.2211 Example 151:1 -{1 -[2-(1,3-benzodioxol-5-yl)phenyl]-2-piperazin-1 -ylethyljcyclohexanol dihydrochloride [0422] In an analogous manner to Example 135, step 3 tort-butyl 4-f1-(1.3- benzodioxol-5-vlphenvl)-2-(1-hydroxvcvclohexvl)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. [0423] In an analogous manner to Example 135, step 4 1 -(1 -[2-(1.3-benzodioxol-5- yl)phenyl1-2-piperazin-1 -ylethyllcyclohexanol dihydrochloride was prepared from tert- butyl 4-[1-(1,3-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-aminopiperid'm-1 -yl)-1 -(3'.4'-dichloro-1.1 '-biphenyl-3-yl)ethyncyclohexanol dihydrochloride 153 WO 2005/037809 PCT/US2OO4/033990 [0424] In an analogous manner to Example 135, step 3 tert-butyl (1-f(3'.4'-dichloro-1.1'-biphenvl-3-vl)f1-hvdroxvcvclohexyl]acetynpiperidin-4-vl)carbamato was prepared from_ferf-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 C30H38CI2N2O4, 560.2209; found (ESI), 561.2263 [0425] In an analogous manner to Example 135, step 2 tort-butyl (1 -[2-(3'.4'-dichloro-1.1'-biphenvl-3-vl)-2-(1-hvdroxvcyclohexvl)ethyllpiperidin-4-vl)carbamate was prepared from tert-butyl {1-[(3',4'-dichloro-1,1'-biphenyl-3-yl)(1-hydroxycyclohexyl)acetyl]piporidin-4-yl}carbamate. MS (ES) m/z 547.3 ([M+HJ+); HRMS: calcd for C30H40CI2N2O3, 546.2416; found (ESI), 547.2473. [0426] In an analogous manner to Example 135, step 3 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3',4'-dichloro-1.1 '-biphenyl-3-vl)ethvllcvclohexanol 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 C2bH32CI2N2O • 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 [0427] In an analogous manner to Example 1, step 1 terf-butyl 4-f(3-bromophenyl)(1-hydroxvcvclobutyDacetvlipiperazine-i -carboxylate was prepared (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and ter/-butyl 1- 154 WO 2005/037809 PCT/US2004/033990 piperazinecarboxylate. HRMS: calcd forC21H29BrN2O4, 452.1311; found (ESI_FT), 453.13746. [0428] In an analogous manner to Example 135, step 2 terf-butvl 4-[2-(3-bromophenvl)-2-(1-hvdroxvcvclobutvl)ethvi|piperazine-1-carboxvlate was prepared from tert-bu\y\ 4-[(3-bromophenyl)(1 -hydroxycyclobutyl)acetyl]piperazine-1 -carboxylate and 3,4-dichloro phenyl boronic acid. [0429] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'.4'-dichloro-biphenvl-3-vl)-2-(1-hvdroxvcvclobutvl)ethvl]pipera7.ine-1-carboxvlate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1 -hydroxycyclobutyl)ethyl]piperazine-1 -carboxylate and 3,4-dichloro phenyl boronic acid. [0430] In an analogous manner to Example 135, step 4 1-M-(3'.4'-dichtoro-1.1'-biphenyl-3-yl)-2-piperazin-1-vlethvHcvclobutanol 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-f1-(1-methyl-1 H-indol-3-yl)-2-piperazin-1-vlethvl]cyclohexanol dihydrochloride [0431] In an analogous manner to Example 1, step 1 tert-butyl 4-R1- hydroxycyclohexyl)d -methyl-1 H-indol-3-yl)acetynpiperazine-1 -carboxylate was orepared from (1-methyl-1 H-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 CssHs/NsO*. 455.2784; found (ESI_FT), 456.28501. 155 WO 2005/037809 PCT/US2004/033990 [0432] . In an analogous manner to Example 1, step 2 1-M-(1-methvl-1H-inclol-3-vl)-2-pipera2ifl-1 -ylethvlicyclohexanol dihvdrochloride was prepared from tert-butyl 4-[(1-hydroxycyclohexyl)(1 -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-f1-(1H-indol-3-vl)-2-piperazin-1-vlethvl1cyclohexanol dihydrochloride [0433] In an analogous manner to Example 1, step 1 tert-butyl 4-[(1- hydroxycyclohexvlH 1 -(tert-butvl-dimethyl-silanyl)-1 H-indol-3-yl)acetyHpiperazine-1 - carboxylate was prepared from (1-(tert-Butyl-dimethyl-silanyl)-1H-indol-3-yl) (1-hydroxycylclohexyl) acetic acid (Reference Example 1-yy) and tert-butyl 1-piperazinecarboxylate. [0434] In an analogous manner to Example 1, step 2 1 -f 1 -(1 /-/-indol-3-yl)-2-piperazin-1 -ylethvlicyclohexanol dihvdrochloride was prepared from tert-butyl 4-[(1-hydroxycyclohexyl)(1-(tort-butyl-dimethyl-silanyl)-1H-indol-3-yl)acGtyl]piperazine-1-carboxylate. MS (ESI) m/z 328 ([M+H]+); HRMS: calcd for C2oH29N30 ' 2.00 HCI, 399.1844; found (ESI_FT), 328.23696 Example 156: 1 -f 1 -[2-chlorothien-3-yl)-2-piperazin-1 -ylethyllcyclohexanol 156 dihvdrochloride WO 2005/037809 PCT/US2004/033990 [0435] ln an analogous manner to Example 141, step 1 (2-chlorothien-3-v0acetic 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-f(2-chlorothien-3-yl)acetvlipiperazine-1-carboxylato was prepared from (2-chlorothien-3-yl)acetic acid_and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 289.0 ([M+H-C4H8J+); HRMS: calcd for C15H21CIN2O3S, 344.0961; found (ESI), 345.1057. [0436] In an analogous manner to Example 141, step 3 tert-butyl 4-f(2-chlorothien-3-yl)(1-hydroxvcvclohexyl)acetyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[(2-chlorothien-3-yl)acetyl]piperazine-1 -carboxylate and cyclohexanone. [0437] In an anlogous manner to Example 135, step 2 tert-butyl 4-[2-(2-chlorothien-3-vl)-2-(1-hvdroxvcvclohoxvl)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+HJ+); HRMS: calcd for CaiHaaCINsOaS, 428.1900; found (ESI), 429.1967 [0438] In an analogous manner to Example 135, step 4 1 -f 1 -(2-chlorothien-3-yl)-2-piperazine-1 -vlethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(2-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 329/331 ([M+H]+); HRMS: calcd for C16H25C1N2OS • 2.00 HCI, 400.0910; found (ESI), 329.1442. Example 157: 1 -[1 -(1.1 '-biphenyl-4-yl)-2-piperazin-1 -vlethvlicyclohexanol 157 dihydrochloride WO 2005/037809 PCT/US2004/033990 [0439] In an analogous manner to Example 1, step 1 tert-butyl 4-[1,1 '-biphenyl-4-yin -hvdroxvcvclohexyl)acetvl1pipeiazine-1-carboxvlate was prepared from (1-hydroxycyclohexyl)(1,1'-biphenyl-4-yl)acGtic acid (Reference Example 1-zz) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 479 ([M+H]+); Anal. Calcd for C?DH38N2O.i: C, 72.77; H, 8.00; N, 5.85. Found: C, 72.69; H, 8.39; N, 5.80. [0440] In an analogous manner to Example 13, step 2 1 -f 1 -(1.1 '-biphenyl-4-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[1,1'-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-(1,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1-ylethyl]cyclohexanol dihydrochloride WO 2005/037800 PCT/US2004/033990 [0265] In an analogous manner to Example 1, step 1 ferf-butyl 4(1- hvdroxvcvclohexyl](2-naphthvl)acetvllpiperazine-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]+). [0266] In an analogous manner to Example 1, step 2 1-[1-(2-naphthy))-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from /erf-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 [0267] 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 (sec Example 63). MS (ESI) m/z 353 ([M+H]+); HRMS: calcd for C23H32N2O • 2.00 HCI, 424.2048; found (ESl_FT), 353.25994. Example 65: 2-(3-bromo-4-methoxyphenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol dihydrochloride [0268] In an analogous manner to Example 1, step 1 ferf-butyl 4-[2-(3-bromo-4-methoxvphenvO-3-ethvl-3-hvdroxypentanoyl]piperazine-1-carboxvlate was prepared from 2-(3-bromo-4-methoxyphenyl)-3-ethyl-3-hydroxypentanoic acid (Reference 103 WO 2005/037809 PCT/US2004/033990 Example 1-y) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 499/501 ([M+H]+); HRMSrtalcd for C23H35BrN2O5, 498.1729; found (ESI), 499.1793. [0269] 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 C18H2oBrN202 • 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 [0270] 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 '0271] In an analogous manner to Example 1, step 1 2-(3-chlorophenvl)-A/-cvclohexyl-2-(1-hvdroxvcvclohexyl)acetamide was prepared from (3-chlorophenyl)(1- 104 WO 2005/037800 PCT/US2004/033990 hydro>;ycyclohexyl)acetic acid (Reference Example 1-a) and cyclohexylamine. MS (ESI) m/z 350/352 ([M+H]+). [0272] In an analogous manner to Example 1, step 2 1-[1-(3-chlorophenyl)-2-(cyclohexylamino)ethyl]cyc!ohexanol hydrochloride was prepared from 2-(3-chlorophenyl)-A/-cyclohexyl-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z 336/338 ([M+H]+); HRMS: calcd for C20H3cCINO • HCI, 371.1783; found (ESI), 336.206. Example 68: 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclobutanol dihydrochloride [0273] In an analogous manner to Example 1, step 1 fert-butyl 4-fd- hvdroxvcvclobutvl)(1-naphthyl)acetvllpiperazine-1-carboxvlate was prepared from (1-hydroxycyclobutyl)(1-naphthyl)acetic acid (Reference Example 1-o) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z425 ([M+H]+). [0274] In an analogous manner to Example 1, step 2 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclobutanol dihydrochloride was prepared from /erf-butyl 4-[(1-hydroxycyclobutyl)(1-naphthyl)acetyl]piperazine-1-carboxylato. MS (ESI) m/z 311 ([M+H]*); HRMS: calcd for C20H26N2O • 2.00 HCI, 382.1579; found (ESI), 311.2127. Example 69: 1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclobutanol dihydrochloride 105 WO 2005/037809 PCT/US2004/033990 [0275] In an analogous manner to Example 24, 1-[2-(4-methylpiperazin-1-yl)-1-(1-naphtli^!)ethyl]cyclobutanol dihydrochloride was prepared from 1-[i-(1-naphthyl)-2-piperazin-1-y)eihy)]cyclobutanol (see Example 68). MS (ES) m/z 325.3 ((M+H]+); HRMS: calcd for C2iH28N2O ¦ 2.00 HCI, 396.1735; found (ESI), 325.2278. Example 70: 1-{1-[4-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol dihydrochloride [0276] In an analogous manner to Example 1, step 1 /erf-butyl 4-[[4- (benzvloxv)phenvl1(1-hvdroxvcvclobutyl)acetyl]piperazine-1-carboxvlate 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 CaaHaeNsOs, 480.2624; found (ESI), 481.2716. [0277] In an analogous manner to Example 1, step 2 1-{1-[4-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyc!obutanol dihydrochloride was prepared from /erf-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 mr. WO 2005/037S09 PCT/US2004/033990 [0278] 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 [0279] In an analogous manner to Example 1, step 1 te/t-butyl 4-[1-(3-chlorophenvlphenvl)(1-hvdroxvdecahvdronapthvl)acetyl1piperazine-1-carboxvlate was prepared from (3-chlorophenyl)(1-hydroxydecahydronapthyl)acetic acid (Reference Example 1-aa) and terf-butyl 1-piperazinecarboxylate. MS (ESI) m/z491/493 ([M+H]+). [0280] In an analogous manner to Example 1, step 2 1-[1-(3-chlorophenyl)-2- piperazin-1-y]ethyl]decahydronaphthalen-1-ol dihydrochloride was prepared from tert- butyl 4-[1-(3-chlorophenylphenyl)(1-hydroxydecahydronapthyl)acetyl]piperazine-1- carboxylate. MS (ES) m/z 377.3 ([M+H]4); HRMS: calcd for C2?H33CIN2O • 2.00 HCI, 448.1815; found (ESI), 377.2351. Example 73: 1-[1-(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazin-1-yl)ethyl]-4-terf-butylcyclohexanol dihydrochloride 107 WO 2005/037809 PCT/US2004/033990 [0281] In an analogous manner to Example 1, step 1 1-M-(3-bromo-4-methoxyphenvl)-2-(4-methvlpiperazin-1-vl)-2-oxoethyl]-4-tert-butylcvclohexanol was prepared from (3-bromo-4-methoxyphenyl)(4-/£?rt-butyl-1 -hydroxycyclohexyl)acetic acid (Reference Example 1-bb) and A/-methylpiperazine. MS (ESI) m/z 481/483 ([M+H]+). [0282] In an analogous manner to Example 1, step 2 1-[1-(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazin-1-yl)ethyl]-4-terf-butylcyclohexanol dihydrochloride was prepared from /erf-butyl 1 -[1 -(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazin-1 -yl)-2-oxoethyl]-4-terf-butylcyclohexanol. MS (ESI) m/z 467/469 ([M+H]+); HRMS: calcd for Ca^BrlNbC^ ¦ 2.00 HCI, 538.1728; found (ESI), 467.2258. Example 74: 2-[1 -(3-chlorophenyl)-2-piperazin-1 -ylethyl]decahydronaphthalen-2-ol dihydrochloride [0283] In an analogous manner to Example 1, step 1 fert-butyl 4-f1-(3-chlorophenvlphenyl)(2-hydroxvdecahydronapthvl)acetyl]piperazine-1-carboxylate was prepared from (3-chlorophenyl)(2-hydroxydccahydronapthyl)acetic acid (Reference Example 1-cc) and /erf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 491/493 ([M+H]+). [0284] In an analogous manner to Example 1, step 2 2-[1-(3-chlorophenyl)-2- piperazin-1-ylethyl]dccahydronaphthalen-2-ol dihydrochloride was prepared from tert- butyl 4-[1 -(3-chlorophenylphenyl)(2-hydroxydecahydronapthyl)acetyl]piperazine-1 - ios WO 2005/037809 PCT/US2004/033990 caiboxylats. MS (ESI) m/z 377 ([M+H]*); HRMS: calcd for C22H33CIN2O • 2.00 HCI, 448.1815; found (ESI), 377.2346. Example 75: 1-(1-(3,4-dichlorophenyl)-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride [0285] In an analogous manner to Example 1, step 1 2-(3.4-dichlorophenyl)-2-( 1 -hvdroxvcyclohexyl)-A/-f4-(trifluoromethvl)benzvl1acGtamide was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and 4-trifluoromethylbenzylamine. MS (ESI) m/z 460/462/464 ([M+H]+). [0286] In an analogous manner to Example 1, step 2 1-(1-(3,4-dichlorophenyl)-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)cyclohexano! hydrochloride was prepared from 2-(3,4-dichlorophenyl)-2-(1-hydroxycyclohexyl)-A/-[4-(trifluoromethyl)benzyl]acetamide. MS (ESI) m/z 446/448/450 ([M+H]+); HRMS: calcd for CaaHaaClaFaNO • HCI, 481.0954; found (ESI), 446.1232; Anal. Calcd for C22H24CI2F3NO • HCI: C, 54.73; H, 5.22; N, 2.90. Found: C, 54.69; H, 4.99; N, 2.78. Example 76: 4-ferr-buryl-1-[1-(1-naphthyl)-2-pipcrazin-1-ylethyl]cyclohexanol . dihydrochloride [0287] In an analogous manner to Example 1, step 1 tert-butyl 4-[(4-fert-butyl-1-hvdroxvcvclohexyl)(1-naphthyl)acetyllpiperazine-1-carboxvlate was prepared from (4- 109 WO 2005/037809 PCT/US2004/033990 tert-butvl-1-hydroxycyclohexyl)(1-naphthyl)acetic acid (Reference Example 1-dd) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 509 ([M+H]+); HRMS: calcd for C3iH44N2O<, 508.3301; found (ESI), 509.3354. [0288J In an analogous manner to Example 1, step 2 4-te/?-butyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from fert-butyl 4-[(4-tert-butyl-1-hydroxycyclohexyl)(1-naphthyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 395 ([M+H]+); HRMS: calcd for C26H30N2O ¦ 2.00 HCI, 466.2518; found (ESI), 395.3055. Example 77: 4-[1 -(3-chlorophenyl)-2-piperazin-1 -ylethyl]tetrahydro-2H-pyran-4-ol dihydrochloride |0289] In an analogous manner to Example 1, step 1 fe/t-butyl 4-f(3-chlorophenyl)(4-hvdroxvtetrahydro-2H-pvran-4-vl)acetvllpiperazine-1-carboxylate was prepared from (3-chlorophenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetic acid (Reference Example 1-ee) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z439/441 ([M+H]*); HRMS: calcd for C22H31CIN2O5, 438.1921; found (ESI_FT), 439.19884. [0290] 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-hydroxytetrahydro-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-2fy-pyran-4-ol dihydrochloride no WO 2005/037809 PCT/US2004/033990 [0291] In an analogous manner to Example 24, 4-[1-(3-chlorophenyl)-2-(4- methylpiperazin-1-yl)ethyl]tetrahydro-2/-/-pyran-4-ol dihydrochloride was prepared from 4-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]tetrahydro-2/-/-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)ethyi]-4-terf-butylcyclohexanol dihydrochloride [0292] In an analogous manner to Example 1, step 1 1 -f 1 -(3-bromophenyl)-2-(4-methvlpipera7_in-1-vO-2-oxoethvl1-4-tert-butylcyclohexanol was prepared from (3-bromophenyl)(4-tert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-ff) and A/-methylpipcrazine. MS (ESI) m/z451/453 ([M+H]+). [0293] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]-4-fcrt-butylcyclohexanol dihydrochloride was prepared from 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)-2-oxoethyl]-4-/ert-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 in WO 2005/037809 PCT/US2004/033990 [0294] In an analogous manner to Example 1, step 1 2-(3,4-dichlorophenvl)-A/-(4-fluorobenzvl)-2-(1-hvdroxvcvclohexyl)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]+). [0295] 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)-/V-(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 [0296] In an analogous manner to Example 1, step 1 te/t-butyl 4-[2-(3-bromophenvO-3-hydroxy-3-propylhexanoyl]piperazine-1 -carboxylate was prepared from 2-(3-bromophenyl)-3-hydroxy-3-propylhexanoicacid (Reference Example 1-gg) and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 497.2 ([M+H]+). [0297] In an analogous manner to Example 1, step 2 4-[1-(3-bromophenyl)-2-piperazin-1-y!ethyl]heptan-4-ol dihydrochloride was prepared from te/t-butyl 4-[2-(3-bromophenyl)-3-hydroxy-3-propylhexanoy!]piperazine-1 -carboxylate. MS (ES) m/z 383.2 ([M+H]+); HRMS: calcd forC19H31BrN2O • 2.00 HCI, 454.1153; found (ESI), 383.1705. 112 WO 2005/037809 PCT/US2004/033990 Example 82: 4-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yI)ethyl]heptan-4-ol dihydrochloride [0298] 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 [0299] In an analogous manner to Example 1, step 1 1 -[1 -(3,4-dichlorophenyl)-2-morpholin-4-vl-2-oxoethyl]cyclobutanol was prepared from (3,4-dichlorophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-p) and morpholine. HRMS: calcd for C16H19CI2NO3) 343.0742; found (ESI_FT), 344.08102. [0300] In an analogous manner to Example 1, step 2 1-[1-(3,4-dichlorophenyl)-2- morpholin-4-ylethyl]cyc!obutanol hydrochloride was prepared from 1-[1-(3,4- dichlorophenyl)-2-morpholin-4-yl-2-oxoethyi]cyclobutanol. HRMS: calcd for C16H21CI2NO2 " HCI, 365.0716; found (ESI_FT), 330.10064. 113 WO 2005/037809 PCT/US2004/033990 Example.84:1 -[1 -(3-bromo-4-methoxyphenyl)-2-piperazin-1 -ylethyl]-4-tert-butylcyclofiexanol dihydrochloride [0301] In an analogous manner to Example 1, step 1 tert-butyl 4-[(3-bromo-4-methoxyphenvl)(4-tert-butvl-1 -hvdroxvcvclohexvl)acetyl1piperazine-1 -carboxvlate was prepared from (3-bromo-4-methoxyphenyi)(4-tert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-bb) and terf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 567/569 ([M+H]4); HRMS: calcd for C28HBrN2O5, 566.2355; found (ESI), 567.2435. [0302] In an analogous manner to Example 1, step 2 1-[1-(3-bromo-4-methoxyphenyl)-2-piperazin-1-ylethyl]-4-tert-butylcyclohexanol dihydrochloride was prepared from tert-butyl 4-[(3-bromo-4-methoxyphenyl)(4-tert-butyl-1-hydroxycycIohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 453/455 ([M+H]4); 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 [0303] In an analogous manner to Example 1, step 1 1 -[1 -(3-chlorophenyl)-2-oxo-2-piperidin-1-ylethvlicyclohexanol was prepared from (3-chlorophenyl)(1-hydrdxycyclohexyl)acetic acid (Reference Example 1-a) and piperidine. HRMS: calcd for C19H26CINO2, 335.1652; found (ESI_FT), 336.17194. [0304] In an analogous manner to Example 1, step 2 1-[i-(3-chlorophenyl)-2-piperidin-1-ylethyl]cyclohexanol hydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-oxo-2- 114 WO 2005/037809 PCT/US2004/033990 pipeririin-1-ylethyl]cyclohexanol. HRMS: calcd for C19H28CINO • HCI, 357.1626; found (ESLFT), 322.19304. Example 86: 2-(3-chlorophenyl)-1,1-dicyclopropyl-3-(4-methylpiperazin-1-yl)propan-1-ol dihydrochloride [0305] In an analogous manner to Example 1, step 1 ferf-butyl 4-r2-(3-chlorophenyl) (3,3-dicvclopropvl-3-hvdroxvpropvl)acetyl1piperazine-1-carboxvlate was prepared from 2-(3-chlorophenyl)-3,3-dicyclopropyl-3-hydroxypropanoic acid (Reference Example 1-hh) and /V-methylpiperazine. MS (ESI) m/z363 ([M+H]+). [0306] 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 fert-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 C20H29CIN2O ¦ 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 ' [0307] In an analogous manner to Example 1, step 1 fe/f-butyl 4-r(3-bromophenvl)(1-hvdroxv-3,3,5,5-tetramethvlcyclohexvl)acetyl]piperazine-1-carboxvlate was prepared 115 WO 2005/037809 PCT/US2004/033990 from (3.-bromophenyl)(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetic acid (Reference Example 1-ii) and tert-butyl 1-piperazinecarboxylate. [0308] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-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)acetyl]piperazine-1-carboxylate. MS (ES) m/z 423.2 ([M+H]+); HRMS: calcd for C22H35BrN2O1 422.1933; found (ESI), 423.2015. Example 88: 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]-3,3,5,5-tetramethylcyclohexanol dihydrochloride [0309] In an analogous manner to Example 24, 1-[1-(3-bromophenyl)-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- tetramethylcyclohexanol (see Example 87). MS (ES) m/z 437.3 ([M+Hf); 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 [0310] 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- WO 2005/037809 PCT/US2004/033990 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-(1-(3-bromophenyl)-2-{[4-"(trifluoromethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride [0311] In an analogous manner to Example 1, step 1 2-(3-bromophenyl)-2-(1 -hvdroxvcvclohexvl)-N-[4-(trifluoromethyl)benzyl]acetamide was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-trifluoromethylbenzylamine. MS (ESI) m/z470/472 ([M+H]+). [0312] In an analogous manner to Example 1, step 2 T-(1-(3-bromophenyl)-2-{[4- (trifluoromethyl)benzyl]amino}ethyl)cyc!ohexano! hydrochloride was prepared from 2-(3- bromophenyl)-2-(1-hydroxycyclohexyl)-A/-[4-(trifluoromethyl)benzyl]acetamide. MS (ESI) m/z 456/458 ([M+H]+); HRMS: calcd for C22H25BrF3NO • HCI, 491.0838; found (ESI), 456.1147. Example 91: 4-ethyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride 117 WO 2005/037809 PCT/US2004I/033990 [0313] In an analogous manner to Example 1, step 1 /erf-butyl 4-ri-(1-naphthyl)- (4-ethvl-1-hvdroxvcvclohexvl)acetvl1piperazine-1-carboxylate was prepared from (4-ethyl-1-hydroxycyclohexyl) -(1-naphthyl) acetic acid (Reference Example 1-jj) and /erf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 481 ([M+Hf); [0314] In an analogous manner to Example 1, step 2 4-ethyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from /erf-butyl 4-[1-(1-naphthyl)- (4-ethyl-1-hydroxycyclohexyl)acetyl]piperazine-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 [0315] 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 C18H25F3N2O2' 2.00 HCI, 430.1402; found (ESI), 359.1965. i Example 93: 4-ferf-butyl-1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride l is WO 2005/037809 PCT/US2004/03399O [0316] In an analogous manner to Example 1, step 1 tert-butyl 4-f(4-/ert-butyl-1-hvdroxvcvclohexvl)(3-chlorophenyl)acetyl]piperazine-1-carboxvlate was prepared from (3-chlorophenyl)(4-/ert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-kk) and /erf-butyl 1-piperazinecarboxylate. MS (ES) m/z 493.4 ([M+H]*). [0317] In an analogous manner to Example 1, step 2 4-te/t-butyl-1-[1-(3-chlorophenyl)- 2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from terf-butyl 4-[(4- fer/-butyl-1-hydroxycyclohexyl)(3-chlorophenyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 379 ([M+H]+); HRMS: calcd for C^HasCIN^O, 378.2438; found (ESI), 379.2513. Example 94:2-(3-chlorophenyl)-3-ethyl-1 -(4-methylpiperazin-1 -yl)pentan-3-ol dihydrochloride [0318] In an analogous manner to Example 24, 2-(3-chlorophenyl)-3-ethyl-1-(4-methylpiperazin-1-yl)pentan-3-ol dihydrochloride was prepared from 2-(3-chlorophenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol (see Example 52). (ESI) m/z 325/327 ([M+H]+); HRMS: calcd for C18HsSCIN2O • 2.00 HCI, 396.1502; found (ESI), 325.2032. Example 95:1-[1-(3-bromophenyl)-2-morpholin-4-ylethyl]cyclobutanol hydrochloride 119 WO 2005/037809 PCT/US2004/033990 [0319] In an analogous manner to Example 1, step 1 1 -f 1 -(3-bromophenvl)-2-morpholin-4-vl-2-oxoethvllcvclobutanol was prepared from (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and morpholine. HRMS: calcd for C16H23BrNO3, 353.0627; found (ESI._FT), 354.06919. [0320] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2- morpholin-4-ylethyl]cyclobutanol hydrochloride was prepared from to/t-butyl 4-[(4-/erf- butyl-1-hydroxycyclohexyl)(3-chlorophenyl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C16H22BrNO2 HCI, 375.0601; found (ESI_FT), 340.08898. Example 96: 1-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]-4-/erf-butylcyclohexanol dihydrochloride [0321] In an analogous manner to Example 1, step 1 /erf-butyl 4-[(3-bromophenyl)(4-/ert-butyl-1-hydroxycvclohexvl)acetyl]piperazine-1-carboxylate was prepared from (3-bromophenyl)(4-te/?-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-ff) and ferf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 537/539 ([M+H]+); HRMS: calcd for C27H4iBrN2O,., 536.2250; ^ound (ESI), 537.2324. [0322] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2- piperazin-1-ylethyl]-4-ferf-butylcyclohexanoi dihydrochloride was prepared from tert- butyl 4-[(3-bromophenyl)(4-ferf-butyl-1-hydroxycyclohexyl)acetyl]piperazine-1- 120 WO 2005/037809 PCT/US2004/033990 carboxylate. MS (ESI) m/z 423/425 ([M+H]+); HRMS: calcd for C^sBrNaO • 2.00 HCI, 494.1466; found (ESI), 423.1994. Example 97: 4-methyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0323] In an analogous manner to Example 1, step 1 tert-butyl 4-f1-(1-naphthyl)- (4-methvl-i-hydroxycvclohexyDacetvllpiperazine-i-carboxvlate was prepared from (4-methyl-1-hydroxycyclohexyl) -(1-naphthyl) acetic acid (Reference Example 1-11) and terf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 467 ([M+H]+). [0324] 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 [0325] In an analogous manner to Example 1, step 1 2-(3-bromophenyl)-A/-(4- fluorobenzyl)-2-( 1 -hydroxycyclohexvOacetamide was prepared from (3-bromophenyl)(1- 121 WO 2005/037809 PCT/US 2004/033990 hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-fluorobenzylamine. MS (ESI) m/z420/422 ([M+H]'). [0326] 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)-A/-(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 [0327] In an analogous manner to Example 1, step 1 1 -f. 1 -(3-bromophenyl)-2-morpholin-4-vl-2-oxoethyl]cyclohexanol was prepared.from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and morpholine. HRMS: calcd for Ci8H24BrNO3, 381.0940; found (ESI_FT), 382.10032. [0328] In an analogous manner to Example 1, step 2 1-[1-(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 CieH26BrNO2 HCI, 403.0914; found (ESI_FT), 368.12137. Example 100: 4-fert-butyl-1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride 122 WO 2005/037809 PCT/US2004/033990 [0329] In an analogous manner to Example 24, 4-fe/Tf-butyl-1-[2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from 4-fert-butyl-1-[1-(1-naphthy!)-2-piperazin-1-ylethyl]cyclohexanol (see Example 76). MS (ESI) m/z 409 ([M+H]+); HRMS: calcd for C27H4oN20 • 2.00 HCI, 480.2674; found (ESI), 409.3207. Example 101: 4-tert-butyI-1 -[1 -(3-chloropheny!)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride [0330] In an analogous manner to Example 24, 4-fert-butyl-1-[1-(3-chlorophenyl)-2-(4-methylpiperazin-1-yl)ethy!]cyclohexanol dihydrochloride was prepared from 4-ferf-butyl-1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 93). MS (ESI) m/z 393 ([M+H]4); HRMS: calcd for C23H37CIN2O • 2.00 HCI, 464.2128; found (ESI), 393.2673. Example 102: 1 -methyl-4-[2-morphoiin-4-yl-1 -(2-naphthyl)ethyl]piperidin-4-ol hydrochloride 123 WO 2005/037809 PCT/US2004/033990 [0331] In an analogous manner to Example 1, step 1 1 -methvl-4-[2-morpholin-4-yl-1 -(2-naphthvl)-2-oxoethyllpiperidin-4-ol was prepared from (4-hydroxy-1-methylpiperidin-4-yl)(2-naphthyl)acetic acid (Reference Example 1-x) and morpholine HRMS: calcd for C??H28N2O3, 368.2100; found (ESI_FT)t 369.21652. [0332] In an analogous manner to Example 1, step 2 1-methyl-4-[2-morpholin-4-yl-1-(2-naphthyl)ethyl]piperidin-4-ol hydrochloride was prepared from 1-methyl-4-[2-morpholin-4-y!-1-(2-naphthyl)-2-oxoethyl]p:peridin-4-ol. HRMS: calcd for C22H30N2O2 ' 2.00 HCI, 426.1841; found (ESI..FT), 355.23761. Example 103: 4-[1-(3-bromophenyl)-2-pipcrazin-1-ylethyl]tetrahydro-2/-/-pyran-4-ol dihydrochloride [0333] In an analogous manner to Example 1, step 1 fe/t-butyl 4-f(3-bromophenyl)(4-hydroxvtetrahydro-2/-/-pvran-4-vl)acetvl1piperazine-1-carboxvlate was prepared from (3-bromophenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetic acid (Reference Example 1-mm) and /erf-butyl 1-piperazinecarboxylate. MS (ESI) m/z483/485 ([M+H]+); HRMS: calcd for C22H3iBrN2O5, 482.1416; found (ESI), 483.1508. [0334] In an analogous manner to Example 1, step 2 4-[1-(3-bromophenyl)-2- piperazin-1-ylethyl]tetrahydro-2H-pyran-4-ol dihydrochloride was prepared from tort- butyl 4-[(3-bromophenyl)(4-hydroxy!etrahydro-2H-pyran-4-yl)acetyl]piperazine-1- carboxylate. MS (ESI) m/z 369/371 ([M+H]4); HRMS: calcd for C17H25BrN2O2 ' 2.00 HCI, 440.0633; found (ESI), 369.1166. 124 WO 2005/037809 PCT/US2004/033090 Example 104: 1-{1-[3-(bonzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride [0335] In an analogous manner to Example 1, step 1 /erf-butyl 4-TT3-(benzvloxy)phenvH(1-hvdroxvcvclohexvl)acetyl]pipera?ine-1-carboxylate was prepared from (3-benzyloxyphenyl)(4-hydroxycyclohexyl)aceticacid (Reference Example 1-nn) and terf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 509 ([M+H]+); HRMS: calcd for CacH-oN^Os, 508.2937; found (ESI), 509.2997. [0336] In an analogous manner to Example 1, step 2 1-{1-[3-(bonzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride was prepared from terf-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-(1-(3-chlorophenyl)-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride 125 WO 2005/037809 PCT/US2004/033990 [0337] In an analogous manner to Example 1, step 1 2-(3-chlorophenyl)-2-(1 -.hvdroxvcvclohexyl]-A/-[4-(trifluoromethyl)benzyl]acetamide was prepared from (3-chlorophenyl)(1-hydroxycyc!ohexyl)acetic acid (Reference Example 1-a) and 4-trifluoromethylbenzylamine. MS (ESI) m/z 426/428 ([M+H]+). [0338] In an analogous manner to Example 1, step 2 1-(1-(3-chlorophenyl)-2-{[4-(trifluorornethyl)benzyl]amino}ethyl)cyclohexanol hydrochloride was prepared from 2-(3-chlorophenyl)-2-(1 -hydroxycycIohexyl)-A/-[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 [0339] In an analogous manner to Example 1, step 1 1 -[2-morpholin-4-vl-1 -(2-naphthyl)-2-oxoethyl]cvclohexanol was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and morpholine. HRMS: calcdfor C22H27NO3, 353.1991; found (ESI_FT), 354.20523. [0340] In an analogous manner to Example 1, step 2 1-[2-morphoIin-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 (ESLFT), 340.2256. Example 107: 2-[1 -(3-bromophenyl)-2-piperazin-1 -ylethyl]adamantan-2-ol dihydrochloride 126 WO 2005/037809 PCT/US2004/033990 [0341] In an analogous manner to Example 1, step 1 fe/t-butyl 4-f(3-bromophenyr)(2-hvdroxv-2-adamantyl)acetyl]piperazine-1-carboxvlate was prepared from (3-bromophenyl)(2-hydroxy-2-adamantyI)acetic acid (Reference Example 1-oo) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 533/535 ([M+H]+). [0342] In an analogous manner to Example 1, step 2 2-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]adamantan-2-ol dihydrochloride was prepared from fe/f-butyl 4-[(3-bromophenyl)(2-hydroxy-2-adamantyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 419/421 ([M+H]+); HRMS: calcd for C22H3iBrN2O • 2.00 HCI, 490.1153; found (ESI), 419.1682. Example 108: 1 -[1 -[3-(benzyloxy)phenyl]-2-(4-methylpiperazin-1 -yi)ethyl]cyclohexanol dihydrochloride [0343] 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-(benzy!oxy)phenyl]-2-piperazin-1-yIethyI}cyclohexanol (see Example 104). HRMS: calcd for C26H36N2O2 ' 2.00 HCI, 480.2310; found (ESI), 409.2838. Example 109: 1-[2-morpho!in-4-yl-1-(2-naphthyl)ethyl]cyclobutanol hydrochloride 127 WO 2005/037809 PCT/US2004/033990 [0344] In an analogous manner to Example 1, step 1 1 -r2-morpholin-4-vl-1 -(2-naphthvl)-2-oxoethyl]cvclobutanol was prepared from (1-hydroxycyclobutyl)(2-naphthyl)acetic acid (Reference Example 1-c) and morpholine. HRMS: calcd for P20H23NO3, 325.1678; found (ESLFT), 326.17435. [0345] In an analogous manner to Example 1, step 2 1 -r2-morpholin-4-yl-1 -(2-naphthyl)ethyl]cyclobutanol hydrochloride was prepared from 1-[2-morpholin-4-yl-1-(2-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-yIethyl]tetrahydro-2H-pyran-4-ol dihydrochloride [0346] In an analogous manner to Example 1, step 1 fetf-butyl 4-f(3-bromo-4-methoxvphenvl)(4-hydroxytetrahvdro-2AV-pvran-4-vl)acetyl]piperazine-1-carboxylate was prepared from (3-bromo-4-methoxyphenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetic acid (Reference Example 1-pp) and fe/t-butyl 1-piperazinecarboxylate. MS (ESI) m/z 513/515 ([M+H]+); HRMS: calcd for CaaHssBirNaOe, 512.1522; found (ESI), 513.16. [0347] In an analogous manner to Example 1, step 2 4-[1-(3-bromo-4-methoxyphenyl)- 2-piperazin-1-ylethyl]tetrahydro-2/-/-pyran-4-ol dihydrochloride was prepared from tert- Ibutyl 4-[(3-bromo-4-methoxyphenyl)(4-hydroxytetrahydro-2W-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. 128 WO 2005/037809 PCT/US2004/033990 Example 111: 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol dihydrochloride [0348] In an analogous manner to Example 1, step 1 /ert-buryl 4-[[3-(benzvloxv)phenvll(1-hydroxvcvclobutyl]acetyl]piperazine-1-carboxvlate was prepared from (3-benzy!oxyphenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-qq) and /erf-butyl 1-piperazinecarboxylate. MS (ESI) m/z481 ([M+H]+); HRMS: calcd for C28H36N2O5, 480.2624; found (ESI), 481.272. [0349] In an analogous manner to Example 1, step 2 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-ylethyl}cyclobutanol dihydrochloride was prepared from terf-butyl 4-[[3-(benzyloxy)phenyl](1-hydroxycyclobutyl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C23H3oN202 • 2.00 HCI, 438.1841; found (ESI), 367.2357. Example 112: 1-[1-(3,4-dichlorophenyl)-2-morpholin-4-ylethyl]cyclohexanol hydrochloride 129 WO 2005/037809 PCT/US2004/0JJ990 [0350] In an analogous manner to Example 1, step 1 1 -[ 1 -(3.4-dichlorophenyl)-2-morpholin-4-vl-2-oxoethyllcvclohexanol was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and morpholine. HRMS: calcd for CsH^CbNCb, 371.1055; found (ESI_FT), 372.11122. [0351] In an analogous manner to Example 1, step 2 1-[1-(3,4-dichlorophenyl)-2- morpholin-4-ylethyl]cyclohexanol hydrochloride was prepared from 1-[1T(3,4- dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]cyclohexanol. HRMS: calcd for C8H25CI2NO2 • HCI, 393.1029; found (ESI_FT), 358.13358. Example 113: 1-[2-[(4-fluorobenzyl)amino]-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride 10352] In an analogous, manner to Example 1, stop 1 A/-(4-fluorobenzyl)-2-(1 -hvdroxvcyclohexvl)-2-(2-naphthyl)acetamide was prepared from (1-hydroxycyclobuty!)(2-naphthyl)acetic acid (Reference Example 1-c) and 4-fluorolbenzylamine. MS (ESI) m/z 372 ([M+H-H2O]+). [0353] In an analogous manner to Example 1, step 2 1-[2-[(4-fluorobenzyl)amino]-1-(2-naphthyl)ethyl]cyc!ohexanol hydrochloride 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. 130 WO 2005/037809 PCT/US2004/033990 Example 114: 4-[1-(3,4-dichlorophenyl)-2-morpholin-4-ylethyl]-1-mothylpipericiin-4-ol dihydrochloride [0354] In an analogous manner (o Example 1, step 1 4-[1-(3,4-dichlorophenvO-2-morpho)in-4-vl-2-oxoethylH-rnethv)piperidin-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 CieH24CI2N2O3, 386.1164; found (ESI_FT), 387.12304. [0355] In an analogous manner to Example 1, step 2 4-[1-(3,4-dichlorophenyl)-2-morpholin-4-ylethyl]-1-methylpiperidin-4-ol dihydrochlorido was prepared from 4-[1-(3,4-dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]-1-meihylpiperidin-4-ol. HRMS: calcd for C18H26CI2N2O2 • 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 [0356] In an analogous manner to Example 24, 1-[1-[3-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyc!obutanol dihydrochloride was prepared from 1-{1-[3-(benzyloxy)phenyl]-2-piperazin-1-yIethyl}cyclobutanol (see Example 111). HRMS: calcd for C24H32N2O2 • 2.00 HCI, 452.1997; found (ESI), 381.2524. 131 WO 2005/037809 PC T/US2004/033990 Example 116: 4-[1-(3-bromophenyl)-2-morpholin-4-ylethyl]-1-methylpiperidin-4-ol dihydroeriioride [0357] In an analogous manner to Example 1, step 1 4-f1-(3-bromophenyl)-2-morpholin-4-yl-2-oxoethvl]-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 CisHssBrNzOg, 396.1049; found (ESI_FT), 397.11148. [0358] 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 Ci8H27BrN2O2 • HCI, 418.1023; found (ESI_FT), 383.13261. Example 117: 1 -(1 -(3-chlorophenyl)-2-(4-[(6-methoxv-2-naphthvl)methvllpiperazin-1 - yl)ethyl)cyclohexanol dihydrochloride [0359] A solution of 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) (200 mg, 0.62 mmol) and 6-methoxy-2-napthaldehyde (173 mg, 0.93 mmol) in dichloroethane (4 mL) was treated with sodium trisacetoxyborohydride (195 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 yield 194 mg (64%) 1-(1-(3- 132 WO 2005/037809 PCT/US2004/033990 chlorophenyl')-2-(4-f(6-methoxv-2-naphthyl]mcthvllpiperazin-1-vl)ethvl)cvclohexanol dihydroc'hloride as a white solid. MS (ESI) m/z 493/495 ([M+H]+); HRMS: calcd for C30H37CIN2O2 2.00 HCI, 564.2077; found (ESI_FT), 493.2632. Example 118: 1-(1-(3-chlorophenvl)-2-f4-(cvclopropylmethvl)piperazin-1-yllethyl)cyclohexanol dihydrochloridG [0360] In an analogous manner to Example 117, 1-(1-(3-chlorophenvl)-2-f4-(cyclopropvlmethyl)piperazin-1-vllethvl)cvclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-y!ethyl]cyclohexanol (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-(1-(3-chlorophenvl)-2-[4-(cvclohex-3-en-1-vlmethyl)piperazin-1- yllethyllcyclohexanol dihydrochloride [0361] In an analogous manner to Example 117, 1-(1-(3-chlorophenyl)-2-f4-(cyclohex-3-en-1-vlmethvl)piperazin-1-yl]ethyl)cvclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-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. 133 WO 2005/037809 PCT/US2004/033990 Example 120: 6-((4-[2-(3-chlorophenyl)-2-(1 -hvdroxvcvclohexvl)ethvl]piperazin-1 -vl)methyl)tetrahvdro-2H-pvran-2-ol dihydrochloride [0362] In an analogous manner to Example 117, 6-((4-[2-(3-chlorophenvl)-2-(1 -hvdroxvcvclohexvl)ethvl|piperazin-1-yl)methyl)tetrahvdro-2rt-pyran-2-ol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-y!ethyl]cyclohexanol (see Example 1) and 3,4-dihydro-2H-pyran-2-carboxaldehyde. HRMS: calcd for C24H37CIN2O3 • 2.00 HCI, 508.2026; found (ESI), 419.2455. Example 121: 1-(1-(3-chlorophenvl)-2-f4-(3-phenvlbutyl)piperazin-1-yl]ethyDcyclohexanol dihydrochloride [0363] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-[4-(3-phenylbutyl)piperazin-1 -vllethyllcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 3-phenylbutyraldehyde. MS (ESI) m/z455/457 ([M+H]*); HRMS: calcd for C28H39CIN2O • 2.00 HCI, 526.2284; found (ESI_FT), 455.28235. Example 122: 1-(1-(3-chlorophenvl)-2-f4-(2-phenvlGthyl)piperazin-1-yllethyl)cyclohexanol dihydrochloride 134 WO 2005/037809 PCT/US2O04/03399O [0364] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-f4-(2-phenylethyl)piperazin-1 -vliethyQcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and phenylacetaldehyde. MS (ESI) m/z427/429 ([M+H]+); HRMS: calcd for C26H35CIN2O ¦ 2.00 HCI, 498.1971; found (ESI), 427.2505. Example 123: 1-(1-(3-chlorophenvl)-2-[4-(3-phenoxvbenzyl)piperazin-1-yliethyDcvclohexanol dihydrochloride :0365] In an analogous manner to Example 117, 1-(1-(3-chlorophenyl)-2-f4-(3-phenoxvbenzvl)piperazin-1-yl]ethyl|cvclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohoxanol (see Example 1) and 3-phenoxybenzaldehyde. MS (ESI) m/z505/507 QM+H]+); HRMS: calcd for C31H37CIN2O2 2.00 HCI, 576.2077; found (ESI_FT), 505.26266. 135 Example 124: 1 -(1 -(3-chlorophenyl)-2-f4-(2-naphthylmethyl)piperazin-1 -yliethyllcyclohoxanol dihvdrochloride WO 2005/037809 PCT/US2004/033990 [0366] In an analogous manner to Example 117, 1 -{1 -(3-chlorophenyl)-2-[4-(2-naphthyimethvl)piperazin-1-vllethvl)cvclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophenyl)-2-pipGrazin-1-ylethyl]cyclohexanol (see Example 1) and 2-napthaldehyde. MS (ESI) m/z 463/465 ([M+H]+); HRMS: calcd for C29H35CIN2O • 2.00 HCI, 534.1971; found (ESI), 463.2499. Example 125: 1 -(1 -(3-chlorophenvO-244-(3-furvlmethvl)piperazin-1 -ynethyQcyclohexanol dihvdrochloride [0367] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-[4-(3-furylmethyl)piperazin-1 -yliethyDcyclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-y!ethyl]cyclohexanol (see Example 1) and 3-furaldehyde. 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-(cyclohexvlmethvl)piperazin-1 -yl]ethvljcyclohexanol dihvdrochloride [0368] In an analogous manner to Example 117, 1-{1-(3-chlorophenyl)-2-[4-(cvclohexvlmethvl)piperazin-1-vl1ethyl)cvclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophcnyl)-2-piperazin-1-ylethyl]cyclohexanol (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. 136 WO 2005/037809 PCT/US2004/033990 Example 127: 1 -(1 -(3-chlorophenyl)-2-[4-(quinolin-4-vlmethvl)piperazin-1 -yl]ethyl}cyclohexanol dihvdrochloride [0369] In an analogous manner to Example 117, 1-(H3-chlorophenyl)-2-f4-(quinolin-4-ylmethyl)piperazin-1 -yliethyl)cyclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 4-quinolinecarboxaldehyde. MS (ESI) m/z464/466 ([M+H]+); HRMS: calcd for C28H34CIN3O • 3.00 HCI, 571.1691; found (ESI_FT), 464.24693. Example 128: 1-(1-(3-chlorophenvl)-2-(4-r(5-ethvl-2-furv0mGthvl1piperazin-1- yl)ethyl)cvclohexanol dihvdrochloride [0370] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-(4-f(5-ethvl-2-furvl)methvHpiperazin-1 -yl)ethvl)cyclohexanol dihydrochlorido was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexano! (see Example 1) and 5-ethyl-2-f jraldehyde. MS (ESI) m/z [M+H]+ (431/433); HRMS: calcd for CO5H35CIN2O2 • 2.00 HCI, 502.1921; found (ESI), 431.2454. Example 129: 1 -(1 -(3-chlorophenvl)-2-[4-(2-phenvlpropyl)p)perazin-1 -yllethvUcyclohexanol dihvdrochloride 137 WO 2005/037809 PCT/US2004/033990 [0371] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenvl)-2-f4-(2-phenvlpropvl)piperazin-1-vl1ethvllcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 2-phenylpropionaldehyde. 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-f4-(1 -benzofuran-2-ylmethyl)piperazin-1 -yll-1 -(3-chlorophenyl)ethylicyclohexanol dihydrochloride [0372] In an analogous manner to Example 117, 1 -[2-f4-( 1 -benzofuran-2-ylmethyQpiperazin-1 -yli-1 -(3-chlorophenyl)ethvllcvclohexanol dihydrochloride was orepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and benzo[B]furan-2-carboxaldehyde. MS (ESI) m/z [M+H]+ (453/455); HRMS: calcd for C27H3SCIN2O2 • 2.00 HCI, 524.1764; found (ESI), 453.2296. 138 Example 131: 1-[2-(4-f4-(benzyloxy)bcnzyllpiperazin-1-yl)-1-(3-chloroohenyl)ethvllcyclohexanol dihydrochloride WO 2003/037809 PCT/US2004/033990 [0373] In an analogous manner to Example 117, 1-[2-(4-[4- (benzyloxv)benzylipiperazin-i -yl)-1 -O-chlorophenyl)ethyllcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 4-benzyloxybenzaldehyde. 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-(1-(3-chloroph.envl)-2-[4-(4-phenoxvbenzvl)piperazin-1-ynethyllcyclohexanol dihydrochloride [0374] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-[4-(4-phenoxybenzyl)piperazin-1 -yl]ethyllcyclohexanol 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]4); HRMS: calcd forC3iH37CIN2O2 2.00 HCI, 576.2077; found (ESI_FT), 505.26224. Example 133: 1 -(1 -(3-chlorophenvl)-2-f4-(pvridin-4-ylmethyl)piperazin-1 -vliethyDcyclohexanol dihydrochloride [0375] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenvl)-2-[4-(pyridin-4-vlmethvl)piperazin-1 -yliethyDcvclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 4-pyridinecarboxaldehyde. MS (ESI) m/z [M+H]+ (414/416); HRMS: calcd for C24H32CIN3O • 2.00 HCI, 485.1767; found (ESI), 414.2307. 139 WO 2005/037809 PCT/US2004/033990 Example 134 : 1-(1-(3-chlorophenyl]-2-r4-(pyridin-3-vlmethvl)piperazin-1-yllethyl)cvclohexanol dihydrochloride [0376] In an analogous manner to Example 117, 1-{1-(3-chlorophcnyl)-2-[4-(pyridin-3-ylmethyl)piperazin-1-yl]ethyl}cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-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-vl)-2-piperazin-1-vlethvl1cvclohexanol dihydrochloride [0377] Step 1: In an analogous manner to Example 1, step 1 ter/-butyl 4-[(3-bromophenyl)(1-hvdroxvcvclohexyl)acetvllpiperazine-1-carboxylate was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and /erf-butyl 1-piperazinecarboxylate. HRMS: calcd for C23H33BrN2C>4, 480.1624; found (ESI_FT), 481.16857. [0378] Step 2: A solution of /erf-butyl 4-[(3-bromophenyl)(1- nydroxycyclohexyl)acetyl]piperazine-1-carboxylate (2.12 g, 4.40 mmol) in dry 140 WO 2005/037809 PCT/US2004/033990 tetrahyckofuran (10 ml_) under nitrogen was treated dropwise with a solution of borane (1.0 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 (15 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 yield 2.02 g (98%) tert-butyl 4-[2-(3-brornophenvl)-2-(1-hydroxvcvclohexyl)ethyl]piperazine-1-carboxylate as a white powder. MS (ESI) m/z 467/469 ([M+H]+); HRMS: calcd for C^HssBr^Oa, 466.1831; found (ESI), 467.1899; Anal. Calcd for C^HasBrt^Oa: C, 59.10; H, 7.55; N, 5.99. Found: C, 59.14; H, 7.72; N, 5.77. [0379] Step 3: A mixture of tert-butyl 4-[2-(3-bromophenyl)-2-(1- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (0.72 g, 1.55 mmol) and tetrakis(tripheny!phosphine)palladium (37 mg, 0.032 mmol, 10 mo!%) in 1,2-dimethoxyethane (30 mL) was stirred for 10 min at room temperature. To this mixture was added sequentially 3,4-dichlorophenyl 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 yield 0.55 g (67%) of tert-butvl 4-[2-(3'.4'-dichloro-biphenyl-3-yl)-2-(1 -hydroxvcyclohexyl)ethylipiperazine-1 -carboxylate as a foam, which was used as such in the next step. ,0380] Step 4: tert-butyl 4-[2-(3',4'-dichloro-biphenyl-3-yl)-2-(1- nydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (0.39 g 0.73 mmol) was dissolved in diethyl ether (15 mL) then a 2N ethereal solution of hydrochloric acid (10 mL) was added. Methanol (approximately 1 mL) was then added until the resulting precipitate 141 WO 2005/037809 PCT/US2004/033990 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 yield 0.28 g (81%) of 1 -f 1 -(3'.4'-dichloro-1,1 '-biphenvl-3-vl)-2-piperazin-1 -vlethvHcvclohexanol dihvdrochloride as a white solid. MS (ESI) m/z 433/435/437 ((M+H]+); HRMS: calcd for C24H3oN2OCl2 • 2.00 HCI, 433.1813; found (ESI), 433.1813 Example 136: 1 -f 1 -(1.1 '-biphenyl-3-vO-2-piperazin-1 -vlethvlicyclohexanol dihvdrochloride [0381] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(1.1'-biphenyl-3- yl)-2-(1 -hydroxvcvclohexvOethvlipiperazine-i -carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 135, step 2) and phenyl boronic acid. [0382] In an analogous manner to Example 135, step 4 1 -[1 -(1,1 '-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol dihvdrochloride was prepared from tort-butyl 4-[2-(1,1'-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-f1-(4'-chloro-1,1'-biphenvl-3-vl)-2-piperazin-1-ylethyl]cyclohexanol 142 dihvdrochloride WO 2005/037809 PCT/US2OO4/03399O [0387] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'-chloro-biphenvl-3-vl)-2-(1-hvdroxvcvclohexyl)ethyl]piperazine-1-carboxvlate 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. [0388] In an analogous manner to Example 135, step 4 1 -[ 1 -(3'-ch)oro-1,1 '-biphenyl-3- yl)-2-piperazin-1-ylethyl]cyclohexanol dihyorochloride was prepared from tert-butyl 4-[2- (3'-chloro-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 399/401 ([M+H]+); HRMS: calcd for C2.iH3iCIN2O • 2.00 HCI, 470.1658; found (ESI), 399.2183. Example 140: 1-[1-(2'-fluoro-1,1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclohexanol maleate [0389] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(2'-fluoro-biphenvl-3-vl)-2-(1-hydroxycvclohexvl)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 2-florophenyl boronic acid. [3390] In an analogous manner to Example 135, step 4 1 -f 1 -(2'-fluoro-1.1 '-biphenvl-3- yl)-2-piperazin-1 -vlethylicyclohexanol 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 yield 1-f1-(2'-fluoro- 144 WO 2005/037S09 PCT/US2OO4/033990 1.i'-bipiyenvl-3-vl)-2-pipera?in-1-vlethyl]cvclohexanol maleate as a colorless solid. MS (ESI) m/z 383 ([M+HJ+); 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-ri-(2.5-dichlorothien-3-vl)-2-pipGrazine-1-vlethyl]cyclohexanol dihydrochloride [0391] Step 1: A solution of 3-thiophene acetic acid (1.42 g, 10.0 mmol) in acetic acid (10 ml_) was treated with N-chlorosuccinimide (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]-). [0392] Step 2: In an analogous manner to Example 1, step 1 tert-butyl 4-[(2.5-dichlorothien-3-vl)acetyl]piperazine-1-carboxvlate was prepared from 2,5-dichlorothiophene-3-acetic acid and tert-butyl 1-piperazinecarboxylate. The product was crystallized from ethyl acetate: hexane to yield a colorless solid. [0393] Step 3: A solution of diisopropyl amine (0.80 ml_, 5.6 mmol) in dry tetrahydrofuran (10mt_) under nitrogen was cooled to -78 °C and treated dropwise with a solution of n-butyllithium (1.6 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- 145 WO 2005/O37809 PCT/US2004/033990 carboxylate (1.7 g, 4.5 mmol) in tetrahydrofuran (10 ml_). After the addition was complete, the solution was stirred for 0.5 hr at -78 °C whereupon cyclohexanone (0.57 mL, 5.6 mmol) 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 (1x10 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 -hydroxvcvclohexyl)acetvllpiperazine-1-carboxvlate as a white foam. MS (ESI) m/z 477/479/481 ([M+H]), HRMS: calcd for C^oC^CS, 476.1303; found (ESI), 477.1362. [0394] Step 4: In an analogous manner to Example 135, Step 2 tert-butvl 4-[2-(2.5-dichlorothien-3-vl)-2-(1-hvdroxvcvclohexyl]ethvl1piperazine-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 C2iH3?Cl2N2O3S, 462.1511; found (ESI), 463.1594. [0395] Step 5: In an analogous manner to Example 135, step 4 1 -[1 -(2.5-dichlorothien-3-vl)-2-piperazine-1-vlethvl]cvclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(2,5-dichlorothien-3-yl)-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 C,6H24CI2N2OS ¦ 2.00 HCI, 434.0520; found (ESI), 363.1035. Example 142: 1-f1-(5-chlorothien-2-yl]-2-piperazin-1-vlethyllcvclohGxanol 146 dihvdrochloride [0398] In an analoguous manner to Example 1, step 2 1 -[1 -(5-chlorothien-2-yl)-2-piperazin-i-vlethvllcyclohexanol 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 Ci6H25CIN2OS • 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-vl)-2-piperazin-1-ylethvl1cvclohexanol dihydrochloride [0399] 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) [0400] In an analogous manner to Example 1, step 1, tert-butyl 4-f(5-bromothien-2-vl)(1-hydroxvcvclohexyl)acetyl1piperazine-1-carboxvlate 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]+ 147 WO 2005/037809 PCT/US2004/033990 [0396] -in an analogous manner to Example 141, step 1 (5-chlorothien-3-yl)acetic acid wasprepared from 2-thiophene acetic acid and N-chlorosuccinimide. (This acid was used in Reference Example 1-rr) MS (ES) m/z 175.0 ([M-H]-) [0397] In an analogous manner to Example 1, step 1 tert-butyl 4-[(5-chlorothien-2-vl)(1-hvdroxvcvclohexyl)acetvHpiperazine-1-carboxvlate was prepared from (5-chlorothien-2-yl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-rr) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 443/445 ([M+H]+) [0398] In an analoguous manner to Example 1, step 2 1 -f 1 -(5-chlorothien-2-yl)-2-piperazin-1-ylethyl]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 deH^CINoOS • 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-f1-(5-bromothien-2-vl)-2-piperazin-1-vlethyllcvclohexanol dihydrochloride [0399] 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) [0400] In an analogous manner to Example 1, step 1, tert-butyl 4-f(5-bromothien-2-yl)(1 -hydroxvcvclohexvl)acetyl]piperazine-1 -carboxylate was prepared from (5-bromothien-2-y!)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-ss) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 487/489 ([M+H]+ 147 WO 2005/037S09 PCI7US2004/033990 [0401] In an analogous manner to Example 1, step 2, 1 -f1 -(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, 5.60. Example 144: 1-f1-(5-chlorothien-3-vl)-2-piperazin-1-ylethyncvclohexanol dihydrochloride [0402] In an analogous manner to Example 1, step 1 tert-butyl 4-[(5-chlorothien-3-yOacetylipiperazine-i-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 [0403] In an analogous manner to Example 141, step 3, tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1 -hydroxycyclohexypethvlipiperazine-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 CaiHfeaCINzOsS, 428.1900; found (ESI), 429.1973. [0404] In an analogous manner to Example 135, step 2, tert-butyl 4-[2-(5-chlorothien-3-vl)-2-(1-hvdroxvcvclohexvl)ethyllpiperazine-1-carboxylate was prepared from tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohoxyl)ethyl]piperazine-1-carboxylate. [0405] In an analogous manner to Example 135, step 4 1 -f 1 -(5-chlorothien-3-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 2 Monyurzi, R.; Ubassi, G.; Pmza, M.; Pifferi, G. Synthesis of new a-hydra7inoarylacetjc acids and derivatives. Farmaco, Ed^ione Sciertifxa (1976), 3!(8), 5-19-60 148 WO 2005/037809 PCT/US2004/033990 329/33.1 ([M+H]1); HRMS: calcd for C16H25C1N2OS ' 2.00 HCI, 400.0910; found (ESI), 329.1444. Example 145: 1-[2-(4-aminopiperidin-1-yl)-1-(5-chlorothien-3-y))ethyl]cydohexanol dihydrochloride [0406] In an analogous manner to Example 1, step 1 tert-butylf1-[2-(5-chloro-thiophen-3-yl)-acetyl]-piperidin-4-yl)-carbamate was prepared from 5-chlorothiophene-3-acetic acid and 4-N-boc-aminopiperidine. [0407] In an analogous manner to Example 141, step 3, tert-butyl{1 -[2-(5-chloro- thiophen-3-yl)(1-hydroxycyclohexyl)acetvl]-piperidin-4-yl}-carbamate was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)-acetyl]-piperidin-4-yl}-carbamate and cyclohexanone. [0408] In an analogous manner to Example 135, step 2, tert-butyl(1 -[2-(5-chloro-thiophen-3-vl)(1-hvdroxycvclohexyl)ethvl]-piperidin-4-yl}-carbamate was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)(1-hydroxycyclohexyl)acetyl]-piperidin-4-y!}-carbamate.) [0409] In an analogous manner to Example 135, step 4 1 -[2-(4-aminopiperidin-1 -yQ-1 -(5-chlorothien-3-vl)ethyncyclohexanol dihydrochloride was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)(1 -hydroxycyclohexy!)ethyl)-piperidin-4-yi}"Carbamate. MS (ESI) m/z 343/345 ([M+H]+); HRMS: calcd for C17H27CIN2OS ¦ 2.00 HCI, 414.1066; found (ESI), 343.1594. Example 146: 1 -[1 -(1 -benzothien-3-y()-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride 149 WO 2005/037809 PCT/US2004/033990 [0410] In an analogous manner to Example 1, step 1 t-butyl 4-M-f1-(1-benzothien-3-yl)(1 -hydroxycyclohexvOacetyllpiperazine-i -carboxylate was prepared from 1-benzothien-3-yl(1-hydroxycyclohexyl)acetic acid (Reference Example 1-tt) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 487/489 ([M+H]+ [0411] In an analoguous manner to Example 1, step 2 1 -f1 -(1 -benzothien-3-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from t-butyl 4-[1-[1-(1-benzothien-3-yl)(1-hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z [M+H]+ (345); HRMS: calcd for C20H26N2OS • 2.00 HCI, 416.1456; found (ESI), 345.2024 Example 147: 1-[1-(3'.4'-difluoro-1.1'-biphenyl-3-vl)-2-piperazin-1-ylethyl]cvclohexanol dihydrochloride [0412] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3',4'-difluoro-biphenvl-3-vO-2-(1-hvdroxvcyclohexvl)ethvHpiperazinc-1-carboxvlate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (see Example 135, step 2) and 3,4-difluorophenyl boronic acid. .'0413] In an analogous manner to Example 135, step 4 1-[1-(3',4'-difluoro-1.1'-biphenvl-3-yl)-2-piperazin-1-vlethvl1cyclohexanol dihvdrochloride was prepared from lert-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 C24H30[2N2O ¦ 2.00 HCI, 472.1860; found (ESI), 401.2378 150 WO 2005/037809 PCT/US2004/033990 Example 148: 1-[1-(3',4'-dichloro-1,1'-biphenyl-2-vl)-2-piperazin-1-vlethvl]cvclohexanol dihydrochloride [0414] In an analogous manner to Example 1, step 1 tert-butyl 4-f(2-bromophenyl)(1-hydroxvcvclohexyDacetvllpiperazine-i-carboxylate was prepared from (2-bromophenyl)(1-hydroxycyclohcxyl)acetic acid (Reference Example 1-uu) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 481/483 ([M+H]+); HRMS: calcd for C23H33BrN2Oa, 480.1624; found (ESI), 481.1689 [0415] In an analoguous manner to Example 135, step 2, tert-butyl 4-[2-(2- bromophenyl)-2-(1-hvdroxvcvclohexyl)ethvl]piperazine-1-carboxvlate was prepared from tert-butyl 4-[(2-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylatc. MS (ESI) m/z 467/469 ([M+H]+); HRMS: calcd for C23H35BrN2O3, 466.1831; found (ESI), 467.1895; [0416] In an analogous manner to Example 135, step 3 tert-butyl 4-[3'4'dichloro-1.1'-biphenvl-2-vl)-2-(1-hvdroxvcvclohexvl)ethynpiporazine-1-carboxvlate was prepared from tert-butyl 4-[2-(2-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylato and 3,4-dichloro phenyl boronic acid. [0417] In an analogous manner to Example 135, step 4 1-[1-(3'.4'-dichloro-1,V-biphenyl-2-yl)-2-piperazin-1-y!ethyl]cyclohexanol 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 C24H3oCI2N20 • 2.00 HCI, 504.1269; found (ESI), 433.1797 151 WO 2005/037809 PCT/US2004/033990 -Example 149: 1 -f 1 -(1,1 '-biphenvl-2-yl)-2-piperazin-1 -ylethyllcvclohexanol dihydrochloride [0418] In an analogous manner to Example 135, step 3 tert-butyl 4-f 1,1 '-biphenyl-2-yQ-2-(1-hydroxvcyclohexvl)ethyllpiperazine-1-carboxvlate 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. [0419] In an analogous manner to Example 135, step 4 1 -[1 -(1,1 '-biphenyl-2-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[1,1'-biphenyl-2-yl)-2-(1-hydroxycyclohoxyl)cthyl]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 '-bipheny!-2-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0420] In an analogous manner to Example 135, step 3 tert-butyl 4-f3'-chloro-1.1'-biphenvl-2-vl)-2-(1-hvdroxycyclohexvl)ethvl[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-ch!oro phenyl boronic acid. 152 WO 2005/037809 PCT/US2004/033990 [0421] In an analogous manner to Example 135, step 4 1-f1-(3'-chloro-1,1'-biphenyl-2-yl)-2-piperazin-1 -vlethvlicvclohexanol dihvdrochlorido was prepared from tort-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 C2/.H3iCIN2O ¦ 2.00 HCI, 470.1658; found (ESI), 399.2211 Example 151:1 -{1 -[2-(1,3-benzodioxol-5-yl)phenyl]-2-piperazin-1 -ylethyljcyclohexanol dihydrochloride [0422] In an analogous manner to Example 135, step 3 tort-butyl 4-f1-(1.3- benzodioxol-5-vlphenvl)-2-(1-hydroxvcvclohexvl)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. [0423] In an analogous manner to Example 135, step 4 1 -(1 -[2-(1.3-benzodioxol-5- yl)phenyl1-2-piperazin-1 -ylethyllcyclohexanol dihydrochloride was prepared from tert- butyl 4-[1-(1,3-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-aminopiperid'm-1 -yl)-1 -(3'.4'-dichloro-1.1 '-biphenyl-3-yl)ethyncyclohexanol dihydrochloride 153 WO 2005/037809 PCT/US2OO4/033990 [0424] In an analogous manner to Example 135, step 3 tert-butyl (1-f(3'.4'-dichloro-1.1'-biphenvl-3-vl)f1-hvdroxvcvclohexyl]acetynpiperidin-4-vl)carbamato was prepared from_ferf-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 C30H38CI2N2O4, 560.2209; found (ESI), 561.2263 [0425] In an analogous manner to Example 135, step 2 tort-butyl (1 -[2-(3'.4'-dichloro-1.1'-biphenvl-3-vl)-2-(1-hvdroxvcyclohexvl)ethyllpiperidin-4-vl)carbamate was prepared from tert-butyl {1-[(3',4'-dichloro-1,1'-biphenyl-3-yl)(1-hydroxycyclohexyl)acetyl]piporidin-4-yl}carbamate. MS (ES) m/z 547.3 ([M+HJ+); HRMS: calcd for C30H40CI2N2O3, 546.2416; found (ESI), 547.2473. [0426] In an analogous manner to Example 135, step 3 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3',4'-dichloro-1.1 '-biphenyl-3-vl)ethvllcvclohexanol 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 C2bH32CI2N2O • 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 [0427] In an analogous manner to Example 1, step 1 terf-butyl 4-f(3-bromophenyl)(1-hydroxvcvclobutyDacetvlipiperazine-i -carboxylate was prepared (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and ter/-butyl 1- 154 WO 2005/037809 PCT/US2004/033990 piperazinecarboxylate. HRMS: calcd forC21H29BrN2O4, 452.1311; found (ESI_FT), 453.13746. [0428] In an analogous manner to Example 135, step 2 terf-butvl 4-[2-(3-bromophenvl)-2-(1-hvdroxvcvclobutvl)ethvi|piperazine-1-carboxvlate was prepared from tert-bu\y\ 4-[(3-bromophenyl)(1 -hydroxycyclobutyl)acetyl]piperazine-1 -carboxylate and 3,4-dichloro phenyl boronic acid. [0429] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'.4'-dichloro-biphenvl-3-vl)-2-(1-hvdroxvcvclobutvl)ethvl]pipera7.ine-1-carboxvlate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1 -hydroxycyclobutyl)ethyl]piperazine-1 -carboxylate and 3,4-dichloro phenyl boronic acid. [0430] In an analogous manner to Example 135, step 4 1-M-(3'.4'-dichtoro-1.1'-biphenyl-3-yl)-2-piperazin-1-vlethvHcvclobutanol 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-f1-(1-methyl-1 H-indol-3-yl)-2-piperazin-1-vlethvl]cyclohexanol dihydrochloride [0431] In an analogous manner to Example 1, step 1 tert-butyl 4-R1- hydroxycyclohexyl)d -methyl-1 H-indol-3-yl)acetynpiperazine-1 -carboxylate was orepared from (1-methyl-1 H-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 CssHs/NsO*. 455.2784; found (ESI_FT), 456.28501. 155 WO 2005/037809 PCT/US2004/033990 [0432] . In an analogous manner to Example 1, step 2 1-M-(1-methvl-1H-inclol-3-vl)-2-pipera2ifl-1 -ylethvlicyclohexanol dihvdrochloride was prepared from tert-butyl 4-[(1-hydroxycyclohexyl)(1 -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-f1-(1H-indol-3-vl)-2-piperazin-1-vlethvl1cyclohexanol dihydrochloride [0433] In an analogous manner to Example 1, step 1 tert-butyl 4-[(1- hydroxycyclohexvlH 1 -(tert-butvl-dimethyl-silanyl)-1 H-indol-3-yl)acetyHpiperazine-1 - carboxylate was prepared from (1-(tert-Butyl-dimethyl-silanyl)-1H-indol-3-yl) (1-hydroxycylclohexyl) acetic acid (Reference Example 1-yy) and tert-butyl 1-piperazinecarboxylate. [0434] In an analogous manner to Example 1, step 2 1 -f 1 -(1 /-/-indol-3-yl)-2-piperazin-1 -ylethvlicyclohexanol dihvdrochloride was prepared from tert-butyl 4-[(1-hydroxycyclohexyl)(1-(tort-butyl-dimethyl-silanyl)-1H-indol-3-yl)acGtyl]piperazine-1-carboxylate. MS (ESI) m/z 328 ([M+H]+); HRMS: calcd for C2oH29N30 ' 2.00 HCI, 399.1844; found (ESI_FT), 328.23696 Example 156: 1 -f 1 -[2-chlorothien-3-yl)-2-piperazin-1 -ylethyllcyclohexanol 156 dihvdrochloride WO 2005/037809 PCT/US2004/033990 [0435] ln an analogous manner to Example 141, step 1 (2-chlorothien-3-v0acetic 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-f(2-chlorothien-3-yl)acetvlipiperazine-1-carboxylato was prepared from (2-chlorothien-3-yl)acetic acid_and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 289.0 ([M+H-C4H8J+); HRMS: calcd for C15H21CIN2O3S, 344.0961; found (ESI), 345.1057. [0436] In an analogous manner to Example 141, step 3 tert-butyl 4-f(2-chlorothien-3-yl)(1-hydroxvcvclohexyl)acetyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[(2-chlorothien-3-yl)acetyl]piperazine-1 -carboxylate and cyclohexanone. [0437] In an anlogous manner to Example 135, step 2 tert-butyl 4-[2-(2-chlorothien-3-vl)-2-(1-hvdroxvcvclohoxvl)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+HJ+); HRMS: calcd for CaiHaaCINsOaS, 428.1900; found (ESI), 429.1967 [0438] In an analogous manner to Example 135, step 4 1 -f 1 -(2-chlorothien-3-yl)-2-piperazine-1 -vlethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(2-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 329/331 ([M+H]+); HRMS: calcd for C16H25C1N2OS • 2.00 HCI, 400.0910; found (ESI), 329.1442. Example 157: 1 -[1 -(1.1 '-biphenyl-4-yl)-2-piperazin-1 -vlethvlicyclohexanol 157 dihydrochloride WO 2005/037809 PCT/US2004/033990 [0439] In an analogous manner to Example 1, step 1 tert-butyl 4-[1,1 '-biphenyl-4-yin -hvdroxvcvclohexyl)acetvl1pipeiazine-1-carboxvlate was prepared from (1-hydroxycyclohexyl)(1,1'-biphenyl-4-yl)acGtic acid (Reference Example 1-zz) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 479 ([M+H]+); Anal. Calcd for C?DH38N2O.i: C, 72.77; H, 8.00; N, 5.85. Found: C, 72.69; H, 8.39; N, 5.80. [0440] In an analogous manner to Example 13, step 2 1 -f 1 -(1.1 '-biphenyl-4-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[1,1'-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-(1,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1-ylethyl]cyclohexanol dihydrochloride [0441] In an analogous manner to Example 24, 1 -M -(1.1 '-biphenvl-4-yl)-2-(4- methvlpipera?in-1-vlethyllcvclohexanol dihydrochloride was prepared from 1-[1-(1,1'-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-chlorothien-3-yl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol 158 dihydrochloride WO 2005/037S09 PCT/US2004/033990 [0442] In an analogous manner to Example 24, 1 -fl -(5-chlorothien-3-vl)-2-(4- mothylpiperazin-i -yl)ethvHcvclohexanol dihvdrochloride was prepared from 1-[1-(5-chlorothien-3-yl)-2-piperazin-1-ylothyl]cyclohexanol (see Example 144). MS (ES) m/z 343.2 ([M+H]+); HRMS: calcd for C17H2,'CIN2OS. 2.00 HCI, 414.1066; found (ESI), 343.1596. Example 160: 1-[1-(3-cyanophenyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0443] Step 1: A mixture of terf-butyl 4-[2-(3-bromophenyl)-2-(1- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 135, step 2) (467 mg, 1.00 mmol), zinc cyanide (141 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 (16 mg, 0.25 mmol) in anhydrous A/,A/-dimethy!formamide (5 mL) was heated at 125 °C under nitrogen until all starting material was consumed (5 h). After cooling to room temperature, water (10 mL) and a 2 N aqueous solution of ammonium hydroxide (5 mL) were added and the mixture was extracted with ethyl acetate (1 x 20 mL). The combined organic extracts were washed with brine (15 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 yield 345 mg (84%) /erf-butyl 4-[2-(3-cyanophenyl)-2-(1 -hydroxycvclohexyl)ethyllpiperazine-i-carboxvlate as a yellow solid. MS (ESI) m/z 414 {[M+H]*); HRMS: calcd for C^sNaCb, 413.2678; found (ESI), 414.2745. '0444] Step 2: In an analogous manner to Example 135, step 4, 1 -[1 -(3-cyanophenyl)-2-piperazin-1 -ylethylicyclohexanol dihvdrochloride was prepared from /erf-butyl 4-[2-(3-cyanophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 314 ([M+H]+); HRMS: calcd for C1SH27N3O • 2.00 HCI, 385.1688; found (ESI), 314.2225. 159 WO 2OO5/0378O9 PCT/US2004/033990 Example 161:1 -[1 -(3-cyanophenyl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol dihydrochloride [0445] In an analogous manner to Example 24, 1-M-(3-cyanophenyl)-2-(4- methylpiperazin-1 -yl)ethvlicvclohexanol 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 [0446] Step 1: A mixture of fort-butyl 4-[2-(3-bromophenyl)-2-(1- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 135, step 2) (141 mg, 0.300 mmol), tributyl(vinyl)tin (114 mg, 0.360 mmol, 1.2 equivalent), and tetrakis(triphenylphosphine)palladium (17 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 (1-2 h). Filtration through Celite® and purification via flash column chromatography (silica, gradient from 0% ethyl acetate/hexane to 10% ethyl acetate/hexane) yielded 111 mg (90%) tert-butyl 4-[2-(1- 160 WO 2005/037809 PCT/US2004/033990 hvdroxvcvclohexyl)^-O-vinvlphenyl]ethvllpiperazine-i-carboxvlate as a viscous colorless oil. MS (ES) m/z 415.4 ([M+H]*); HRMS: calcd for C25H38N22O3, 414.2882; found (ESI), 415.2966. [0447] Step 2: In an analogous manner to Example 135, step 4, 1-[2-piperazin-1-vl-1-(3-vinylphenvl)ethvl1cvclohexanol dihydrochloride was prepared from /erf-butyl 4-[2-(1-hydroxycyclohexyl)-2-(3-vinylphenyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 315 ([M+H]+); HRMS: calcd for C20H30N2O ¦ 2.00 HCI, 386.1892; found (ESI), 315.242. Example 163: 1-[2-piperazin-1-yl-1-(4-vinylphenyl)ethyl]cyclohexanol dihydrochloride [0448] In an analogous manner to Example 1, step 1 tert-butvl 4-r.(4-bromophenyl)(1-hvdroxvcvclohexvl)acetyl1piperazine-1-carboxvlate was prepared from (4-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-h) and /erf-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. [0449] In an analogous manner to Example 135, step 2, tert-butyl 4-[2-(4- bromophenvl)-2-(1-hvdroxvcyclohexv0ethvHpiperazine-1-carboxvlate was prepared from terf-butyl 4-[(4-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z467/469 ([M+H]4). [0450] In an analogous manner to Example 162, step 1, terf-butyl 4-I2-H- hvdroxycvclohexvl)-2-(4-vinvlphenyl)ethvllpiperazine-1-carboxvlate 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. 161 WO 2005/037809 PCT/US2004/033990 [0451] In an analogous manner to Example 135, step 4, 1 -[2-piperazin-1 -yl-1 -(4-vinvlphenvPethyl]cvclohexanol dihvdrochloride was prepared from rerf-butyl 4-[2-(1-hydroxycyclohexyl)-2-(4-vinylphenyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 315.3 ([M+H]+); HRMS: calcd forC20H3oN20 ¦ 2.00 HCI, 386.1892; found (ESI), 315.2424. Example 164: 1 -[2-piperazin-1 -yl-1 -(4-prop-1 -ynylphenyl)ethyl]cyclohexanol dihydrochloride [0452] In an analogous manner to Example 162, step 1, terf-butyl 4-[2-(1- hvdroxvcvclohexvl)-2-(4-prop-1-ynylphenvl')ethyl]piperazino-1-carboxylate was prepared from terf-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. [0453] In an analogous manner to Example 135, step 4, 1 -[2-piperazin-1 -yl-1 -(4-nrop-1 -vnylphenyl)ethylicyclohexanol dihvdrochloride was prepared from /erf-butyl 4-[2-(1-hydroxycyclohexyl)-2-(4-prop-1-ynylphenyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 327 ([M+H]+); HRMS: calcd for C21H30N2O • 2.00 HCI, 398.1892; found (ESI), 327.2425. Example 165: 1 -[1 -(2'-chloro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyl]cyc!ohexanol dihydrochloride 162 WO 2005/03780'; PCT/US2004/033990 [0454] Step 1: In an analogous manner to Example 135, step 3, tert-butvl 4-[2-(2'-.chloro-1,1'-biphenvl-4-vl)-2-(1-hvdroxvcvclohexyl)ethyl]piperazine-1-carboxvlate was prepared from tert-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using 2-chlorophenylboronic acid. MS (ESI) m/z499 ([M+H]+); HRMS: calcd for C29H39CIN2O3, 498.2649; found (ESI), 499.2745. [0455] Step 2: In an analogous manner to Example 135, step 4, 1-[1-(2'-chloro-1.1'-biphenvl-4-vl)-2-piperazin-1-ylethyl]cvclohexanol dihydrochloride was prepared from tarf-buty) 4-[2-(2'-chloro-1,1 '-biphenyl-4-yl)-2-(1 -hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 399 ([M+H]+); HRMS: calcd for C24H31CIN2O 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 [0456] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(3'-fluoro-1,1'-biphenvl-4-vl)-2-(1-hvdroxvcvclohexyl)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-fluorophenylboronic acid. MS (ESI) m/z 483 «M+H]+). 163 WO 2005/037809 PCT/US2004/033990 [0457] In an analogous manner to Example 135, step 4, 1-f1-(3'-fluoro-1,1'-biphenvl-4-yl)-2-piperazin-1 -vlethyljcyclohexanol dihydrochloride was prepared from /erf-butyl 4-[2-(3'-fluoro-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclohexy))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-f1-(3'-chloro-1,1'-biphenyl-4-vl)-2-piperazin-1-vlethvl1cyclohexanol dihydrochloride [0458] In an analogous manner to Example 135, step 3, /erf-butyl 4-r.2-(3'-chloro-1.V-biphenvl-4-vl)-2-(1-hvdroxvcvclohexvl)ethvlipiperazine-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+HD; HRMS: calcd for C29H39CIN2O3, 498.2649; found (ESI), 499.2738. [0459] In an analogous manner to Example 135, step 4, 1 -[1 -(3'-chloro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -vlethvlicvclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3'-chloro-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclohcxyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 399/401 ([M+H]); HRMS: calcd for C24H31CIN2O • 2.00 HCI, 470.1658; found (ESI), 399.2211. Example 168: 1 -f 1 -(3'-cyano-1.1 '-biphenvl-4-vl)-2-piperazin-1 -vlethvlicyclohexanol dihydrochloride ir>4 WO 2005/037809 PCT/US2004/033990 [0460] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(3'-cyano-1,1'-biphenvl-4-vl)-2-(1-hvdroxvcvclohexvl)ethvi1piperazine-1-carboxvlate was prepared from /erf-butyl 4-[2-(4-bromophenyl)-2-(1 -hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (see Example 163, step 2) using 3-cyanophenylboronic acid. MS (ESI) m/z 490 ([M+Hp. [0461] In an analogous manner to Example 135, step 4, 1 -[ 1 -(3'-cyano-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3'-cyano-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 390.3 ([M+Hp; HRMS: calcd for C25H31N3O • 2.00 HCI, 461.2001; found (ESI), ' 390.2532. Example 169: 1 -f 1 -(3'-nitro-1.1 '-biphenyI-4-yl)-2-piperazin-1 -ylethvlicyclohexanol dihydrochloride [0462] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(1- hvdroxvcvclohexvl)-2-(3'-nitro-1.1'-biphenvl-4-ynethyl]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-nitrophenylboronic acid. MS (ES) m/z 510.3 ([M+H]+).. WO 2005/037809 PCT/US2004/033990 [0463]' In an analogous manner to Example 135, step 4, 1-[1-(3'-nitro-1.1'-biphenvl-4-yl)-2-piperazin-1 -ylethyllcyclohexanol dihvdrochloride was prepared from /erf-butyl 4-[2-(1-hydroxycyclohexyl)-2-(3'-nitro-1,r-biphenyl-4-yl)Gthyl]piperazine-1-carboxylate. MS . (ES) m/z 410.3 ([M+HJ+); HRMS: calcd for C24H31N3O3 ' 2.00 HCI, 481.1899; found (ESI), 410.2452. Example 170: 1-f1-(3'-methoxv-1,1'-biphGnvl-4-yl]-2-piperazin-1-vlethyl]cyclohexanol dihvdrochloride [0464] In an analogous manner to Example 135, step 3, tert-butvl 4-[2-(1- hydroxvcvclohexvl)-2-(3'-methoxv-1.1'-biphenvl-4-vl)ethylipiperazine-1-carboxylate was prepared from tert-bu\y\ 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using 3-methoxyphenylboronic acid. MS (ES) m/z 495.4 ([M+H]+). [0465] In an analogous manner to Example 135, step 4, 1-[1-(3'-methoxv-1.l'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from terf-butyl 4-[2-(1-hydroxycyclohexyl)-2-(3'-rnethoxy-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'-(thfluoromethoxv)-1,1 '-biphenyl-4-yllethyllcvclohexanol dihydrochloride 166 WO 2005/037809 PCT/US2004/033990 [0466] In an analogous manner to Example 135, step 3, fert-butvl 4-(2-(1- hvdroxvcyclohexyl)-2-j3'-ftrif luoromethoxv)-1,1 '-biphenvl-4-vl1ethvl)piperazine-1 - carboxylate was prepared fe/f-butyl 4-[2-(4-bromophenyl)-2-(1- hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using 3-trifluoromethoxy phenylboronic acid. MS (ES) m/z 549.4 ([M+H]+). [0467] In an analogous manner to Example 135, step 4, 1 -(2-piperazin-1 -yl-1 -[3'-(trifluoromethoxy)-i ,1 '-biphenyl-4-ynethvl)cvclohexanol dihydrochloride was prepared from ferf-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 C25H31F3N2O2 ' 2.00 HCI, 520.1871; found (ESI), 449.2389. Example 172:1 -[1 -(4'-chloro-1,1'-biphenvl-4-vl)-2-piperazin-1-vlethyncyclohexanol dihydrochloride [0468] In an analogous manner to Example 135, step 3, tert-butyl 4-r2-(4'-chloro-1,1'-biphenyl-4-vl)-2-(1-hydroxvcyclohexyl]ethynpiperazine-1-carboxylate was prepared from fe/f-butyl 4-[2-(4-bromophenyl)-2-(1 -hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using 4-chlorophenylboronic acid. MS (ESI) m/z 499 ([M+H]+); HRMS: calcd for C29H39CIN2O3, 498.2649; found (ESI), 499.2718; 167 WO 2005/037809 PCT/US2004/033990 [0469] . In an analogous manner to Example 135, step 4, 1 -[1 -(4'-chloro-i .1 '-biphenvl-4-vl)-2-Diperazin-1-vlethvllcyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(4'-chloro-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. 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 '-biphenyl-4-yl)-2-piperazin-1 -ylethylicyclohexanol dihydrochloride [0470] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(3'.4'-dichloro-1,1'-biphenvl-4-vl)-2-(1-hvdroxvcvclohexvl)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 3,4-dichlorophenylboronic acid. MS m/z 533/535/537 ([M+H]+); HRMS: calcd for C29H38Cl2N2O3l 532.2259; found (ESI), 533.2329. [0471] In an analogous manner to Example 135, step 4, 1-[1-(3'.4'-dichloro-1.1'-biphenyl-4-yl)-2-piperazin-1 -ylethvUcyclohexanol dihydrochloride was prepared from tert-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 C24H3oCI2N20 2.00 HCI, 504.1269; found (ESI), 433.1793. Example 174: 1 -[2-piperazin-1 -vl-1 -(4-thien-3-vlphenynethyl]cvclohexanol dihydrochloride 168 WO 2005/037809 PCT/US2004/033990 [0472] In an analogous manner to Example 135, step 3, tert-butyl 4-[2-(1- hvdroxvcvclohexyl]-2-(4-thien-3-vlphenvl)ethvlloiperazine-1-carboxvlate was prepared from tert-buty! 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+H]+); HRMS: calcd for C27H38N2O3S, 470.2603; found (ESI), 471.2678. [0473] In an analogous manner to Example 135, step 4, 1 -[2-piperazin-1 -yl-1 -(4-thien-3-vlphenvl)ethyl]cvclohexanol dihydrochloride was prepared from terf-butyl 4-[2-(1-hydroxycyclohexyl)-2-(4-thien-3-ylphenyl)ethyl]piperazine-1-carboxylate. MS m/z 371 ([M+H]+); HRMS: calcd for C22H30N2OS • 2.00 HCI, 442.1612; found (ESI), 371.2144. Example 175: 1 -[1 -(2'-chloro-1,1 '-biphenyl-4-vl)-2-(4-methylpiperazin-1 -yl)ethyllcvclohexnnol dihydrochloride [0474] In an analogous manner to Example 24, 1 -[1 -(2'-chloro-1.1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyllcyclohexanol dihydrochloride was prepared from 1-[1-(2'-chloro-1,V-biphenyl-4-y))-2-piperazin-1-ylethyl]cyclohexanol (see Example 165). MS (ESI) m/z413/415 ([M+H]+); HRMS: calcd for C25H33CIN2O • 2.00 HCI, 484.1815; found (ESI), 413.2365. 169 WO 2005/037809 PCT/US2004/033990 Example 176: 1-[1-(3'-chloro-1 ,1'-biphenvl-4-yl)-2-(4-rnethvlpiperazin-1-vl)ethyl]cvclohexanol dihydrochloride [0475] In an analogous manner to Example 24, 1 -f 1 -(3'-chloro-1.1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1 -yl)ethyl icyclohexanol dihydrochloride was prepared from 1-[1-(3'-chloro-1,1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 167). MS (ESI) m/z 413/415 ({M+H]*); HRMS: calcd for C25H33CIN2O 2.00 HCI, 484.1815; found (ESI), 413.2347. Example 177: 1-[1-(3'-cvano-1.1'-biphenyl-4-yl)-2-(4-methvlpiperazin-1-yl)ethyl]cvclohexanol dihydrochloride [0476] In an analogous manner to Example 24, 1 -[1 -(3'-cyano-1,1 '-biphenyl-4-yl)-2-(4-mothylpiperazin-1 -yl)ethvlicyclohexanol 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 C2GH33N3O • 2.00 HCI, 475.2157; found (ESI), 404.2708. 170 WO 2005/037809 PCT/US2004/033990 . Example 178: 1-[2-(4-methy1piperazin-1-yl)-1-(3'-nitro-1.T-biphenvl-4-yl)ethylicvclohexanol dihvdrochloride [0477] In an analogous manner to Example 24, 1-[2-(4-methylpiperazin-1-vl)-1-(3'-nitro-1.1 '-biphenvl-4-vl)ethvl]cyclohexanol dihydrochlorido 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-methvlpiperazin-1 -yl)ethyl]cvclohexanol dihvdrochloride [0478] In an analogous manner to Example 24, 1-f1-(3'-methoxv-1,1'-biphenvl-4-yl)-2-(4-methvlpiperazin-1 -yl)ethyl]cyclohexanol dihydrochlorido 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. 171 WO 2005/037809 PCT/US2004/033990 ^ Example 180: H1-(4'-fluoro-1.1'-biphenvl-4-vl)-2-(4-methvlpiperazin-1-yl)ethvl]cvclohexanol dihydrochloride [0479] In an analogous manner to Example 1, step 2, 1 -[1 -(4-bromophenyl)-2-piperazin-1-ylethylicyclohexanol 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. [0480] In an analogous manner to Example 24, 1 -f 1 -(4-bromophenyl)-2-(4- methvlpiperazin-1-yl)ethyllcvclohexanol was prepared from 1-[1-(4-bromophenyl)-2-piperazin-1-ylethyl]cyclohexanol. MS (ESI) m/z 381/383 ([M+H]+); HRMS: calcd for C19H29BrN2O, 380.1463; found (ESI), 381.1525. [0481] In an analogous manner to Example 135, step 3, 1 -[1 -(4'-fluoro-1,1 '-biphenyl-4- yl)-2-(4-methvlpiperazin-1-vl)ethyl]cyclohexanol dihvdrochloride was prepared from 1-[1- (4-bromophenyl)-2-(4-methylpiperazin-1 -yl)ethyl]cyclohexanol using 4- fluorophenylboronic acid. Salt formation: A solution of 1-[1-(4'-fluoro-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 (1 mL) and stored in the refrigerator for 16 h. The resulting crystals were collected, washed with diethyl ether, and dried in vacuo to yield 1 -f 1 -(4'-fluoro-1.1 '-biphenyl-4-yl)-2-(4-methyipiperazin-1 -yl)ethylicyclohexanol dihvdrochloride. MS (ESI) m/z 397 ([M+H]+); HRMS: calcd for C25H33FN2O • 2.00 HCI, 468.2110; found (ESI), 397.2639 172 WO 2005/037809 PCT/US2004/033990 Example 181:1 -f1 -C4'-methvl-1.1 '-biphenyl-4-vl)-2-(4-methylpiperazin-1 -vl)ethvl1cvclohexanol dihydrochloride [0482] In an analogous manner to Example 135, step 3, 1 -[ 1 -(4'-methyl-1,1 '-biphenyl-4-yl)-2-(4-methylpiperazin-1-yl)ethyl1cvclohexanol dihydrochloride was prepared from 1 -[1-(4-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclohexanol (see Example 180, step 3) using 4-tolylboronic acid. Salt formation: A solution of 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 (1 mL) and stored in the refrigerator for 16 h. The resulting crystals were collected, washed with diothyl ether, and dried in vacuo to yield 1-f1-(4'-mo!hvl-1.1'-biphenyl-4-vl)-2-(4-methylpiperazin-1-yl)cthyl]cyclohexanol dihvdrochloride. MS (ESI) m/z 393 ([M+H]+); HRMS: calcd for C26H36N2O • 2.00 HCI, 464.2361; found (ESI), 393.2913. Example 182: 1-n-(3'-chloro-1,1'-biphenyl-4-yl]-2-piperazin-1-vlethvllcvclobutanol dihvdrochloride [0483] In an analogous manner to Example 1, step 1, tort-butyl 4-f(4-bromophenyl)(1-hydroxvcvclobutynacetvlipiperazine-i-carboxylate was prepared from (4-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-ww) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 453/455 ([M+H]*). 173 WO 2005/037809 PCT/US2004/033990 [0484] "' In an analogous manner to Example 135, step 2, tert-butvl 4-[2-(4-bromophenvl)-2-(1-hvdroxvcyclobutv0ethvllpiperazine-1-carboxvlate was prepared from te/t-butyl 4-[(4-bromophenyl)(1 -hydroxycyclobutyl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z 439/441 ([M+H]+). [0485] In an analogous manner to Example 135, step 3, /erf-butyl 4-r.2-(3'-chloro-1.1'-biphenvl-4-vl)-2-(1-hydroxvcvclobutvl)ethyl]piperazino-1-carboxvlate was prepared from /erf-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. [0486] In an analogous manner to Example 135, step 4, 1-[1-(3'-chloro-1,1'-biphenyl-4-yl)-2-piperazin-1 -ylethyncyclobutanol dihydrochloride was prepared from terf-butyl 4-[2-(3'-chloro-1,1'-biphenyl-4-yl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 371.3 ([M+HH; HRMS: calcd for C22H27CIN2O • 2.00 HCI, 442.1345; found (ESI), 371.1897. Example 183: 1-(2-piperazin-1-vl-1-[3'-(trifluoromethoxy)-1,1'-biphenvl-4-vHethyDcvclobutanol dihydrochloride [0487] In an analogous manner to Example 135, step 3, /erf-butyl 4-(2-(1- hvdroxvcvclobutyl]-2-f3'-(trifluoromethoxv)-1.1'-biphenvl-4-yl]ethyl|piperazine-1-carboxylate was prepared from terf-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1 -carboxylate (see Example 182, step 2) using 3- 174 WO 2005/037S09 PCT/US2004/033990 trifluorom^thoxyphenylboronic acid. MS (ES) m/z 521.4 ([M+H]+); HRMS: calcd for C28H35F3N2O4, 520.2549; found (ESI), 521.2639. [0488] In an analogous manner to Example 135, step 4, 1-(2-piperazin-1-yl-1-f3'-(trifluoromethoxyH, 1 '-biphenyl-4-vllethvl)cvclobutanol dihydrochloride was prepared from /erf-butyl 4-{2-(1-hydroxycyclobutyl)-2-[3'-(trifluoromethoxy)-1,1'-biphenyl-4-yl]ethyl}piperazine-1-carboxylate. MS (ES) m/z 421.3 ([M+H]+); HRMS: calcd for C23H27F3N2O2 ' 2.00 HCI, 492.1558; found (ESI), 421.2097. Example 184: 1 -F.1 -(3'.4'-dichloro-1.1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyllcyclobutanol dihydrochloride [0489] In an analogous manner to Example 135, step 3, /erf-butyl 4-[2-(3'.4'-dichloro-1.1'-biphenvl-4-vl)-2-(1-hvdroxvcvclobutvl)ethvHpiperazine-1-carboxylate was prepared from /erf-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 C27H3iCl2N?p3, 504.1946; found (ESI), 505.2036. [0490] In an analogous manner to Example 135, step 4, 1-M-(3',4'-dichloro-1,1'-biphenyl-4-yl)-2-piperazin-1-vlethyl]cyclobutanol dihydrochloride was prepared from tort-butyl 4-[2-(3',4'-dichloro-1,1 '-biphenyl-4-yl)-2-(1 -hydroxycyclobutyl)ethyl]piperazine-1 -carboxylate. MS (ES) m/z 405.3 ([M+H]+); HRMS: calcd for C22H26CI2N2O • 2.00 HCI, 476.0956; found (ESI), 405.1486. 175 WO 2005/037809 PCT/US2004/033990 Example ,185: 1-[1-(3'.5'-dichloro-1.1'-biphenvl-4-vl)-2-pipera^in-1-vlethyl]cyclobutanol dihydrochloride [0491] In an analogous manner to Example 135, step 3, tert-butyl 4-l2-(3'.5'-dichloro-1,1 '-biphenyl-4-yl)-2-(1 -hydroxycvclobutyl)ethyl]piperazine-1 -carboxylate was prepared from terf-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]4); HRMS: calcd for C27H34CI2N2O3, 504.1946; found (ESI), 505.2007; [0492] In an analogous manner to Example 135, step 4, 1-f1-(3',5'-dichloro-1.1'-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclobutanol dihydrochloride was prepared from tert-butyl 4-[2-(3',5'-dichloro-1,1l-biphenyl-4-yl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z 405.2 ([M+H]'); HRMS: calcd for C22H25CI2N2O 2.00 HCI, 476.0956; found (ESI), 405.151. Example 186: 1-(2-f(3f?)-3-fmethvlamino)piperidin-1-vl1-1-f3-(trifluoromethoxv)phenyl]ethyl)cvclohexanol dihydrochloride [0493] In an analogous manner to Example 1, step 1 /erf-butyl ((3fi)-1-((1-hvdroxvcvclohexvl)f3-(trifluoromethoxv)phenyl]acetyl)piperidin-3-vl)carbamate was 176 WO 2005/037809 PCT/US2004/033990 prepared from (1-hydroxycyclohexyl)[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 [0494] In an analogous manner to Example 13, step 2 1-(2-[(3/?)-3-(methvlamino)piperidin-1-yl]-i-[3-(trifluoromethoxv)phenyl]ethvl)cyclohexanol dihydrochloride was prepared from /erf-butyl ((3F?)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}piperidin-3-yl)carbamate. MS m/z 401; HRMS: calcd for C21H31F3N2O2 + H, 401.24159; found (ESI, [M+H]4), 401.2406. 177 Example 187: 1-(2-[(3/I?)-3-aminopiperidin-1-vll-1-r3-(trifluoromethoxy)phenyl]ethvl)cyclohexanol dihydrochloride WO 2005/037809 PCT/US2004/033990 [0495] In an analogous manner to Example 1, step 1 /erf-butyl f(3fi)-1-((1-hvdroxvcvclohexvl)[3-(trifluoromethoxv)phenvl1acetvl)pipGiiclin-3-vl)carbamate was prepared from (1-hydroxycyclohexyl)[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 [0496] In an analogous manner to Example 1, step 2 1-(2-|(3fl)-3-aminopiperidin-1-vH-1-[3-(trifluoromethoxv)phenvl1ethyl)cvclohexanol dihydrochloride was prepared from tert-butyl ((3/:?)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}piperidin-3-yl)carbamate. HRMS: calcd for C20H29F3N2O2 + H, 387.22594; found (ESI, [M+Hp), 387.2248. Example 188: 1-(2-f(3fl)-3-(dimethylamino)piperidin-1-yl'l-H3-(trifluoromethoxv)phenyllethyl)cyclohexanol dihydrochloride [0497] In an analogous manner to Example 36, 1-(2-f(3ff)-3-(dimethylamino)piperidin-1-yl1-H3-(trifluoromethoxv)phenyllethvl)cyciOhexanol dihydrochloride was prepared from 1 -{2-[(3F?)-3-aminopiperidin-1 -y|]-i -[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol (See Example 187). MS (ESI) m/z 415; HRMS: calcd for C22H33F3N2O2 + H, 415.25724; found (ESI, [M+H]*), 415.2596. Example 189: 1-(2-r(3S)-3-(methylamino)piperidin-1-yl]-1-f3-(trifluoromethoxy)phenvllethyl)cvclohexanol dihydrochloride 178 WO 2005/037809 PCT/US2004/033990 [0498] In an analogous manner to Example 1, step 1, tert-butyl ((3S)-1-((1-hvdroxvcvclohexvl)[3-(trifluoromethoxv)phenvllacetvl)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/z501.1 [0499] In an analogous manner to Example 13, step 2, 1-(2-f(3S)-3-(methvlamino)piperidin-1-vl1-1-f3-(trifluoromethoxv)phenvl]ethyl)cvclohexanol dihydrochloride was prepared from /e/t-butyl ((3S)-1-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}piperidin-3-yl)carbamate. MS /77/z401; HRMS: calcd for C2iH31F3N2O2 + H, 401.24159; found (ESI, [M+H]+), 401.2419. Example 190: 1-(2-[(3S)-3-aminopiporidin-1-vl1-1-[3-(trifluoromethoxy)phenyl]ethvl)cyclohexanol dihydrochloride [0500] In an analogous manner to Example 1, step 1, fert-buty) ((3S)-1-((1-hvdroxvcvclohexyl]f3-(trifluoromethoxy)phGnvl1acetvl}piperidin-3-vl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference 179 WO 2005/037809 PCT/US2004/033990 Example 1-f) and (S)-(+)-3-t-butoxycarbonylaminopiperidine (Moon, S.; Lee, S., Synth. Commun. 1998, 28(21), 3919-3926.) MS (ES) m/z501.1 [0501] In an analogous manner to Example 1, step 2, 1 -(2-[(3S)-3-aminopiperidin-1 -Vl1-1-f3-(trifluoromethoxv)phenvllethvl)cyclohoxanol dihydrochloride was prepared from rerf-butyl ((3/^-1 -{(1 -hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}piperidin-3-yl)carbamate. HRMS: calcd for C2oH29F3N202 + H, 387.22594; found (ESI, [M+H]4), 387.2248. Example 191: 1-(2-f(3S)-3-(dimethvlamino)piperidin-1-vl1-1-f3-(trifluoromethoxv)phenyliethvllcvclohexanol dihydrochloride [0502] In an analogous manner to Example 36, 1-(2-f(3S)-3-(dimethylamino)piperidin-1 -yli-1 -[3-(trifluoromethoxy)phenyllethyl)cyclohexanol dihydrochlorido was prepared from 1 -{2-[(3S)-3-aminopiperidin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol (See Example 190). MS (ESI) m/z415; HRMS: calcd for C22H33F3N2O2 + H, 415.25724; found (ESI, [M+H]4), 415.2549. Example 192: 1-(1-f4-(benzvloxy)-3-chlorophonyl]-2-[(3/?)-3-(methylamino)piperidin-1- yliethyDcyclohexanol dihydrochloride ISO WO 2005/037809 PCT/US2004/033990 [0503] In an analogous manner to Example 1, step 1, /erf-butyl ((3f?)-1-ff4-(benzvloxv)-3-chlorophenvll(1-hvdroxvcvclohexyl)acetyl]piperidin-3-vl)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 [0504] In an analogous manner to Example 13, step 2, 1-(1-[4-(benzyloxy)-3-chlorophenyll-2-[(3/?)-3-(methvlamino)piDeridin-1-yl]ethvl)cvclohexanol dihydrochloride was prepared from ferf-butyl {(3ft)-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. 181 Example 193: 1 -(2-f (3/7)-3-aminopiperidin-1 -yli-1 -[4-(benzvloxvV3-chlorophenynethyllcvclohexanol dihydrochloride WO 2005/037809 PCT/US2004/033990 [0505] In an analogous manner to Example 1, step 1, /erf-butyl ((3/?)-1-[f4-(benzv)oxv)-3-chlorophenyll( 1 -hvdroxvcvclohexvl)acetvHpiperidin-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/z557.1 [0506] In an analogous manner to Example 1, step 2, 1-(2-r(3f?)-3-aminopiperidin-1-vll-1-[4-(benzvloxv)-3-chlorophenvl]ethvl)cvclohexanol dihydrochloride was prepared from terf-butyl {(3f?)-1-[[4-(benzyloxy)-3-chlorophenyl](1- hydroxycyclohexyl)acetyt]piperidin-3-yl}carbamatG. MS m/z 443; HRMS: calcd for C26H3r,CIN2O2 + H, 443.24653; found (ESI, [M+H]+). 443.2487. Example 194: 1 -(1 -[4-(benzyloxv)-3-chlorophenyl]-2-f (3fl)-3-(dimethylamino)piperidin-1 - Vllethyljcyclohexanol dihydrochloride [0507] In an analogous manner to Example 36, 1 -(1 -f4-(benzvloxv)-3-chlorophenyll-2-[(3fl)-3-(dimethylamino)piperidin-1-ynethyl)cyclohexanol dihydrochloride was prepared from 1-{2-[(3R)-3-aminopiperidin-1-yl]-1-[4-(benzyloxy)-3- chlorophenyl]ethyl}cyclohexanol_(Soe Example 193). MS (ESI) m/z 415; HRMS: calcd for C28H39CIN2O2 + H, 471.27783; found (ESI, [M+H]+), 471.2767. Example 195: 1-(1-r4-(benzvloxy)-3-chlorophenvll-2-r(3S)-3-(methvlamino)piperidin-1- yliethvllcyclohexanol dihydrochloride 182 WO 2005/037809 PCT/US2004/033990 [0508] In an analogous manner to Example 1, step 1, teft-butvl {(3SH-H4-(benzvloxv)-3-chlorophenyl](1-hvdroxvcyclohexvl)acetvllpiperidin-3-vllcarbannate 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/z557.1 [0509] In an analogous manner to Example 13, step 2, 1 -(1 -f4-(bonzyloxv)-3-chloroDhenyl]-2-[(3S)-3-(methvlamino)pipGridin-1-yl]ethyl)cvclohexanol dihydrochloride was prepared from /erf-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 183 Example 196: 1-(2-r(3S)-3-aminopiperidin-1-yl]-1-r.4-(bonzyloxv)-3-chloroQhcnyl]ethyl)cyciohexanol dihydrochloride WO 2005/037809 PCT/US2004/033990 [0510] In an analogous manner to Example 1, step 1, /erf-butyl f(3S)-1-ff4-(benzvloxv)-3-chlorophenyl](1-hvdroxvcyclohexvl)acetvl1piperidin-3-vl)caibamate 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/z557.1 [0511] In an analogous manner to Example 1, step 2, 1 -(2-f(3S)-3-aminopiperidin-1 -vl]-1-[4-(benzvloxv)-3-chlorophenvl]ethyl)cvclohexanol dihydrochloride was prepared from tert-butyl {(3S)-1-[[4-(benzyloxy)-3-chlorophenyl](1- hydroxycyclohexyl)acetyl]piperidin-3-yl}carbamate. MS m/z443; HRMS: calcd for C26H35CIN2O2 + H, 443.24653; found (ESI, [M+H]+), 443.2482. Example 197: 1-(1-[4-(benzvloxv)-3-chlorophenyll-2-[(3S)-3-(dimethylamino)piperidin-1- yllethyl)cyclohexanol dihydrochloride [0512] In an analogous manner to Example 36, 1 -(1 -f4-(benzyloxv)-3-chlorophenvH-2-f(3S)-3-(dimethylamino)piperidin-1-ynethyl}cyclohexanol dihydrochloride was prepared from 1 -{2-[(3S)-3-aminopiperidin-1 -yl]-1 -[4-(benzyloxy)-3- chlorophenyl]ethyl}cyclohexanol_(Seo Example 196). HRMS: calcd for C28H39CIN2O2 + H, 471.27783; found (ESI, [M+H]+), 471.2766. Example 198: 1-1-11 -(3-chlorophenyl)-2-[(3S)-3-(methvlamino)pvrrolidin-1 -yliethyPcyclohexanol dihydrochloride 184 WO 2005/037809 PCT/US2004/033990 [0513] In an analogous manner to Example 1, step 1, tert-butyl ((3S)-1-[(3-chlorophenvl)(1-hvdroxycvclohexvl)acetyl]Dvrrolidin-3-vl}carbamate was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)aceticacid (Reference Example 1a) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 437.0 [0514] In an analogous manner to Example 13, step 2, 1 -(1 -(3-chlorophenyl)-2-[(35)-3-(methvlamino)pvrrolidin-1-yl]ethvl)cyclohexanol dihydrochloridc was prepared from /erf-butyl {(3S)-1 -[(3-chlorophenyl)(1 -hydroxycyclohexyl)acetyl]pyrrolidin-3-yl}carbamate MS (ES) m/z337.2; HRMS: calcd for C19H:>9CIN2O + H, 337.20467; found (ESI, [M+H]f), 337.2034. Example 199: 1-(1-(3-chlorophenvl)-2-f(3S)-3-(dimethylamino)pvrrolidin-1-vliethyDcyclohexanol dihydrochloride [0515] In an analogous manner to Example 36, 1 -{1 -(3-chlorophenyl)-2-f(3S)-3-(dimethvlamino)pvrrolidin-1-yl]ethvl}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 -(1 -(3-chlorophenyl)-2-[(3R)-3-(methvlamino)pyrrolidin-1 -yllethyl)cyclohexanol dihydrochloride 185 WO 2005/037809 ' PCT/US2004/033990 [0516] In an analogous manner to Example 1, step 1, fe/f-butyl {(3f?)-H(3-chlorophenviy(1-hvdroxvcvclohexyl]acetyl]pvrrolidin-3-vl)carbamate was prepared from (3rchlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1a) and (3R)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS m/z 437 [0517] In an analogous manner to Example 13, step 2, 1 -(1 -(3-chlorophenyl)-2-f(3R)-3-(methvlamino)pyrrolidin-1-yl"]ethvl}cvclohexanol 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 Ci9H29CIN2O + H, 337.20467; found (ESI, [M+H]+), 337.2043. Example 201: 1-[2-[(3fl)-3-aminopvrrolidin-1-yl]-1-(3-chlorophenyl)ethvllcyclohexanol dihydrochloride [0518] In an analogous manner to Example 1, step 1, fe/f-butyl ((3F?)-1-[(3-chlorophenvl)(1-hvdroxvcvclohexyl]acetyl]pyrrolidin-3-vl)carbamate was prepared from (3-chlorophenyi)(1-hydroxycyclohexyl)acetic acid (Reference Example 1a) and (3R)-(~)-3-(tert-butoxycarbonylamino)pyrrolidine. MS m/z437 [0519] In an analogous manner to; Example 1, step 2, 1 -[2-f(3f?)-3-aminopyrrolidin-1 -vli-1 -(3-chlorophenvl)ethvllcyclohexanol dihvdrochloride was prepared from te/t-butyl 186 WO 2005/037809 PCT/US2004/033990 {(3R)-1--[(3-chlorophenyl)(1 -hydroxycyclohoxyl)acetyl]pyrrolidin-3-yl}carbamate MS (ESI) m/z 323; HRMS: calcd for C-8H27CIN2O + H, 323.18901; found (ESI, [M+H]+), 323.1895. Example 202: 1 -(1 -(3-chlorophenvl)-2-r(3ffl-3-(dimethvlamino)pyrrolidin-1 -yllethyl)cvclohexanol dihydrochloride [0520] In an analogous manner to Example 36, 1 -(1 -(3-chlorophenyl)-2-f(3fl)-3-(dimethvlamino)pvrrolidin-1-vl1ethvl)cyclohoxanol dihydrochloride was prepared from 1 -[2-[(3fl)-3-aminopyrrolidin-1-yl]-1-(3-chlorophenyl)ethyl]cyclohexanol (See Example 201). MS (ESI) m/z 351; HRMS: calcd for C20H31CIN2O + H, 351.22031; found (ESI, [M+H]+), 351.2193. Example 203: 1-r2-r(3S)-3-(methylamino)pvrrolidin-1-yll-1-(2-naphthyDethyl]cyclohexanol dihydrochloride [0521] In an analogous manner to Example 1, step 1, ferf-butyl ((3S)-1-f(1-hvdroxvcvclohexvl)(2-naphthynacetvllpyrrolidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1q) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrro!idine. MS m/z 437 [0522] In an analogous manner to Example 13, step 2, 1-[2-[(3S)-3-(methvlamino)pvrrolidin-1-vl]-1-(2-naphthvl)ethvl]cvclohexanol dihydrochloride was prepared from fert-butyl {(3S)-1-[(1-hydroxycyclohexyl)(2-naphthyl)acetyl]pyrrolidin-3- 187 WO 2005/037809 PCT/US2004/033990 yljcarbamate MS (ESI) m/z 353; HRMS: calcd for C23H32N2O + H, 353.25929; found (ESI, [M+H]*), 353.2582. Example 204: 1 -[2-f(3S)-3-aminopvrrolidin-1 -vll-1 -(2-naphthyl)ethvllcyclohexanol dihydrochloride [0523] In an analogous manner to Example 1, step 1, tert-butyl ((3S)-1-f(1-hvdroxvcvclohexv0(2-naphthv0acetvl1pyrrolidin-3-vllcarbamate was prepared from (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1q) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS m/z 437 [0524] In an analogous manner to Example 1, step 2, 1 -[2-[(3S)-3-aminopvrrolidin-1 -yli-1 -(2-naphthyl)ethyncyclohexanol dihydrochloride was prepared from tert-butyl {(3S)-1-[(1-hydroxycyclohexyl)(2-naphthyl)acetyl]pyrrolidin-3-yl}carbamate MS (ESI) m/z 339; HRMS: calcd forC^HaoNaO + H, 339.24364; found (ESI, [M+H]+), 339.2441. 1XS Example 205: 1-[2-r(3S)-3-(dimcthylamino)pyrrolidin-1-vl1-1-(2-naphthyDethylicyclohexanol dihydrochloride WO 2005/037809 PCT/US2004/033990 [0525] In an analogous manner to Example 36, 1-[2-f(3S)-3-(dimethvlamino)pvrroliciin-JbYll-1 -(2-naDhthyl]ethvllcvclohexanol dihvdrochloride 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 C2