WO 2005/037207 PCT/US2004/033730 ALKANOL AND CYCLOALKANOL-AMINE 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. 60/510,942 filed October 14, 2003, 60/561,422 filed April 12, 2004, and 60/569,884 filed May 11, 2004, the entire disclosures of which are herein incorporated by reference. FIELD OF THE INVENTION [0002] The present invention relates to alkanoyl and cycloalkanoyl-amine 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 l WO 2005/037207 PCT/US2004/033730 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 the epreads 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 2005/037207 PCT/US2004/033730 Physiology of Menopausa! 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 menopausai stage of life is associated with a wfde 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 hypothaiamus. 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 2005/037207 PCT/US2004/<13373<) 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-biockers, with varying degree of success (Waldinger etai, Maturitas, 2000, 36(3): 165-168). [0010] It has been reported that ct2-adrenergic receptors play a role in thermoregulatory dysfunctions (Freedman etal, 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 adrenergica2 receptors, i.e., are a2A, a2B, a2C and a2D (Mackinnon et al, TIPS, 1994, 15: 119; French, Pharmacol. Ther., 1995, 68: 175). It has been reported that a non-select a2-adrenoceptor antagonist, yohimbine, induces a flush and an a2-adrenergic receptor agonist, clonidine, alleviates the yohimbine effect (Katovich, et al., Proceedings of the Society for Experimental Biology & Medicine, 1990, 193(2): 129-35, Freedman et al, Fertility & Sterility, 2000, 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 necessary to abate hot flash described herein and known in the related arts. [0011] Given the complex multifaceted nature of thermoregulation and the interplay between the CNS and PNS in maintain ing thermoregulatory homeostasis, muliiple 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 alkanoyl and cycloalkanoyl-amine 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 2005/037207 PCT/US2004/033730 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 pharmaceutically salt thereof; wherein: W is H or OR9; R1 and R2 are, independently, H, OH, alkyl, alkoxy, halo, trifluoromethyl, alkanoyloxy, or together form, methylene or methylenedioxy; R5 is H or (C1-C6)alkyl; R6 and R7 are, independently, (C1-C6)alkyl or (C3-C6)cycloalkyl; or R6 and R7, together with the carbon atom to which they are attached, form a ring of 4 to 8 carbon atoms; where any ring carbon atom is optionally replaced with N, S, or O; where said ring is optionally substituted with one to four substituents independently selected from the group consisting of (C1-C6)alkyl, branched (C1-C6)alkyl, OH, halo, and trifluoromethyl; and where said ring is optionally fused to a carbocyclic ring or aromatic ring of 5-8 carbon atoms (where one to two carbon atoms of said fused ring can 5 WO 2005/037207 PCT/US2004/033730 be optionally replaced with N, 0, or S and where said fused ring is optionally substituted with one to four substituents independently selected from the group consisting of (C1-C6)alkyl, branched (C1-C6)alkyl, OH, halo, and trifluoromethyl); R8 is H or (C1-C6)alkyl; or R5 and R8, together with the nitrogen atom to which R8 is attached, form a heterocyclic ring; where said heterocyclic ring is optionally substituted with one to four substituents independently selected from the group consisting of (C1-C6)alkyl, branched (C1-C6)alkyl, OH, halo, and trifluoromethyl; R9 is H, (CrC4)alkyl, or (C1-C4)alkyl-C(=O); t is 1, 2, or 3; and x is O, 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. 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 WO 2005/037207 PCT/US2004/03373O 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 pharmaceuticaliy 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 pharmaceuticaliy 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 pharmaceuticaiiy 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 pharmaceuticaliy acceptable salt thereof. [0020] In another embodiment, the present invention is directed to methods for treating or preventing gastrointestinal or genitourinary disorder, particularly stress incontinence or urge urinary incontinence, in a subject in need thereof, comprising the step of: administering to said subject an effective amount of a compound of formula I or pharmaceuticaliy 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 7 WO 2005/037207 PCT/US2004/033730 or pharmaceutically acceptable salt thereof. [0022] In another embodiment, the present invention is directed to methods for treating or preventing fibromyiagia 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, a1 and a2-adrenergic). DETAILED DESCRIPTION OF THE INVENTION [0026] The present invention is directed to alkanoyl and cycioalkanoyl-amine 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, fibromyiagia 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 8 WO 2005/037207 PCT/US2004/033730 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. "D°C" and D "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",1 is abbreviated NR1. "Selective norepinephrine reuptake inhibitor" is abbreviated SNRI. "Serotonin reuptake inhibitor" is abbreviated SRI. "Selective serotonin reuptake inhibitor" is abbreviated SSRI. "Norepinephrine" is abbreviated NE. "Serotonin is abbreviated 5-HT. "Subcutaneous" is abbreviated sc. "Intraperitoneal" is abbreviated ip. "Oral" is abbreviated po. [0031] In the context of this disclosure, a number of terms shall be utilized. The term "treatment" as used herein includes preventative (e.g., prophylactic), curative or palliative treatment and "treating" as used herein also includes preventative, curative 9 WO 2005/037207 PCT/US2OO4/033730 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, cr 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 the condition to be alleviated, hormone levels, age, sex, weight of the individual, the state of being of the patient, and the severity of the pathological condition being treated, concurrent medication or special diets then being followed by the particular patient, and other factors which those skilled in the art will recognize, with the appropriate dosage ultimately being at the discretion of the attendant physician. Dosage regimens may be adjusted to provide the improved therapeutic response. An effective amount is also one in which any toxic or detrimental effects of the components are outweighed by the therapeutically beneficial effects. [0034] Preferably, the compounds of the present invention are administered at a dosage and for a 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 10 WO 2005/037207 PCT/US2004/033730 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, sexuaf 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. [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, 11 WO 2005/037207 PCT/US2004/033730 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. [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 12 WO 2005/037207 PCT/US2004/033730 "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-rnenopausal, or post-menopausai 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-menopausa!" means after the menopause. "Ovariectomy" means removal of an ovary or ovaries and can be effected according to Merchenthaler era/., Maturitas, 1998, 30(3): 307-316. [0046] "Side effect" refers to a consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other thert the one sought to be benefited by its administration. In the case, for example, of high doses of NRIs or NRI/SRl 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 P,t 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 13 WO 2005/037207 PCT/US2004/03373I) 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 isohexy!. 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] "Alkoxycarbonyi," 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. [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 muiticyclic aromatic ring system having from about 5 to about 50 carbon atoms (and all combinations and subcombinations of ranges and specific numbers of 14 WO 2005/037207 PCT/US2OO4/03373O carbon atoms therein), with from about 6 to about 10 carbons being preferred. Ntin-limiting examples include, for example, phenyl, naphthyl, anthracenyl, and phenaffthrenyl. [0057] "Heteroaryl," as used herein, refers to an optionally substituted, mono-; di-, tri-, or other multicyclic aromatic ring system that includes at least one, and preferably from 1 to about 4 sulfur, oxygen, or nitrogen heteroatom ring members. Heteroaryl groups can have, for example, from about 3 to about 50 carbon atoms (and all combinations and subcombinations of ranges and specific numbers of carbon atoms therein), with from about 4 to about 10 carbons being preferred. Non-limiting examples of heteroaryl groups include, for example, pyrryl, fury!, pyridyi, 1,2,4-thiadiazolyl, pyrimidyl, thienyl, isothiazolyl, imidazolyl, tetrazolyl, pyrazinyl, pyrimidyl, quinolyl, isoquinolyl, thiophenyl, benzothienyl, isobenzofuryl, pyrazolyl, indolyl, purinyl, carbazolyl, benzimidazolyi, 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 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-indazo!e, 2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl, 4-piperidonyl, 4aH-carbazole, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl, acridinyl, azocinyl, benzimidazolyi, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, 15 WO 2005/037207 PCT/US20M4/0337J0 benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, carbazoly!, 4H-carbazolyl, a, ?-, or Y-carbo|inyl. chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H.6H-1,5,2-dithiazinyI, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1 H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindoiinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl., oxazolyl, oxazolidinylpyrimidinyl, pHenanthridinyl, phenanthrolinyl, phenoxazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl, purinyl, pyranyi, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl, quinoiinyl, 4H-quinolizinyl, quinoxalinyl, quinuciidinyl, carbolinyl, tetrahydrofuranyl, telrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyI, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazoly!, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazoIyl, 1,2,4-triazolyl, 1,2,5-triazolyI, 1,3,4-triazoly!, xanthenyl. Preferred heterocycles include, but are not limited to, pyridinyl, furanyi, thienyl, pyrrolyl, pyrazolyl, imidazolyl, indolyl, benzimidazolyl, 1 H-indazolyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, or isatinoyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles. [0059] "Heteroarylmethyl," as used herein, refers to the group R-CH2- where R is a heteroaryl group, as defined herein. [0060] "Heteroarylmethyloxy," as used herein, refers to the group R-CH2-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. 16 WO 2005/037207 PCT/US2004/033730 [0062] "Heteroarylmethyloxy," as used herein, refers to the group R-CH2-O- where R is a heteroary! 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]heptany[], 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. [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-. WO 2005/037207 PCT/US2004/033730 [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 pharmaceutically salt thereof; wherein: W is H or OR9; R1 and R2 are, independently, H, OH, alkyl, alkoxy, halo, trifluoromethyl, alkanoyloxy, or together form, methylene or methylenedioxy; R5 is H or (C1-C6)alkyl; R6 and R7 are, independently, (C1-C6)alkyl or (C3-C6)cycloalkyl; or R6 and R7, together with the carbon atom to which they are attached, form a ring of 4 to 8 carbon atoms; where any ring carbon atom is optionally replaced with N, S, or O; where said ring is optionally substituted with one to four substituents independently selected from the group consisting of (C1-C6)alkyl, branched (C1-C6)alkyl, OH, halo, and trifluoromethyl; and where said ring is optionally fused to a carbocyclic ring or aromatic ring of 5-8 carbon atoms (where one to two carbon atoms of said fused ring can be optionally replaced with N, O, or S and where said fused ring is optionally substituted with one to four substituents independently selected from the 18 WO 2005/037207 PCT/US2004/033730 group consisting of (C1-C6)alkyl, branched (C1-C6)a!kyl, OH, halo, and trifluoromethyl); !B8 is H or (C1-C6)alkyl; or R5 and R8, together with the nitrogen atom to which R8 is attached, form a heterocyclic ring; where said heterocyclic ring is optionally substituted with one to four substituents independently selected from the group consisting of (Ci-C6)alkyl, branched (C1-C6)alkyl, OH, halo, and trifluoromethyl; R9 is H, (CrC4)alky!, or (C1-C4)alkyI-C(=O); t is 1, 2, or 3; and x is 0, 1, or 2. [0072] In certain preferred embodiments, W is OR9; R1 and R2 are, independently, H, OH, alkyl, alkoxy, halo, trifluoromethyl, alkanoyloxy, or together form, methylenedioxy; R5 is H or (C1-C6)alkyl; RB and R7 are, independently, (C1-C6)alkyl or (C3-C6)cycloalkyl; or R6 and R7, together with the carbon atom to which they are attached, form a ring of 4 to 8 carbon atoms; where any ring carbon atom is optionally replaced with N, S, or O; where said ring is optionally substituted with one to four substituents independently selected from the group consisting of (C1-C6)alkyl, branched (C1 C6)alkyl, OH, halo, and trifluoromethyl; and where said ring is optionally fused to a carbocyclic ring or aromatic ring of 5-8 carbon atoms (where one to two carbon atoms of said fused ring can be optionally replaced with N, O, or S and where said fused ring is optionally substituted with one to four substituents independently selected from the group consisting of (C1-C6)alkyl, branched (C1-C6)alkyI, OH, halo, and trifluoromethyl); R8 is H or (C1-C6)alkyl; or R5 and R8, together with the nitrogen atom to which R8 is attached, form a heterocyclic ring; 19 WO 2005/037207 PCT/US2004/033730 where said heterocyclic ring is optionally substituted with one to four substituents independently selected from the group consisting of (C1-C6)alkyi, branched (C1-C6)alkyl, OH, halo, and trifiuoromethyl; R9 is H; t is 1; and xis 1. [0073] In certain preferred embodiments, W is H. In certain other preferred embodiments, W is OR9. [0074] In certain preferred embodiments, R1 and R2 are, independently, H, OH, alkyl (especially methyl, ethyl, propyl, and butyl), alkoxy (especially methoxy and ethoxy), or halo (especially chloro, fluoro, and bromo). [0075] In certain preferred embodiments, R5 is H or (C1-C6)alkyl (especially methyl, ethyl, propyl, and butyl). [0076] In certain preferred embodiments, R6 and R7 are, independently, (C1-C6)alkyl (especially methyl, ethyl, propyl, and butyl) or (C3-C6)cycloalkyl (especially cyciopropyl, cyclobutyl, and cyclohexyi). [0077] In certain preferred embodiments, R° and R7, together with the carbon atom to which they are attached, form a ring of 4 to 8 carbon atoms [0078] In certain preferred embodiments, R8 is H or (C1-C6)alkyl (especially methyl, ethyl', propyl, or butyl). [0079] In certain preferred embodiments, R5 and R8, together with the nitrogen atom to which R8 is attached, form a heterocyclic ring. [0080] In certain preferred embodiments, R9 is H or (C1-C4)alkyl (especially methyl, ethyl, and propyl). 20 WO 2005/037207 PCT/US2004/U3373O [0081] In certain preferred embodiments, t is 1. In certain other preferred embodiments, t is 2. In yet certain other preferred embodiments, t is 3. [0082] 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 including the carbon to which they are attached are 4, 5, 6 or 7 membered rings in which one ring atom is optionally oxygen or nitrogen, said ring being optionally substituted by one to four substituents selected from alkyl of 1 to 6 carbon atoms and hydroxy; and wherein said ring is also optionally fused to a carbocyclic ring of 6 carbon atoms. For example Rs and R7 together with the carbon may form a cyclohexyl ring optionally substituted by an alkyl of 1 to 6 carbon atoms or OH. Other examples of R6 and R7 are alkyl of 1 to 6 carbon atoms or cyclopropyl. R1 and R2 are each for example hydrogen, halo and alkoxy of 1 to 6 carbon atoms. R8 may for example represent H or alkyl of 1 to 6 carbon atoms. Examples of W are H or OH. R5 is for example K An example of x is 1. An example of t is 1. [0083] Preferred compounds of formula I include: 4-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]tetrahydro-2H-pyran-4-ol dihydrochloride; 4-[1-(3-chlorophenyl)-2-(4-methylpiperazin-1-yl)ethyl]tetrahydro-2H-pyran-4-ol dihydrochloride; 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]-4-tert-butylcyclohexanol dihydrochloride; 4-[1 -(3-bromophenyl)-2-piperazin-1 -y!ethyl]heptan-4-ol dihydrochloride; 4-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]heptan-4-ol dihydrochloride; 21 WO 2005/037207 PCT/US2004/033730 1 -[1 -(3-bromo-4-methoxyphenyl)-2-piperazin-1 -ylethyl]-4-tert-butylcyclohexanol dihydrochloride; 2-(3-chlorophenyl)-1,1-dicyclopropyl-3-(4-methy!pipera2in-1-yl)propan-1-ol dihydrochloride; 1-[1-(3-bromophenyl)-2-pipera2in-1-y!ethyI]-3,3,5,5-tetramethyIcyc!ohexanol dihydrochloride; 1-[1-(3-bromophenyI)-2-(4-methyIpiperazin-1-yl)ethyl]-3,3,5,5-tetramethylcyclohexanol dihydrochloride; 4-tert-butyl-1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride; 2-(3-chlorophenyl)-3-ethyl-1-(4-methylpiperazin-1-yl)pentan-3-ol dihydrochloride; 1 -[1 -(3-bromophenyl)-2-piperazin-1 -ylethyi]-4-tert-butylcyclohexanol dihydrochloride; 4-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]tetrahydro-2H-pyran-4-ol dihydrochloride; 2-[1-(3-bromophenyl)-2-piperazin-1-yIethyl]adamantan-2-ol dihydrochloride; 4-[1 -{3-bromo-4-methoxyphenyl)-2-piperazin-1 -ylethy!]tetrahydro-2H-pyran-4-ol dihydrochloride; 4-[1-(3,4-dichlorophenyl)-2-piperazin-1-y!ethyl]-1-methylpiperidin-4-ol trihydrochloride; 2-(3-bromophenyl)-3-ethyl-1 -piperazin-1 -ylpentan-3-ol dihydrochloride; 4-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]heptan-4-ol dihydrochloride; 2-(3-chlorophenyl)-3-ethyl-1-piperazin-1-y!pentan-3-ol dihydrochloride; 4-[1 -(3-bromophenyl)-2-piperazin-1 -ylethyl]-1 -methylpiperidin-4-ol dihydrochloride; 2-(3-bromo-4-methoxyphenyl)-3-ethyl-1-piperazin-1-ylpentan-3-ol dihydrochloride; 2-(3-bromo-4-methoxyphenyl)-3-ethyl-1-(4-methyipiperazin-1-yl)pentan-3-ol dihydrochloride; 1 -[1 -(3-chlorophenyl)-2-piperazin-1 -ylethyl]decahydronaphthalen-1 -ol dihydrochloride; 22 WO 2005/037207 PCT7US2004/033730 1-[1-(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazin-1-yl)ethy!]-4-tert-butylcyclohexanoldihydrochloride; 2-[1-(3-chlorophenyl)-2-piperazin-1-ylethyI]decahydronaphthalen-2-ol dihydrochloride; 4-tert-butyl-1-[1-(3-chlorophenyl)-2-(4-methylpipera2in-1-yl)ethyl]cyclohexanoI dihydrochloride; 1-[2-(3-ch!oropheny!)-2-cyclopentylethyl]piperazine dihydrochloride; 1-[2-(3-chlorophenyl)-2-cyclopentylethyI]-4-methylpiperazine dihydrochloride; 1-[2-(3-chlorophenyl)-2-cyclohexylethyl]piperazine dihydrochloride; 1-[2-(3-chlorophenyl)-2-cyc!ohexylethyl]-4-methylpiperazine dihydrochloride; 1-[2-(3-chlorophenyl)-2-cycloheptyl9thyl]piperazine dihydrochlonde; 1-[2-(3-chlorophenyl)-2-cycloheptylethyl]-4-methylpiperazine dihydrochloride; 2-[1 -(3-chlorophenyl)-2-piperazin-1 -ylethyljcyclohexanol dihydrochloride; 3-(3-chlorophenyl)-2-methyl-4-piperazin-1-ylbutan-2-ol dihydrochloride; 3-(3-chlorophenyl)-2-methyl-4-(4-methylpiperazin-1-yl)butan-2-ol dihydrochloride; 3-(3-chlorophenyl)-2-methyI-4-(4-methylpiperazin-1-yl)butan-2-ol dihydrochloride; 1-[1-(3-chlorophenyl)-2-(4-methylpiperazin-1-yl)ethyl]-3,3,5,5-tetramethyl cyclohexanol dihydrochloride; 2-[1 -(1 -naphthyl)-2-piperazin-1 -ylethyl]decahydronaphthalen-2-ol dihydrochloride; 1 -[1 -(3-chlorophenyl)-2-(4-methylpiperazin-1 -yl)ethyl]decahydro naphthalen-1 -ol dihydrochloride; 2-[1 -(3-chlorophenyl)-2-(4-methylpiperazin-1 -yl)ethyl]decahydro naphthalen-2-ol dihydrochloride; 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]-4-methylcyclohexanol dihydrochloride; 1 -[1 -(3-chlorophenyl)-2-(4-methylpiperazin-1 -y()ethyl]-4-methylcyclohexanol dihydrochloride; 1 -[1 -{3-chlorophenyl)-2-(4-methylpiperazin-1 -y()ethyl]-4-ethy!cyc!ohexanol dihydrochloride; and pharmaceutically acceptable salts thereof. 23 WO 2005/037207 PCT/US2004/033730 [0084] 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 weil as the substantially pure stereoisomers are within the scope of the invention. The term "substantially pure," as used herein, refers to at least about 90 mole %, more preferably at least about 95 mole %, and most preferably at least about 98 mole % of the desired stereoisomer is present relative to other possible stereoisomers. Preferred enantiomers may be isolated from racemic mixtures by any method known to those skilled in the art, 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); Eiiel, 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). [0085] The present invention includes prodrugs of the compounds of formula !. "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). [0086] 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 24 WO 2005/037207 PCT7US2004/033730 unsolvated forms for the purpose of the present invention. [0087] 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, muitikilogram or commercial industrial scale. [0088] 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 hydroxyi 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. 25 [0089] This invention also provides processes for preparing the compounds of formula I which processes include one of the following: a) reducing a compound of formula WO 2005/037207 PCT/US2004/033730 wherein R1, R2, R5"8, x, t and W are as defined above, 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! herein RB is hydrogen with an aikylating 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. 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 1-2). 26 WO 2005/037207 PCT/US2004/033730 where Y = H, R8, or P; P is an amine protecting group, preferably but not limited to tert-butoxycarbonyl; and R1, R2, R3, R4, Rs, Re, R7, Rs, and x are as previously defined. [0090] 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 = ferf-butoxycarbonyl, any conventional method for the deprotection of a carbarnate 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. [0091] 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 27 WO 2005/037207 PCT/US2O04/033730 acid to form an amide. In the preferred embodiment of this invention, the carboxyiic acid is treated with benzotriazol-1-yloxytris(dimtheylamino)phosphonium hexafluoro phosphate in the presence of an appropriately substituted secondary or primary amine and triethylamine. [0092] 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 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 carboxyiic acid. This reaction is carried out by any conventional means of reacting the alpha carbon atom of a carboxyiic 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 -509C being preferred. [0093] 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, a mixture of the amine and an appropriately substituted aldehyde or ketone in metnylene chloride is treated' with trisacetoxyborohydride. 28 WO 2005/037207 PCT/US2004/033730 [0094] 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 jsomers of either the amide of formula V! or formula VII, where Y = P, or tne amine of formula ! or formula VIII via either High Performance Liquid Chromatography (HPLC) or via Supercritical Fluid Chromatography. [0095] 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 esier. [0096] In other embodiments, the invention is directed to pharmaceutical compositions, comprising: a. at least compound of formula I or pharmaceutically acceptable salt thereof; and b. at least one pharmaceutically acceptable carrier. Generally, the compound of formula I or a pharmaceutically acceptable salt thereof will be present at a level of from about 0.1%, by weight, to about 90% by weight, based on the total weight of the pharmaceutical composition, based on the total weight of the pharmaceutical composition. Preferably, the compound of formula I or a pharmaceutically acceptable salt thereof will be present at a level of at least about 1 %, by weight, based on the total weight of the pharmaceutical composition. More preferably, the compound of formula I or a pharmaceutically acceptable salt thereof will be present at a level of at least about 5%, by weight, based on the total weight of the pharmaceutical composition. Even more preferably, the norepinephrine 29 WO 2005/037207 PCT/US2O04/033730 reuptake inhibitor or a pharmaceutically 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 pharmaceutically acceptable salt thereof will be present at a level of at least about 25%, by weight, based on the total weight of the pharmaceutical composition. [0097] 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). Pharmaceutically acceptable carriers are those that are compatible with the other ingredients in the formulation and biologically acceptable. [0098] 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 contain up to 99% of the active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvmylpyrrolidine, low melting waxes and ion exchange resins: [0099] 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 30 WO 2005/037207 PCT/US2004/033730 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 carboxymethy! 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. [0100] 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. [0101] 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 capsule or tablet itself, or it can be the appropriate number of any such compositions in package form. [0102] 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. [0103] The one or more other pharmaceutical active agents may be administered in a therapeutically effective amount simultaneously (such as individually at the 31 WO 2005/037207 PCT/US2004/033730 same time, or together in a pharmaceutical composition), and/or successively with one or more compounds of the present invention. [0104] 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 fxample 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. [0105] 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 be concurrent or simultaneous. [0106] It is believed that the present invention described presents a substantial breakthrough in the field of treatment, alleviation, inhibition, and/or prevention of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, 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. [0107] 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 stap of: administering to said subject an effective amount of a compound of formula I 32 WO 2005/037207 PCT/US2OO4/03373O 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. [0108] "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. [0109] 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. [0J10] The term "sexual dysfunction" includes, but is not limited to, condition relating to desire and/or arousal. [0111] 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 urethra! 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). 33 WO 2005/037207 PCT/US2004/033730 [0112] 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. [0113] 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. [0114] 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 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 34 WO 2005/037207 PCT/US2O04/03373O 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). [0115] In one embodiment, the present invention is directed to methods for treating or preventing vasomotor symptoms in a subject in need thereof, comprising the step of: administering to said subject an effective amount of at least one compound of formula I or pharmaceutically acceptable salt thereof. [0116] 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 hypothaiamus may activate the descending autonomic pathways and result in heat dissipation via vasodilation and sweating (hot flush) (Figure 1). Accordingly, the estrogen deprivation may result in altered norepinephrine activity. [0117] Norepinephrine synthesized in perikarya of the brainstem is released at the nerve terminals in the hypothaiamus and brainstem. In the hypothaiamus, NE regulates the activity of neurons residing in the thermoregulatory center. In the brainstem. NE innervates serotoninergic neurons (5HT), and acting via adrenergica1 and adrenergiCa2 postsynaptic receptors, it stimulates the activity of the serotoninergic system. In response, 5-HT neurons also modulate the activity the thermoregulatory center and feedback to NE neurons. Via this feedback connection, 5-HT, acting via 5-HT2a receptors, inhibit the activity of NE neurons. Norepinephrine in the synaptic cleft is also taken up by NE transporter (NET) located in NE neurons. The transporter recycles NE and makes it available for multiple neurotransmission 35 WO 2005/037207 PCT/US2O04/03373O (Figure 2). [0118] The present invention provides a treatment for vasomotor symptoms by methods of recovering the reduced activity of norepinephrine. Ncrepinephrine 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 aarenergic 02 receptor with an antagonist, or (iii) blocking the activity of 5-HT on NE neurons with a 5-HT2a antagonist. [0119] 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. [0120] 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. [0121] 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. [O1221 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 o r pharmaceutically acceptable salt thereof. 36 WO 20(15/037207 PCT/US20fl4/03373(> [0123] In another embodiment, the present invention is directed to methods for treatiricf^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. [0124] 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 pharmaceuticaily acceptable salt thereof. [0125] 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. [0126] Examples of pain that can be acute or chronic and that can be treated in accordance with the methods of the present invention include inflammatory pain, musculoskeletal pain, bony pain, lumbosacral pain, neck or upper back pain, visceral pain, somatic pain, neuropathic pain, cancer pain, pain caused by injury or surgery such as burn pain or dental pain, or headaches such as migraines or tension headaches, or combinations of these pains. One skilled in the art will recognize that these pains may overlap one another. For example, a pain caused by inflammation may also be visceral or musculoskeletal in nature. [0127] 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 37 WO 20(15/037207 PCT/US2 and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolodine. [0163] In an analogous manner to Example 1, step 2 142-f(35)-3-aminopyrrolidin-1 -yl]-1 -(3-chlorophenyl)ethvncvclohexanol 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]ethyi}cyclohexanol dihydrochloride 60 WO 2005/037207 PCT/US2004/033730 [0164] In an analogous manner to Example 1, step 1 fert-butyl (1 -ff3-chlorophenyl)(1 -hydroxvcvclohexyl)acetvnpiperidin-4-vl)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. [0165] In an analogous manner to Example 13, step 2 1 -(1 -(3-chlorophenylV2-f4-(methvlamino)piperidin-i-vr)ethvl)cyclohexanol dihydrochloride was prepared from tert-butyl {1-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS m/z 351/353 ([M+Hf); HRMS: calcd for C2oH31CIN20 • 2.00 HCI, 422.1658; found (ESI)] 351.2208. Example 18: 1-[2-(4-aminopiperidin-1-yl)-1-(3-bromophenyl)ethylJcyclohexanol dihydrochloride [0166] In an analogous manner to Example 1, step 1 te/t-butyl (1-f(3-bromophenyl)(1-hydroxycyclohexvl)acetyflpiperidin-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. [0167] In an analogous manner to Example 13, step 2 tert-butyl (1-f2-(3- bromophenyO-2-(1-hvdroxycyclohexvl)ethvnpiperidin-4-vl)carbamate was prepared from 61 WO 2005/037207 PCT/US2004/03373(I f ert-birtyl {1 -[(3-bromophenylphenyl)(1 -hydroxycyclohexyI)acetyl]piperidin-4- yl}carbamate. MS (ES) m/z 481.3 ([M+H]+); HRMS: calcd for C24H37BrN2O3, 480.1988; found-fESI), 481.2081. [0168] In an analogous manner to Example 14, 1 -f2-(4-aminopiperidin-1 -vlV1 -(3-bromophenyliethyncyclohexanol dihydrochloride was prepared from ferf-butyl {1-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyi)ethyi]piperidin-4-yl}carbamate. HRMS: calcd for C-,9H29BrN2O • 2.00 HCI, 452.0997; found (ES!), 381.1525. Example 19:1 -{1 -(3-bromophenyl)-2-[4-(methylarnino)piperidin-1 -yljethyljcyclohexanol dihydrochloride [0169] In an analogous manner to Example 1, step 1 tert-butyl (1-f(3-bromophenvl)(1-hydroxycyclohexyl)acetyflpiperidin-4-yl)carbamate was prepared from {3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-N-boc-aminopiperidine. MS (ES) m/z 495.2 ([M+H]+); HRMS: calcd for C24H35BrN2O4, 494.1780; found (ESI), 495.1864. [0170] In an analogous manner to Example 13, step 2 1-{1-(3-bromophenyl)-2-[4-(methylamino)piperidtn-1-yl]ethyl}cyclohexanol dihydrochloride was prepared from tert-butyl {1 -[(3-bromophenylphenyl)(1 -hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS (ESI) m/z 395 ([M+H]+); HRMS: calcd for C2oH31BrN20 • 2.00 HCI, 466.1153; found (ESI), 395.1708. Example 20: 1-{2-(1,4'-bipiperidin-1'-yl)-1-[3-(trifluoromethyI)phenyl]ethyl}cyclohexanol dihydrochloride 62 WO 2005/037207 PCT/US2004/033730 [0171] In an analogous manner to Example 1, step 1 1-(2-(1,4'-bipiperidin-1'-vl)-1-r3-(trif)uoromethyl)phenvn-2-oxoethvl)cvc)ohexanol was prepared from (1-hydroxycyc!ohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and N-(4-piperidine)piperidine. [0172] In an analogous manner to Example 1, step 2 1-{2-(1,4'-bipiperidin-1'-vO-1-r3-(trifluoromethvDphenvllethvDcvclohexanol dihvdrochloride 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-vlethvllcvclohexanol dihvdrochloride [0173] In an analogous manner to Example 1, step 1 te/1-butvl 4-f(1- hvdroxvcvclohexvlK1-naphthvl)acetvflpiperazine-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. [0174] In an analogous manner to Example 1, step 2 1-H-(1-naphtr)vl)-2-piperazin-1-ylethvlicyclohexanol dihvdrochloride was prepared from terf-butyl 4-[(1-hydroxycyclohexyl)(1-naphthyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 339 QM+H]+); HRMS: calcd for C22H30N2O • HCI, 374.2125; found (ESLFT), 339.24268. 63 WO 2005/037207 PCT/US2004/033730 Example 22:1-[2-(1,4'-bipipendin-r-yl)-i-(2-naphthyl)ethyi]cyciohexanol dihydrochloride [0175] In an analogous manner to Example 1, step 1 1 -[2-(1,4'-bipiperidin-1 '-vl)-1 -(2-naphthvO-2-oxoethvHcyclohexanol was prepared vfrom (1-hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and N-(4-piperidine)piperidine. [0176] In an analogous manner to Example 1, step 2 1-[2-(1,4'-bipiperidin-1'-yf)-1-(2-naphthyl)ethyl]cyclohexano! dihydrochloride was prepared from 1-[2-(1,4'-bipiperidin-1'-yl)-1-(2-naphthyl)-2-oxoethyl]cyclohexano). MS m/z 421 ([M+H]+); HRMS: calcd for C28H40N2O ¦ 2.00 HCI, 492.2674; found (ESI), 421.3224. Example 23:1-{2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride [0177] In an analogous manner to Example 1, step 1 terf-butyl 4-f(1- hvdroxvcvclohexvnf3-(trifluoromethoxv)phenvl1acetvl)piperazine-1-carboxvlate was prepared from (1~hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1-f) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C24H33F3N2O5, 486.2342; found (ESI), 487.2398. [0178] In an analogous manner to Example 1, step 2 1 -(2-piperazin-1 -yl-1 -F3-(trifluoromethoxy)phenynethvl)cyclohexanol dihydrochloride was prepared from tert-butyl 64 WO 2005/037207 PCT/US2004/033730 4-{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyI]acetyl}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}cyclohexanotdihydroch!oride [0179] 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 ths combined organic extracts were dried over magnesium sulfate and concentrated to yield 442 mg (72%) 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenylJethyl}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-methy!piperazin-1 -yl)-1 -[3-(trifluoromethoxy)phenyl]ethy!}cyc!ohexanol 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 65" W O 20(15/037207 PCT/US2O(M/03373H [0180] In an analogous manner to Example 1, step 1 ferf-butyi (1-r(3-bromo-4-methoxvphenvl)(1-hydroxvcvcio'nexvl')acetvlipiperid}n-4-vl)carbamate was prepared from (3-bromo-4-methoxyphenyl)(1-hydroxycyclohexyI)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. [0181] In an analogous manner to Example 13, step 2 ferf-butyl {1-[2-(3-bromo-4-methoxypheny!)-2-(1 -hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate was prepared from tert-buty\ {1 -[(3-bromo-4-methoxyphenyl)(1 -hydroxycyclohexyl)acetyl]piperidin-4-yl]carbamate. MS (ES) m/z 511.4 ([M+H]+); HRMS: calcd for CgsHagBrNsCU, 510.2093; found (ESI), 511.2147. [0182] In an analogous manner to Example 14, 1-[2-(4-aminopiperidin-1-yl)-1-(3-bromo-4-methoxypheny!)ethyl]cyc!ohexano! dihydrochloride was prepared from tert-butyl {1 -[2-(3-bromophenyl)-2-(1 -hydroxycyclohexyl)ethy!]piperidin-4-y!}carbamate. MS m/z411/413 ([M+H]+); HRMS: calcd for C2oH31BrN202 • 2.00 HCI, 482.1102; found (ESI), 411.1656. Example 26: 1-{2-(4-pyrrolidin-1-ylpiperidin-1-yl)-1-[3-(trifluoromethy!)phenyl]ethyl}cyclohexanol dihydrochloride [0183] In an analogous manner to Example 1, step 1 1 -(2-(4-pyrrolidin-1 -vlpiperidin-1 -vl)-'l-[3-(trifluoromethvl)phenvn-2-oxoetnyl)cvclohexanol was prepared from (1- ' 66 WO 2005/037207 PCT/US2004/033730 hydroxycyclohexyl)[3-(trifluoromethyl)phenyi]acetic acid (Reference Example 1-m) and 4-(1 -pyrrolidinyl)piperidine. [0184] In an analogous manner to Example 1, step 2 1-{2-(4-pyrrolidin-1-ylpiperidin-1-yl)-1-[3-(trtfluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride was prepared from 1-{2-(4-pyrrolidin-1-ylpiperidin-1-yl)-1-[3-(trifiLioromethyl)phenyi]-2-oxoethy[}cyclohexanol. MS m/z 425 ([M+H]+); HRMS: calcd for C24H35F3N2O • 2.00 HCl, 496.2235; found (ESI), 425.2789. Example 27:1-{1 -[4-(benzyloxy)phenyl]-2-piperazin-1-y!ethy!}cyclohexanol dihydrochloride [0185] In an analogous manner to Example 1, step 1 te/f-butyl 4-ff4- (benzvloxy)phenvlK1-hvdroxycyclohexvl)acetvl|piperazine-1-carboxylate was prepared from (4-benzyloxyphenyl)(1-hydroxycyclohexy5)acetic acid (Reference Example 1-n) and tert-butyl 1 -piperazinecarboxylate. MS (ESI) m/z 509 ([M+H]+); HRMS: caicd for C3oH4oN205) 508.2937; found (ESI), 509.3027. [0186] In an analogous manner to Example 1, step 1-{1-[4-(benzyloxy)phenylj-2-piperazin-1-ylethyl}cyclohexanol dihydrochloride was prepared from fe/f-butyl 4-[[4-(benzyloxy)phenyl](1-hydroxycyclohexyl)acetyl]piperazine-1 -carboxylate. HRMS: calcd for C25H34N2O2 • 2.00 HCl, 466.2154; found (ESI), 395.2683. Example 28: 1 -{2-piperazin-1 -yl-1 -[4-(trif!uoromethoxy)phenyl]ethyl}cyclohexanoI dihydrochloride 67 WO 2005/037207 PCT/US2004/033730 [0187] In an analogous manner to Example 1, step 1 ferf-butyl 4-((1- hvdroxvcvclohexvl)[4-(trif)uoromethoxv)phenvl]acetyl)piperazine-1-carboxvlate was prepared from (1-hydroxycyclohexyl)[4-(trif!uoromethoxy)phenyl]acetic acid (Reference Example 1-g) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z487 ([M+H]+). [0188] In an analogous manner to Example 1, step 2 1-{2-piperazin-1-yl-1-[4-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride was prepared from terf-butyl 4-{(1-hydroxycyclohexyl)[4-(trifIuoromethoxy)phenyl]acetyl}piperazine-1-carboxyIate. MS m/z 373 ([M+H]+); Anal. Calcd-for dgHayFaNzOa • 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-methoxyphenyI)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride [0189] In an analogous manner to Example 1, step 1 tetf-butyl (1-f(3-bromo-4-methoxvphenyl)fi-hvdroxvcvclohexvl)acetvnpiperidin-4-vl)carbamate was prepared from (3-bromo-4-methoxyphenyl)(1-hydroxycyclo^lexyl)acetic acid (Reference Example 1-1) and 4-N-boc-aminopiperidine. MS (ES) m/z 525.2 ([M+H]+); HRMS: calcd for CzsHarBrNzOs, 524.1886; found (ESI), 525.1971. [0190] In an analogous manner to Example 13, step 2 1-{1-(3-bromo-4- methoxyphenyl)-2-[4-(methylamino)piperidin-1-yI]ethyl}cyclohexanol dihydrochloride was prepared from fe/t-butyl {1-[(3-bromo-4-methoxyphenyl)(1- f>8 WO 2005/037207 PCT/US2OO4/033730 hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS (ESI) m/z 425 ([M+H]+); HRMS: calcd for C2iH33BrN2O2 " 2.00 HCI, 496.1259; found (ESI), 425.1793. EExample 30:1-{2-[4-(methylamino)piperidin-1-yi]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanoldihydrochloride [0191] In an analogous manner to Example 1, step 1 tert-butyl (1-{(1- hvdroxvcvclohexvl)[3-(trifluoromethvl)phenvnacetvl}piperidin-4-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetic acid (Reference Example 1-m) and 4-N-boc-aminopiperidine. MS (ES) m/z 485.3 ([M+H]+); HRMS: calcd for C25H35F3N2O4, 484.2549; found (ES!), 485.2612. [0192] In an analogous manner to Example 13, step 2 1-{2-[4-(methylamino)piperidin- 1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride was prepared from tert-butyl (1 -{(1 -hydroxycyclohexyl)[3-(trifluoromethyl)phenyl]acetyl}piperidin-4- yl)carbamate. MS m/z 385 ([M+H}+); HRMS: calcd for C21H31F3N2O ¦ 2.00 HCI, 456.1922; found (ESI), 385.2454. Example 31: 1-[1-(2-naphthyl)-2-(4-pyrroIidin-1-ylpiperidin-1-yl)ethyl]cyclohexanol dihydrochloride [0193] In an analogous manner to Example 1, step 1 1 -M-(2-naphthyl)-2-(4-pyrrolidin-1 -ylpiperidin-1 -vl)-2-oxoethvl]cyclohexanol was prepared from (1 -hydroxycyclohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and 4-(1-pyrrolidinyl)piperidine. 69 WO 2005/037207 PCT/US2MU/H33730 [0194] In an analogous manner to Example 1, step 2 1-[1-(2-naphthyl)-2-(4-pyrro!idin-1-ylpip@ridin-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 [0195] In an analogous manner to Example 1, step 1 ferf-butvl (1-IY1- hvdroxvcvclohexyl)(2-naphthvnacetvnpiperidin-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 CasHasN^, 466.2832; found (ESJ), 467.2902. [0196] In an analogous manner to Example 13, step 2 terf-butvl f1-f2-(1- hvdroxvcvclohexylV2-(2-naphthyl)ethyflpiperidin-4-yl)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. [0197] In an analogous manner to Example 14, 1-[2-(4-aminopiperidin-1-y!)-1-(2-naphthyl)ethyl]cyclohexanol dihydrochloride was prepared from tert-bu\y\ {1-[2-(1-hydroxycyclohexyl)-2-(2-naphthyl)ethyl]piperidin-4-yl}carbamate. MS m/z 353 ([M+H]+); HRMS: calcd for C23H32N2O • 2.00 HCI, 424.2048; found (ESI), 353.2598. Example 33: 1 -[2-[(3-chlorobenzy!)amino]-1 -(2-naphthyl)ethyl]cyclohexanol hydrochloride 70 WO 2005/037207 PCT/US2004/033730 [0198] In an analogous manner to Example 1, step 1 N-(3-chlorobenzvlV2-(1 -hydroxvcvclohexvO-2-f2-naphthyl)acetamicie was prepared from (1-hydroxycyc!ohexyl)(2-naphthyl)acetic acid (Reference Example 1-q) and 3-chlorobenzylamine. MS (ESI) m/z408/410 ([M+H]+). [0199] !n an analogous manner to Example 1, step 2 1-[2-[(3-chlorobenzyl)amino]-1-(2~naphthy!)ethyl]cyclohexanol hydrochloride was prepared from A/-(3-chlorobenzyl)-2-(1-hydroxycyclohexy!)-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-pyrrolidint1-ylethy!]cyclohexanol hydrochloride [0200] In an analogous manner to Example 1, step 1 1 -[1 -(3-chlorophenvD-2-oxo-2-pvrrolidin-1-ylethvricvclohexanol was prepared from (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and pyrroiidine. MS (ESI) m/z 322/324 ([M+H]+); HRMS: calcd for C18H24C1NO2, 321.1496; folind (ESLFT), 322/15603. [0201] In an analogous manner to Example 1, step 2 1-[1-(3-chlorophenyl)-2-pyrrolidin-1-ylethyl]cyc!ohexanol hydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-oxo-2-pyrrolidin-1-ylethyl]cyclohexanol. HRMS: calcd for C18H26CINO - HCI, 343.1470; found (ESI_FT), 308.17736. 71 WO 2005/037207 PCT/US2004/033730 Example 35: 1-[2-(4-aminopiperidin-1-yl)-1-(3-chlorophenyl)ethy!]cyclohexano! dihydrochloride [0202] In an analogous manner to Example 1, step 1 fe/f-butyl f1-[Y3-chlorophenvl)n-hvdroxvcvclohexv0acetvnpiperidin-4-vl)carbamate was prepared from (3-ch!orophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a} and 4-N-boc-aminopipendine. MS m/z 451/453 ([M+Hf); HRMS: calcd for C24H35CIN2O4l 450.2285; found (ESI), 451.2353. [0203] In an analogous manner to Example 13, step 2 1-[2-(4-aminopiperidin-1-yl)-1-(3-chloropheny!)ethy!]cyclohexanol dihydrochloride was prepared from terf-butyl {1-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS m/z 337/339 ([M+H]+); HRMS: calcd for C19H29CIN2O • 2.00 HCl, 408.1502; found (ESI), 337.2022 Exa mple 36:1 -{1 -(3-chlorophenyl)-2-[4-(dimethylamino)piperidin-1 -yl]ethyl}cyclohexanol dihydrochloride [0204] A solution of 1-[2-(4-aminopiperidin-1-yi)-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 72 WO 2005/037207 PCT/US2004/033730 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-chlorophBnyl)-2-[4-(dimethylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride as a white solid. HRMS: calcd for C21H33CIN2O • HC1, 400.2048; found (ESI), 365.2349. Example 37: 4-[1 -(3,4-dichlorophenyl)-2-piperazin-1 -ylethyl]-1 -methy!piDeridin-4-o! trihydrochloride [0205) In an analogous manner to Example 1, step 1 ferf-butyl 4-f(3.4- dichlorophenvl)(4-hvdroxv-1-methvlpiperidin-4-vnacetvnpiperazine-1-carboxylate was prepared from (3,4-dichlorophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-i) and tert-buty! 1-piperazinecarboxylate. HRMS: calcd for CasHssClaNaO^ 485.1848; found (ESI_FT), 486.19305. [0206] In an analogous manner to Example 1, step 2 4-[1-(3,4-dichlorophenyl)-2-piperazin-1-yIethyl]-1-methylpiperidin-4-oI trihydrochloride was prepared from fe/t-butyl 4-[(3,4-dichlorophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetyl]piperazine-1-carboxylate. HRMS: calcd for C18H27Cl2N3O • 3.00 HCI, 479.0831; found (ESLFT), 372.16065. Example 38: 1-[2-(benzylamino)-1-(3,4-dichlorophenyl)ethyl]cyclohexanol hydrochloride [0207] In an analogous manner to Example 1, step 1 /V-benzyl-2-(3.4-dichlordphenvO-2-(1-hydroxvcvclohexyl)acetamide was prepared from 3,4-dichIoro-alpha-(1- 73 WO 2005/037207 PCT/US2004/033730 hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and benzylamine. HRMS: calcd for C2iH23CI2NO2f 391.1106; found (ESLFT), 392.11598. [0208] 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)acetarnide. HRMS: calcd for C21H25CI2NO • HCI, 413.1080; found (ESLFT), 378.13864. Example 39: 1 -{2-(4-aminopiperidin-1 -yl)-1 -[3-(trifluoromethyl)pheny!]ethy!}cyclohexanol dihydrochloride [0209] In an analogous manner to Example 1, step 1 tetf-butvl (1-1(1- hvdroxvcvclohexvnf3-(trifluoromethvl)phenvllacetvl)piperidin-4-vl)carbamate was prepared from (1-hydroxycyclohexylj[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. [0210] In an analogous manner to Example 13, step 2 terf-butyl (1-(2-(1- hvdroxvcvclohexvl)-2-f3-(trifluoromethvl)phenynethvl)piperidin-4-vl)carbamate was prepared from terf-butyl (1-{(1-hydroxycyclohexyl)[3- (trifluoromethyl)phenyl]acetyl}piperidin-4-yI)carbamate. MS (ES) m/z 471.4 ([M+H]+); HRMS: calcd for C2SH37F3N2O3, 470.2756; found (ESI), 471.2852. [0211] In an analogous manner to Example 14, 1-{2-(4-aminopiperidin-1-yl)-1-[3-(tnfluoromethyl)phenyl]ethyl}cyclohexanol dihydrochloride was prepared from tert-butyl (1-{2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethyl)phenyl]ethyl}piperidin-4-yl)carbamate. MS m/z 371 ([M+H]+); HRMS: calcd for C2oH?gF3N20 • 2.00 HCI, 442.1766; found (ESI), 371.2309. 74 Example 40:1-[2-(benzylamino)-1-(3-brornophenyl)ethyl]cyciobutanol hydrochloride [0212] In an analogous manner to Example 1, step 1 A/-benzvl-2-(3-bromophenvP-2-(1 -hydroxycyclobutvDacetamide was prepared from (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and benzylamine. HRMS: calcd for C19H2oBrN02, 373.0677; found (ESIJ=T), 374.07415. [0213] in an analogous manner to Example 1, step 2 1-[2-(benzy!amino)-1-(3-bromophenyl)ethyl]cyclobutanol hydrochloride was prepared from /V-benzy!-2-(3-bromophenyl)-2-(1-hydroxycyclobutyl)acetamide. HRMS: calcd for C-i9H22BrNO • HCI, 395.0652; found (ESI_FT), 360.09546. Example 41: 1-[2-(benzyIamino)-1-(3-chlorophenyl)ethyl]cyclohexanol hydrochloride [0214] In an analogous manner to Example 1, step 1 /V-benzvl-2-(3-chlorophenyl}-2-(1 -hydroxycyclohexyDacetamide was prepared from (3-chlorophenyl)(1-hydroxycyc!ohexyl)acetic acid (Reference Example 1-a) and benzylamine. HRMS: calcd for C2iH24CINO2, 357.1496; found (ESI_FT), 358.15607. [0215] In an analogous manner to Example 1, step 2 1-[2-(benzylamino)-1-(3-chlorophenyl)ethyl]cyclohexanol hydrochloride was prepared from /V-benzyl-2-(3- 75 WO 2005/037207 PCI7US2004/033730 chlorophenyl)-2-(1-hydroxycyclohexyl)acetamide. HRMS: calcd for C2iH26CINO • HCI, 379.1470; found (ESi_FT), 344.17761. Example 42:1 -[2-(cyclohexylamino)-1 -(3,4-dichlorophenyl)ethyl]cyclohexanol hydrochloride [0216] In an analogous mariner to Example 1, step 1 A/-cvclohexvl-2-(3,4- dichlorophenvl)-2-(1-hvdroxvcvclohexyl)acetamide was prepared from 3,4-dichloro-alpha-(1-hydroxycyclohexy!)benzeneacetic acid (Reference Example 1-d) and cyclohexylamine. MS (ESI) m/z 384/386/388 ([M+H]4). [0217] In an analogous manner to Example 1, step 2 1-[2-(cyclohexylamino)-1-(3,4- dichlorophenyl)ethyl]cyclohexano! hydrochloride was prepared from /V-cyclohexyl-2-(3,4- dich!orophenyi)-2-(1-hydroxycyc!ohexyl)acetamide. MS (ESI) m/z [M+H]+ (370/372/374); HRMS: calcd for C20H29CI2NO • HCI, 405.1393; found (ESI), 370.1687; Anal. Calcd for C2oH29C!2NO • 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-y[)-1-(1-naphthyI)ethyl]cyclobutano( dihydrochloride [0218] In an analogous manner to Example 1, step 1 tert-butyl (1-f(1- hvclroxvcvclobutvn(1-naphthvnacetvllpiperidin-4-yl)carbamate was prepared from (1- 76 WO 2005/037207 PCT/US2004/033730 hydroxycyclobutyl)(1-naphthyi)acetic acid (Reference Example 1-o) and 4-N-boc-aminopiperidine. MS (ES) m/z 439.3 ([M+H]+). [0219] In an analogous manner to Example 1, step 2 1-[2-(4-aminopiperidin-1-yl)-1-(1-naphthyl)ethyl]cyclobutano! dihydrochloride was prepared from terf-butyl (1-[(1-hydroxycyclobutyl)(1-naphthyl)acetyl]piperidin-4-y!}carbamate. MS (ES) m/z 325.3 ([M+H]+); HRMS: calcd for C2iH28N2O • 2.00 HCI, 396.1735; found (ESI), 325.2272. Eixample44: 4-[2-(benzylamino)-1-(3-bromophenyl)ethyl]-1-methylpiperidin-4-ol dihydrochloride [0220] In an analogous manner to Example 1, step 1 /V-benzvl-2-(3-bromophenvO-2-(4-hvdroxv-1-rnethvlpiperidin-4-yl)acetamide was prepared from (3-bromophenyl)(4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-r) and benzylamine. HRMS: calcd for C2iH25B'rN2O2, 416.1099; found (ESI_FT), 417.11652. [0221] 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-bromophenyi)-2-(4-hydroxy-1-methylpiperidin-4-yl)acetamide. HRMS: calcd for C2iH27BrN2O " 2.00 HCI, 474.0840; found (ESI_FT), 403.13802. Example 45: 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclopentanol dihydrochloride 77 WO 2005/037207 PCT/US2004/033730 [0222] In an analogous manner to Example 1, step 1 fert-butvl 44(1- hydroxvcyclopentvDf 1 -naphthvPacetyDpiperazine-i-carboxvlate was prepared from (1-hydroxypyclopentyl)(1-naphthyl)acetic acid (Reference Example 1-s) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 439 ([M+Hf); HRMS: calcd for C26H34N0O4, 438.2519; found (ESI), 439.2563. [0223] In an analogous manner to Example 1, step 2 1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclopentanoi 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 [0224] In an analogous manner to Example 1, step 1 tert-butvl 4-U1- hvdroxvcvclobutvl)r3-(trifluoromethoxv)phenvnacetyl)piperazine-1-carboxvlate 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. [0225] In an analogous manner to Example 1, step 2 1-{2-piperazin-1-yl-1-[3-(tnf!uoromethoxy)phenyl]ethyl}cyclobutanol dihydrochloride was prepared from tert-butyl 4-{(1-hydroxycyclobutyl)[3-(trifluoromethoxy)phenyl]acetyl}piperazine-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 78 WO 2005/(137207 PCT/US2004/033730 [0226] In an analogous manner to Example 1, step 1 /V-f4-fluorobenzv!)-2-(1-hvdroxvcvclohexvl)-2-f3-(trifluoromethyl)phenvnacetamide was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethy!)phenyl]acetic acid (Reference Example 1-m) and 4-fluorobenzylamine. MS (ESI) m/z 410 ([M+H}+). [0227] In an analogous manner to Example 1, step 2 1-{2-[(4-fluorobenzyl)amino]-1-[3-(trifluorornethyl)phenyl]ethyl}cyclohexanol hydrochloride was prepared from A/-(4-fluorobenzy!)-2-(1 -hydroxycyclobexyl}-2-[3-(trifluoromethyl)pheny!]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-(cycIohexylamino)ethyl]cyclohexanol hydrochloride [0228] In an analogous manner to Example 1, step 1 2-(3-bromophenvl)-/V-cyclohexyl-2-(1-hydroxvcyclohexvl)acetamide was prepared from (3-bromophenyl)(1-hydroxycyc!ohexy!)acetic acid (Reference Example 1-b) and cyclohexylamine. MS (ESI) m/z 394/396 ([M+H]+). [0229] In an analogous manner to1 Example 1, step 2 1-[1-(3-bromophenyl)-2- (cyc!ohexy!amino)ethyl]cyc!ohexanol hydrochloride was prepared from 2-(3-bromophenyl)-A/-cyclohexyl-2-(1-hydroxycyclohexy!)acetamide. MS (ESI) m/z 380/382 ([M+Hj-"); HRMS: calcd for C20H3oBrNO • HCI, 415.1278; found (ESI), 380.1574. 79 WO 2005/037207 PCT/US2004/033730 Example 49:1 -[2-[4-(methylamino)piperidin-1 -yl]-1 -(2-naphthyl)ethyl]cyclohexanol dihydrochloride [0230] In an analogous manner to Example 1, step 1 te/t-butvl (1-fd- hvdroxvcvclohexvl)(2-naphthvl)acetvnpiperidin-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+H]+); HRMS: calcd for C28H38N2O4, 466.2832; found (ESI), 467.2902. [0231] 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 te/f-butyl {1-[(1-hydroxycyclohexyl)(2-naphthyl)acetyi]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-piperazin-1-ylpentan-3-ol dihydrochloride [0232] In an analogous manner to Example 1, step 1 fetf-butyl 4-r2-(3-bromophenvQ-3-ethvl-3-hvdroxvpentanovHp?perazine-1-carboxylate was prepared from 2-(3-bromophenyl)-3-ethyl-3-hydroxypentanoic acid (Reference Example 1-t) and tert-butyl 1-piperazinecarboxylate. MS (ESI) /77/z>469/471 ([M+HD; HRMS: calcd for C22H33BrN2O4) 468.1624; found (ESI_FT). 469.17071. 80 WO 2005/037207 PCTYUS20butyl-1 -hydroxycyclohexyl)acetic acid (Reference Example 1-bb) and A/-methyIpiperazine. MS (ESI) m/z 481/483 ([h/l+H]+). [0275] In an analogous manner to Example 1, step 2 1 -[1 -(3-brorno-4-methoxyphenyl)- "2-(4-methylpiperazin-1-yl)ethyl]-4-te/r-butylcyclohexanol dihydroch/oride was prepared from te/t-butyl 1 -[1 -(3-bromo-4-methoxyphenyl)-2-(4-methylpiperazi n-1 -yl)-2-oxoethyl]-4- ferf-butylcyclohexanol. MS (ESI) m/z 467/469 ([M+H]+); HRMS: caJcd for C24H39BrN2O2 2.00 HCI, 538.1728; found (ESI), 467.2258. Example 74: 2-[1-(3-chlorophenyl)-2-piperazin-1-yIethyl]decahydronaphthalen-2-ol dihydrochloride [0276] In an analogous manner to Example 1, step 1 fert-buty!4-[1-(3-chlorophenylphenyl)f2-hvdroxydecahvdronapthvl)acetvnpiperazine-1 -carboxylate was prepared from (3-chloropheny!)(2-hydroxydecahydronapthyl)acetic acid (Reference Example 1-cc) and te/t-butyl 1-piperazinecarboxylate. MS (ESI) m/z 491/493 ([M+H]+). [0277] In an analogous manner to Example 1, step 2 2-[1-(3-chlorophenyl)-2- piperazm-1-ylethyl]decahydronaphthalen-2-ol dihydrochloride was prepared from tert- butyl 4-[1-(3-chlorophenylphenyl)(2-hydroxydecahydronapthyI)acetyl]piperazine-1- 93 WO 2005/037207 PCT/US20U4/03373U carboxylate. 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 [0278] In an analogous manner to Example 1, step 1 2-(3.4-dichlorophenyl)-2-(1 -hydroxvcycloriexvl)-A/-[4-(trifluoromethvl)benzvllacetamide was prepared from 3,4-dichloro-aipha-(1-hydroxycyclohexyl)benzeneacetic acid (Reference Example 1-d) and -4-trifluoromethylbenzylamine. MS (ESI) m/z460/462/464 ([M+H]+). [0279] In an analogous manner to Example 1, step 2 1-(1-(3,4-dichlorophenyl)-2-{[4-(trifluoromethy!)benzyl]amino}ethyi)cyc!ohexanol hydrochloride was prepared from 2-(3,4-dichlorophenyl)-2-(1-hydroxycyclohexyl)-A/-[4-(trifluoromethyl)benzyJ]acetamide. MS (ESI) m/z 446/448/450 ([M+H]+); HRMS: calcd for C22H24CI2F3NO • 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-fe/t-butyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0280] In an analogous manner to Example 1, step 1 tert-butyl 4-\(4-tert-buivl-1-hvdroxvcvclohexvn(1-naphthvnacetvl1piperazine-1-carboxylate was prepared from (4- 94 WO 2005/037207 PCT/US2004/033730 terf-buty!-1-hydroxycyc!ohexyl)(1-naphthyl)acetic acid (Reference Example 1-dd) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z509 ([M+H]+); HRMS: calcd for C3iH44Np4, 508.3301; found (ESI), 509.3354. [0281] in an analogous manner to Example 1, step 2 4-terf-butyI-1-[1 -(1-naphthyi)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from tenf-butyl 4-[(4-fcrf-bufyi-1-hydroxycyclohexyl)(1-naphthy!)acetyl]piperazine-1-carboxy!ate. MS (ESI) m/z 395 ([M+H]+); HRMS: calcd for C26H3aN2O • 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 [0282] In an analogous manner to Example 1, step 1 terf-butvl 4-f(3-chiorophenvlH4-hvdroxytetrahvdro-2H-pvran-4-vl)acetvnpiperazine-1-carboxvlate was prepared from (3-chlorophenyl)(4-hydroxytetrahydro-2H-pyran-4-y!)acetic acid (Reference Example 1-ee) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z439/441 ([M+H]+); HRMS: calcd for C22H3iCIN2Os, 438.1921; found (ES!_FT), 439.19884. [0283] In an analogous manner to Example 1, step 2 4-[1-(3-chlorophenyl)-2- p!perazin-1-ylethy!]tetrahydro-2H-pyran-4-ol dihydrochloride was prepared from tert- butyl 4-[(3-chlorophenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetyI]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)ethy!]tetrahyd ro-2H-pyran-4-oi dihydrochloride 95 WO 2005/037207 PCT/US2004/033730 [0284] In an analogous manner to Example 24, 4-[1-{3-chiorophenyl)-2-(4- methylpiperazin-1-yl)ethy!]tetrahydro-2H-pyran-4-ol dihydrochloride was prepared from 4-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]tetrahydro-2/V-pyran-4-oI (see Example 77). MS (ESI) m/z 339 ([M+H]+);-HRMS: calcd for dsHayCINaOs " 2.00 HCI, 410.1295; found (ESI), 339.1844. Example 79: 1 -[1 -(3-bromophenyl)-2-(4-methylpiperazin-1 -yl)ethyl}-4-terf-butylcyclohexanol dihydrochloride [0285] In an analogous manner to Example 1, step 1 1 -f 1 -C3-bromophenvl)-2-(4-methv[pipera2in-1-vl)-2-oxoethvll-4-terf-butylcvclohexanol was prepared from (3-' bromophenyl)(4-terf-butyl-1-hydroxycyclohexyl)aceticacid (Reference Example 1-ff) and A/-methylpiperazine. MS (ESI) m/z451/453 ([M+H]+). [0286] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2-(4-methylp)perazin-1-yl)ethyl]-4-ferf-butylcyclohexanol dihydrochloride was prepared from 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)-2-oxoethyl]-4-ferf-butylcyclohexanol. MS (ESI) m/z 437/439 «M+H]+); HRMS: calcd for CzzHZ7BrH2O " 2.00 HCI, 508.1623; found (ESI), 437.2154. Example 80:1-{1 -(3,4-dich!oropheny!)-2-[(4-fluorobenzyl)amino]ethyl}cyclohexanol I lydrochloride <>6 WO 2005/037207 PCT/US2004/033730 [0287] In an analogous manner to Example 1, step 1 2-(3.4-dichlorophenvl)-A/-(4-f)uorobenzvl)-2-(1-hvdroxycyclohexv))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+KT). [0288] In an analogous manner to Example 1, step 2 1-{1-(3,4-dichlorophenyI)-2-[(4-fluorobenzyl)amino]ethyl}cyclohexanol hydrochloride was prepared from 2-(3,4-dichloropheny!)-A/-(4-fluorobenzyl)-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) rn/z 396/398/400 ([M+H]+); HRMS: calcd for C2iH24CI2FNO HCI, 431.0986; found (ESI), 396.1277. Example 81: 4-[1-(3-bromophenyl)-2-piperazin-1-ylethyi]heptan-4-ol dihydrochloride [0289] In an analogous manner to Example 1, step 1 fe/t-butyl 4-[2-(3-bromophenyl)-3-hvdroxv-3-propylhexanovnpiperazine-1-carboxvlate was prepared from 2-(3-bromophenyl)-3-hydroxy-3-propylhexanoic acid (Reference Example 1-gg) and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 497.2 ([M+H]+). [0290] In an analogous manner to Example 1, step 2 4-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]heptan-4-o! dihydrochloride was prepared from terf-butyl 4-[2-(3-bromophenyl)-3-hydroxy-3-propylhexanoy!]piperazine-1-carboxylate. MS (ES) m/z 383.2 ([M+HH; HRMS: calcd for C19H3iBrN2O ¦ 2.00 HCI, 454.1153; found (ESI), 383.1705. 97 WO 2005/037207 PCT/US2O, 567.2435. [0295] In an analogous manner to Example 1, step 2 1-[1-(3-bromo-4-methoxyphenyl)-2-piperazin-1-y!ethyi]-4-te/f-butylcyclohexano! dihydrochloride was prepared from tert-butyl 4-[(3-bromo-4-methoxyphenyl)(4-terf-butyl-1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 453/455 ([M+H]+); HRMS: calcd for C23H37BrN2O2 " 2.00 HCI, 524.1572; found (ESI), 453.2119. Example 85: 1-[1-(3-ch!orophenyl)-2-piperidin-1-y!ethy!]cyc!ohexanol hydrochloride [0296] In an analogous manner to Example 1, step 1 1 -[1 -(3-chlorophenyl)-2-oxo-2-piperidin-1 -ylethyllcyclohexanol was prepared from (3-ch!orophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-a) and piperidine. HRMS: calcd for C19H26CINO2> 335.1652; found (ESI_FT), 336.17194. [0297] In an analogous manner to Example 1, step 2 1-[1-(3-chloropheny!)-2-piperidin-1-ylethyl]cyclohexanol hydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-oxo-2- 99 WO 2005/037207 PCT/US20U4/033730 piperidin-1-ylethy[]cyclohexanol. HRMS: calcd for Ci9H28CINO • HCI, 357.1626; found '(ES)JFT), 322.19304. Example 86: 2-(3-chIorophenyl)-1,1 -dicyclopropyl-3-(4-methy!pipera2in-1 -yl)propan-1 -ol dihydrochloride [0298] In an analogous manner to Example 1, step 1 ferf-butyl 4-f2-(3-chlorophenyl) (3.3-d)Cvclopropyl-3-hvdroxvpropyl)acetvnpiperazine-1-carboxvlate was prepared from 2-(3-chlorophenyl)-3,3-dicyclopropyl-3-hydroxypropanoicacid (Reference Example 1-hh) and A/-methylpiperazine. MS (ESI) m/z363 ([M+H]+). [0299] In an analogous manner to Example 1, step 2 2-(3-chlorophenyl)-1,1-dicyc!opropyl-3-(4-methylpiperazin-1-yl)propan-1-ol dihydrochloride was prepared from tert-butyl 4-[2-(3-chlorophenyl) (3,3-dicyclopropyl-3-hydroxypropyl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z 349.2037 ([M+HJ+); HRMS: calcd for C20H29CIN2O • 2.00 HCI, 420.1502; found (ESI), 349.2037. Example 87: 1 -[1 -(3-bromophenyl)-2-piperaz!n-1 -ylethyl]-3,3,5,5-tetramethylcyclohexano! dihydrochloride [0300] In an analogous manner to Example 1, step 1 fert-butyl 4-f(3-bromophenvl)(1-hydroxv-3.3.5.5-tetramethvlcyclohexvl)acetvl1piperazine-1-carboxvlate was prepared 100 WO 2005/037207 PCT/US2004/033730 from (3-bromophenyl)(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetic acid (Reference Example 1-ii) and tert-butyl 1-piperazinecarboxylate. [0301] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2-piperazin-i-ylethylj-S.S.S.S-tetramethylcyclohexanol dihydrochloride was prepared, from terf-butyl 4-[(3-bromophenyl)(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetyl]piperazine-1-carboxylate. MS (ES> m/z *23.2 ([M+H]+); HRMS: calcd for C22H35BrN2O, 422.1933; found (ESI), 423.2015. EExample 88:1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]-3,3,5,5-tetramethylcyclohexanol dihydrochloride [0302] 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 -ylethylj-3,3,5,5- tetramethylcyclohexanol (see Example 87). MS (ES) m/z 437.3 ([M+H]+); HRMS: calcd for C23H37BrN2O • 2.00 HCI, 508.1623; found (ESI), 437.2162. Example 89: 3-ethyl-1 -(4-methylpiperazin-1 -yl)-2-(1-naphthyl)pentan-3-ol dihydrochloride [0303] 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-naphthyi)-1- 101 WO 2005/037207 PCT/US2004/033730 piperazin-1-ylpentan-3-o! (see Example 53). MS (ESI) m/z 341 ([M+H]+); HRMS: calcd lor C22H32N2O • 2:00 HCI, 412.2048; found (ESI), 341.2583. Example 90:1-(1-(3-bromopheny!)-2-{[4- (1 rifluoromethy!)benzyl]amino}ethyl)cyclohexanol hydrochloride [0304] In an analogous manner to Example 1, step 1 2-(3-bromophenyl)-2-(1-hvdroxvcyclohexvl)-/V-f4-(tnfluoromethYl)benzyl]acetamide was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-trifiuoromethylbenzylamine. MS (ESI) m/z 470/472 ([M+H]+). [0305] In an analogous manner to Example 1, step 2 1-(1-(3-bromophenyl)-2-{[4- (trifluorome'thyl)benzyl]amino}ethy!)cyclohexanol hydrochloride was prepared from 2-(3- bromophenyl)-2-(1-hydroxycyclohexyI)-A/-[4-(trifluoromethyl)benzyl]acetamide. MS (ESI) m/z 456/458 ([M+H]+); HRMS: calcd for C^HssB^NO ¦ HCI, 491.0838; found (ESI), 456.1147. Example 91: 4-ethyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyc!ohexanol dihydrochloride 102 WO 2005/037207 PCT/US2004/033730 [0305] In an analogous manner to Example 1, step 1 te/f-butvl 4-f1-(1-naphthvO- (4-ethvl-1 -hydroxycyclohexyDacetynpiperazine-i -carboxylate was prepared from (4-ethyl-1-hydroxycyclohexyl) -(1-naphthyl) acetic acid (Reference Example 1-jj) and ferf-butyl 1-piperazinecarboxylate. MS (ESI) m/z481 ([M+Hf); [0307] In an analogous manner to Example 1, step 2 4-ethyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from terf-butyl 4-[1-(1-naphthyl)- (4-ethyl-1-hydroxycyclohexyl)acetyl]pipera2ine-1-carboxylate. MS (ESI) m/z 367 ([M+H]+); HRMS: calcdfor CaaH^NaO • 2.00 HCI, 438.2205; found (ESI), 367.2749. Example 92: 1-{2-(4-methyIpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclobutanol dihydrochloride [0308] In an analogous manner to Example 24, 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyc!obutanol dihydrochloride was prepared from 1-{2-piperazin-1-yl~1-[3-(trifluoromethoxy)phenyl]ethyl}cyclobutanol (see Example 46). HRMS: calcd for C^HasFsNaOz ' 2.00 HCI, 430.1402; found (ESI), 359.1965. Example 93: 4-tert-butyl-1-[1-(3-chlorophenyl)-2-piperazin-1-yIethyl]cyclohexanol dihydrochloride 103 WO 2005/037207 PCT/US2OO4/033730 [0309] In an analogous manner to Example 1, step 1 te/f-butvl 4-[f4-terf-butvl-1-hvdroxvcyclohexvl)('3-chlorophenvi)acetvnp!Perazine-1-carboxvlate was prepared from {3-chlorophenyl)(4-tert-butyl-1-hydroxycyclohexyl)acetic acid (Reference Example 1-kk) and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 493.4 ([M+HJ+). [0310] In an analogous manner to Example 1, step 2 4-te/?-butyf-1-[1-(3-chIorophenyl)-2-piperazin-i-y!ethyl]cyclohexanol dihydrochloride was prepared from terf-butyl 4-[(4-terf-butyl-1 -hydroxycyclohexyl)(3-chlorophenyl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z 379 ([M+H]+); HRMS: caicd for 022^501^0, 378.2438; found (ESI), 379.2513. Example 94: 2-(3-chlorophenyl)-3-ethyl-1 -(4-methyIpiperazin-1 -yl)pentan-3-ol dihydrochloride [0311] In an analogous manner to Example 24, 2-(3-chloropheny!)-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 C18H29CIN2O 2.00 HCI, 396.1502; found (ESI), 325.2032. Example 95: 1-[1-(3-bromophenyl)-2-morpho1in-4-y!ethy!jcyclobutanol hydrochloride KM WO 2005/0372(17 PCT/US2004/033730 [0312] In an analogous manner to Example 1, step 1 1 -H -(3-bromopheny!)-2-mo'-pholin-4-vl-2-oxoethvllcvclobutano) was prepared from (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and morphoiine. HRMS: calcd for C16H2oBrN03) 353.0627; found (ESI_FT), 354.06919. [0313] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2- morpholin-4-ylethyl]cyclobutanol hydrochloride was prepared from tert-buty\ 4-[(4-tert- butyl-1 -hydroxycyclohexyl)(3-chlorophenyl)acetyl]piperazine-1 -carboxylate. HRMS: calcd for C^H^BrNOs ' HCI, 375.0601; found (ESLFT), 340.08898. Example 96: 1-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]-4-tert-buty!cyc!ohexanol dihydrochloride [0314] In an analogous manner to Example 1, step 1 fert-butyl 4-[(3-bromophenvl)(4-fe/f-butvl-1-hydroxvcyclohexvl)acetyl]piperazine-1-carboxylate was prepared from (3-bromophenyl)(4-ferf-butyi-1-hydroxycyclohexyl)aceticacid (Reference Example 1-ff) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 537/539 ([M+H]+); HRMS: calcd for CsrH^BrNaCU, 536.2250; found (ESI), 537.2324. [0315] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2- piperazin-1-ylethyl]-4-terf-butylcyclohexanol dihydrochloride was prepared from tert- butyl . 4-[(3-bromophenyl)(4-terf-butyl-1 -hydroxycyclohexy!)acetyl]piperazine-1 - 105 WO 2005/037207 PCT/US2OO4/03373O carboxylate. MS (ESI) m/z423/425 ([M+H]+); HRMS: calcd for C22H35BrN2O • 2.00 HCI, 494.1466; found (ESI), 423.1994. Example 97:4-methyl-1 -[1 -(1 -naphthyl)-2-piperazin-1 -ylethyljcyclohexanol dihydrochloride [0316] In an analogous manner to Example 1, step 1 fe/f-butvl 4-ri-(1-naphthvP- (4-methyl-1 -hydroxvcvclohexvOacetyllpiperazine-i -carboxylate was prepared from (4-methyl-1-hydroxycyclohexyl) -(1-naphthyI) acetic acid (Reference Example 1-11) and terf-butyl 1-piperazinecarboxylate. MS (ESI) m/z 467 ([M+H]+). [0317] In an analogous manner to Example 1, step 2 4-methyl-1-[1-(1-naphthyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride was prepared from ferf-butyl 4-[1-(1-naphthyl)- (4-methyl-1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI)-m/z 353 ([M+H]+); HRMS: calcd for CssH^NaO 2.00 HCI, 424.2048; found (ESI), 353.2599. Example 98: 1 -{1 -(3-bromophenyl)-2-[(4-fluorobenzyi)amino]ethyl}cyclohexanol hydrochloride [0318] In an analogous manner to Example 1, step 1 2-(3-bromophenvO-/V-(4-fluorobenzylV2-(1 -hvdroxycvclohexvDacetamide was prepared from (3-bromophenyl)(1- 106 WO 2005/037207 PCT/US20O4/03373O - hydroxycyclohexyl)acetic acid (Reference Example 1-b) and 4-fIuorobenzylamine. MS (ESI) m/z 420/422 ([M+Hf). [0319] In an analogous manner to Example 1, step 2 1 -{1 -(3-bromophenyl)-2-{(4-fluorobenzyl)amino]ethyl}cyc!ohexanol hydrochioride was prepared from 2-(3-bromophenyl)-/V-(4-fluorobenzyl)-2-(1-hydroxycyclohexyl)acetamide. MS (ESI) m/z 406 ([M+H]+); MS (ESI) m/z 408 ([M-H}"); HRMS: calcd for C2iH25BrFNO HCl, 441.0870; found (ESI), 406.1173. Example 99: 1-[1-(3-bromophenyl)-2-morpholin-4-ylethy!]cyclohexano! hydrochioride [0320] In an analogous manner to Example 1, step 1 1 -f 1 -(3-bromophenvl)-2-morpholin-4-vl-2-oxoethvl1cvclohexanol 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. [0321] In an analogous manner to Example 1, step 2 1-[1-(3-bromophenyl)-2-morpho!in-4-y)ethyi]cyclohexano! hydrochioride was prepared from 1-[1-(3-bromophenyi)-2-morpholin-4-yl-2-oxoethyl]cyclohexanol. HRMS: calcd for Ci8H26BrNO2 HCl, 403.0914; found (ESLFT), 368.12137. Example 100: 4-terf-buty!-i-f2-(4-methylpiperazin-1-yl)-1-(1-naphthyl)ethyl]cyclohexanol dihydrochloride 107 WO 2005/037207 PCT/US2004/033730 [0322] In an analogous manner to Example 24, 4-te/f-butyl-1-[2-(4-methylpiperazin-1-y[)-1-(1-na"phthyl)ethyl]cyclohexanol dihydrochloride was prepared from 4-terf-butyl-i.-[1-(1-naphthyl)-2-piperazin-1-yiethyl]cyclohexanol (see Example 76). MS (ESI) m/z 409 ([M+H]+); HRMS: calcd for C27H40N2O ¦ 2.00 HCl, 480.2674; found (ESi), 409.3207. Example 101: 4-ferf-buty!-1-[1-(3-chlorophenyl)-2-(4-methylpiperazin-1-yl)ethy!]cyc!ohexano! dihydrochloride [0323] In an analogous manner to Example 24, 4-tert-butyl-1-[1-(3-chlorophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyc!ohexanol dihydrochloride was prepared from 4-ferf-butyl-1-[1-(3-chlorophenyl)-2-piperazin-1-yIethyl]cyclohexanol (see Example 93). MS (ESI) m/z 393 ([M+H]+); HRMS: calcd for C23H37CIN2O 2.00 HCl, 464.2128; found (ESI), 393.2673. Example 102: 1 -methyl-4-[2-morpholin-4-yl-1 -(2-naphthyl)ethyl]piperidin-4-ol hydrochloride 108 WO 2005/037207 PCT/US2OO4/03373O [0324] In an analogous manner to Example 1, step 1 1 -methvl-4-f2-morpholin-4-vl-1 -(2-naphthyl)-2-oxoethvnpiperidin-4-ol was prepared from (4-hydroxy-1-methyipiperidin-4-yl)(2-naphthyl)acetic acid (Reference Example 1-x) and morpholine HRMS: calcd for C^HgsNaOs, 368.2100; found (ESI_FT), 369.21652. [0325] In an analogous manner to Example 1, step 2 1-methyl-4-[2-morpholin-4-yl-1-(2-naphthy!)ethy!]piperidin-4-ol hydrochionde was prepared from 1-methyl-4-[2-morpholin-4-yl-1-(2-naphthyl)-2-oxoethyl]piperidin-4-ol. HRMS: calcd for C22H30N2O2 2.dO HCI, 426.1841; found (ESI_FT), 355.23761. Example 103: 4-[1 -(3-bromophenyl)-2-piperazin-1 -ylethyl]tetrahydro-2/-/-pyran-4-o! dihydrochloride [0326] In an analogous manner to Example 1, step 1 terf-butyl 4-f(3-bromophenyl)(4-hvdroxytetrahydro-2H-pyran-4-vl)acetynpiperazine-1-carboxylate was prepared from (3-bromophenyl)(4-hydroxytetrahydro-2H-pyran-4-yl)acetic acid (Reference Example 1-mm) and fe/f-butyl 1-piperazinecarboxylate. MS (ESI) m/z483/485 ([M+H]+); HRMS: calcd forC22H3iBrN2O5) 482.1416; found (ESI), 483.1508. [0327] 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 tert- butyl 4-[(3-bromophenyl)(4-hydroxytetrahydro-2/-/-pyran-4-yl)acetyl]piperazine-1 - carboxylate. MS (ESI) m/z 369/371 ([M+H]+); HRMS: calcd for C17H25BrN2O2 • 2.00 HCI, 440.0633; found (ESI), 369.1166. 109 WO 2005/037207 PCT7US2004/033730 Example 104: 1 -{1 -[3-(benzyloxy)phenyl]-2-piperazin-1 -ylethyi}cyclohexanol dihydr<5ch!oride [0328] In an analogous manner to Example 1, step 1 fe/t-butv! 4-IT3-Cbenzvloxv)phenvnn-hvdroxvcvclohexvnacetvnpiperazine-1-carboxylate was prepared from (3-benzyloxyphenyl)(4-hydroxycyclohexyl)acetic acid (Reference Example 1-nn) and terf-buty! 1 -piperazinecarboxylate. MS (ESI) m/z 509 ([M+H]+); HRMS: calcdfor C30H40N2O5, 508.2937; found (ESI), 509.2997. [0329] In an analogous manner to Example 1, step 2 1-{1-[3-(benzy!oxy)phenyl]-2-piperazin-1-ylethy!}cyclohexanol dihydrochloride was prepared from ferf-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 no WO 2005/037207 PCT/US2canoI hydrochloride was. prepared from 1-[1-(3,4- dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]cyclohexanol. HRMS: calcd for Ci8H25CI2NO2 HCI, 393.1029; found (ESI_FT), 358.13358. Example 113: 1-[2-[(4-fluorobenzyl)amino]-1-(2-naphthyl)ethyl]cyclohexanol hydrochloride [0345] In an analogous manner to Example 1, step 1 A/-(4-fluorobenzvP-2-(1 -hydroxvcvclohexvn-2-(2-naphthy()acetamide was prepared from (1-hydroxycyclobutyl)(2-naphthyl)acetic acid (Reference Example 1-c) and 4-fluorolbenzylamine. MS (ESI) m/z372 ([M+H-H2O]+). [0346] 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. , 135 WO 2005/037207 ' PCT/US2OO4/033730 Example 114:4-f1-(3,4-dich!orophenyl)-2-morpholin-4-ylethyI]-1-methylp!peridin-4-ol dihydrochloride [0347] In an analogous manner to Example 1, step 1 4-H-(3.4-dichlorophenyl)-2-morpholin-4-vl-2-oxoethvn-1-methylpiperidin-4-ol was prepared from (3,4-dichlorophenyl){4-hydroxy-1-methylpiperidin-4-yl)acetic acid (Reference Example 1-i) and morpholine. HRMS: calcd for C18H24Cl2N2O3, 386.1164; found (ESl_FT), 387.12304. [0348] In an analogous manner to Example 1, step 2 4-[1-(3,4-dichlorophenyl)-2-morpho!in-4-ylethyl]-1-methy!piperidin-4-ol dihydrochioride was prepared from 4-[1-(3,4-dichlorophenyl)-2-morpholin-4-yl-2-oxoethyl]-1-methyipiperidin-4-oI. HRMS: calcd for Ci8H26Cl2N2O2 ¦ 2.00 HCI, 444.0905; found (ESLFT), 373.14421. Example 115:1-[1-[3-(benzyloxy)phenyl]-2-(4-methylpiperazin-1-yl)ethyl]cyclobutanol dihydrochioride [0349] In an analogous manner to Example 24, 1-[1-[3-(benzyloxy)phenyI]-2~(4-methylpiperazin-1-yl)ethyl]cyclobutanol dihydrochioride 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. 116 WO 2(105/037207 PCT/US2004/033730 Example 116:4-[1-(3-bromophenyl)-2-morpholin-4-ylethyl]-1-methylpiperidin-4-ol dihydrg^Viloride [0350] In an analogous manner to Example 1, step 1 4-f 1 -C3-bromophenvl)-2-morpholin-4-vl-2-oxoethyl]-1-methylpiperidin-4'Ol was prepared from (3-bromophenyl)(4-hydroxy-1-methylpiperidin-4-yl)aceticacid (Reference Example 1-r) and morpholine. HRMS: calcd for C18H25BrN2O3, 396.1049; found (ESLFT), 397.11148. [0351] In an analogous manner to Example 1, step 2 4-[1 -(3-bromophenyl)-2-morphoiin-4-ylethyl]-1-rnethylpiperidin-4-ol dihydrochloride was prepared from 4-[1-(3-bromophenyl)-2-morpholin-4-yl-2-oxoethyl]-1-methylpiperidin-4-ol. HRMS: calcd for C18H27BrN2O2 • HCI, 418.1023; found (ESI_FT), 383.13261. Example 117: 1 -(1 -(3-chlorophenyl)-2-f44(6-methoxy-2-naphthyl)methynpiperazin-1 - vllethvDcyclohexariol dihydrochloride [0352] A solution of 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) (200 mg, 0.62 mmol) and S-methoxy-2-napthaldehyde (173 mg, 0.93 mmol) in dichloroethane (4 mL) was treated with sodium trisacetoxyborohydnde (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- 117 WO 2005/037207 PCT/US2004/033730 ch[orophenvl)-2-(4-[(6-methoxv-2-naDhthvl)methvnpiperazin-1-vHethvl)cvclohexanol dihvdrochlonde as a white solid. MS (ESI) m/z493/495 ([M+H]+); HRMS: calcd for C3oH37CIN202 • 2.00 HCI, 564.2077; found (ESI_FT), 493.2632. Example 118: 1-(1-(3-chlorophenvn-244-(cyclopropvlmethvl)piperazin-1-yliethvDcyclohexanol dihydrochloride [0353] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyi)-2-f4-(cvclopropvlmethyl)piperazin-1-vnethyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]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: 141-(3-chlorophenvO-244-(cvclohex-3-en-1-ylmethyl)piperazin-1- yljethyl)cyclohexanof dihydrochloride [0354] In an analogous manner to Example 117, 1 -d -(3-chlorophenvl)-244-(cyclohex-3-en-1 -ylmethyl)pipera2in-1 -yliethyflcyclohexanol 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. 118 WO 2005/037207 PCT/US2004/033730 Example 120: 6-(f4-r2-(3-chlorophenv0-2-n -h.vdroxycyclohexvOethynpiperazin-1-yl)methyl)tetrahydro-2/-£pyran-2-ol dihydrochloride [0355] In an analogous manner to Example 117, 6-((4-[2-(3-chlorophenyl)-2-(1 -hydroxvcvclohexyl)ethvnpiperazin-1-vl}methvl)tetrahydro-2H-pyran:2-ol dihydrochloride was prepared from 1-[1-(3-ch!orophenyi)-2-piperaztn-1-ylethyl]cyc!ohexanol (see Example 1) and 3,4-dihydro-2H-pyran-2-carDoxaldehyde. HRMS: calcdfor C24H37CIN2O3 • 2.00 HCI, 508.2026; found (ESI), 419.2455. Example 121: 1 -(1 -(3-chlorophenvl)-2-r4-(3-phenvlbutyi)piperazJn-1 -yl]ethyl}cyclohexanol dihydrochioride [0356] In an analogous manner to Example 117, 1 -fi -(3-chlorophenyl)-2-[4-(3-phenvlbutyl)piperazin-1 -yllethyDcyclohexanol dihydrochloride was prepared from 1-[1-(3-ch!orophenyi)-2-piperazin-1-y!ethyl]cyc!ohexanol (see Example 1) and3-phenylbutyraldehyde. MS (ESI) m/z 455/457 ([M+H]+); HRMS: calcd for C28H39CIN2O ¦ 2.00 HCI, 526.2284;,found (ESLFT), 455.28235. Example 122: 1-f1-(3-chloropheny|)-2-f4-(2-phenvlethvl)piperazin-1-vnethvllcyclohexanoj di hydrochloride 119 WO 2005/037207 PCT/US2004/033730 [0357] In an analogous manner to Example 11/, 1 —f 1 -(3-chlorophenyl)-2-f4-(2-phenvlethvl)p1perazin-1 -vnethvDcyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and phenylacetaldehyde. MS (ESI) m/z427/429 ([M+Hf); HRMS: calcd for C26H35CIN2O 2.00 HCI, 498.1971; found (ESI), 427.2505. Example 123: 1-f1-(3-chlorophenvl)-2-f4-(3-phenoxvbenzvQpiperazin-1-yl]ethyl)cyclohexanof dihyd rochloride [0358] In an analogous manner to Example 117, 1 -«f 1 -(3-chlorophenyl)-2-r4-(3-phenoxvbenzyl)piperazin-1-ynethyl)cyclohexanoldihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-y!ethyl]cyclohexanol (see Example 1) and 3-phenoxybenzaldehyde. MS (ESI) m/z505/507 ([M+H]+); HRMS: calcd for C^HziOHzOz 2.00 HCI, 576.2077; found (ESI_FT), 505.26266. 120 Example 124: 1-{1-(3-chlorophenvn-2-[4-(2-naphthvlmethyQpiperazin-1-yliethyDcyclohexanol dihydrochloride WO 2005/037207 PCT/US2004/033730 [0359] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-r.4-(2-naphthylmethyl)piperazin-1-ynethyl)cyclohexanol dihydrochloride was prepared from 1 -[1-(3-cWstropheny!)-2-piperazin-1-ylethyl3cyciohexano! (see Example 1) and 2-napthaldehyde. MS (ESI) m/z463/465 ([M+H]"); HRMS: calcd for C2gH35C!N2O • 2.00 HCI, 534.1971; found (ESI), 463.2499. Example 125: 1 -(1 -(3-chlorophenvfl-2-f4-(3-f urylmethvPpiperazin-1 -vnethyl}cvclohexanoldihydrochloride [0360] In an analogous manner to Example 117, 1 -f1-(3-chiorophenvl)-2-[4-f3-furylmethyl)piperazin-1 -yrjethyllcyclohexanol dihydrochloride was prepared from 1 -[1 -(3-chlorophenyl)-2-piperazin-1-ylethyl]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-f3-chlorophenyl)-2-l4-fcyclohexylmethyl)piperazin-1-vnethvl}cyclohexanol dihydrochloride [0361 ] In an analogous manner to Example 117, 1 -f1-(3.-chlorophenyl)-2-f4-(cvclohexylmethyl)piperazin-1-vnethyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-yIethyl]cyclohexanol (see Example 1) and cyclohexanecarboxaldehyde. MS (ESI) m/z419/421 ([M+H]+); HRMS: calcd for C25H39CIN2O • 2.00 HCI, 490.2284; found (ESI), 419.2815. 121 WO 2005/037207 PCT/US2004/033730 Example 127: 1 -(1 -(3-chlorophenvl)-2-f4-(quinolin-4-vlm ethyl)piperazin-1 -ynethyllcyclohexanol dihydrochloride [0362] In an analogous manner to Example 117, 1-(1-(3-chlorophenyQ-2-f4-(o;uinoiin-4-ylmethyl)piperazin-1 -vl1ethyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 1) and 4-qumolinecarboxaldehyde. MS (ESi) m/z 464/466 ([M+H]+); HRMS: calcd for C28H34CIN3O " 3.00 HCI, 571.1691; found (ES!_FT), 464.24693. Example 128: 1 -d -(3-chlorophenvl)-2-(4-f(5-ethyl-2-f urvDmethylipiperazin-i -vUethyQcyclohexano) dihydrochloride [0363J In an analogous manner to Example 117,1 -(1 -(3-chlorophenyl)-2-(4-f(5-ethyl-2-furyl)methvnpiperazin-1-vl)ethyl)cyclohexanol dihydrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyi]cyc!ohexanol (see Example 1) and 5-ethy!-2-furaldehyde. MS (ESI) m/z[M+H]+ (431/433); HRMS: calcd for C25H35CIN2O2 2.00 HCI, 502.1921; found (ESI), 431.2454. Example 129: 1-(1-(3-chlorophenvD-2-f4-(2-phenylpropvDpiperazin-1-ynethyl}cyclohexanol dihydrochloride 122 WO 2005/037207 PCT/US2004/033730 [0364] In an analogous manner to Example 117,1 -f 1 -(3-chlorophenvQ-2-r4-(2-phenvlpropvl)pipera2in-1-vnethyl}cvclohexanol dihvdrochloride 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 -f2-[4-(1 -benzofuran-2-vlmethvflptperazin-1 -yil-1 -(3-chlorophenvOethvncvclohexanol dihvdrochloride [036,5] In an analogous manner to Example 117, 1 -f2-[4-(1 -Jbenzofuran-2-ylmefhyl)piperazin-1 -yll-1 -(3-ehlorophenvl)ethvncvclonexanol djhydrochloride was prepared from 1-[1-(3-chlorophenyI)-2-pipera2in-1-ylethyl]cyclohexanol (see Example 1) and benzo[B]furan-2-carboxaldehyde. MS (ESI) m/z [M+H]+ (453/455); HRMS: calcd for C27H33CIN2O2 ' 2.00 HCI, 524.1764; found (ESI), 453.2296. 123 Example 131: H2-(4-[4-(benzvloxv)benzvnpiperazin-1-yl}-1-(3-chlorojphenvnethylicvclohexanol dihvdrochloride WO 2005/037207 PCT/US2004/03373U [0366] In an analogous manner to Example 117,1 -f 2-(4-f 4- fbenzyjj>xv)benzyPpiperazin-1 -vl)-1 -(3-chforophenvDethvHcvclohexanol dihvdrochloride was prepared from 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethy(]cyclohexanol (see Example 1) and 4-benzyloxybenza!dehyde. MS (ES!) m/z519/521 ([M+H]+); HRMS: calcd for C32Ho9CIN202 2.00 HCI, 590.2234; found (ESI_FT), 519.27544. Example 132: 1-(1-(3-chlorophenvO-2-l4-(4-phenoxvbenzyl)pipera2in-1-yl]ethvl)cyclohexanol dihvdrochloride [0367] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenyl)-2-r.4-(4-phenoxybenzyl)piperazin-1-vnethvncvclohexanol dihvdrochloride was prepared from 1 -[1-(3-chlorophenyl)-2-piperazin-1-y)ethyl]cyclohexanol (see Example 1) and 4-phenoxybenzaldehyde. MS (ESI) m/z505/507 ([M+H]+); HRMS: calcd for C3iH37CIN2O2 • 2.00 HCI, 576.2077; found (ES)_FT), 505.26224. Example 133: 1-(1-(3-chlorophenvn-2-r4-Cpvridin-4-vlmethyl)piperazin-1-yllethvljcvclohexanol dihvdrochloride [0368] In an analogous manner to Example 117, 1 -(1 -(3-chlorophenvl)-2-r4-(pvridin-4-ylmethvQpiperazin-1 -vliethyljcyclohexanol dihydrochloride was prepared from 1 -[1 -(3-ch!orophenyl)-2-piperazin-1-y!ethy(]cyclohexanol (see Example 1) and 4-pyridinecarboxaldehyde. MS (ESI) m/z [M+HJ+ (414/416); HRMS: calcd for C24H32CIN3O 2.00 HCI, 485.1767; found (ESI), 414.2307. 124 WO 2005/037207 PCT/US2004/UJJ7J0 Example 134 : 1-(1-(3-chlorophenvlV244-(pvn\Jin-3-vlmethvQpiperazin-1-yl]ethvl>cyclohexanol dihvdrochioride [0369] In an analogous manner to Example 117, 1-{1-(3-ch)orophenyl)-2-[4-(pyridin-3-ylmethy{)piperazin-1-yl]ethyJ}cyclohexanol dihydrochloride was prepared from 1-[1-(3-ch!orophenyi)-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: H1-(3',4'-dichloro-1.1'-biphenvI-3-vl)-2-piperazin-1-vlethvncvcfohexanol dihvdrochioride [0370] Step 1: In an analogous manner to Example 1, step 1 te/f-butyl 4-F(3-bromophenvl)(1-hvdroxvcvclohexvl)acetvlipiperazine-1-carboxvlate was prepared from (3-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-b) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C23H33BrN2O4, 480.1624; found (ESL.FT), 481.16857. [0371] Step 2: A solution of tert-butyl 4-[(3-bromophenyl)(1- hydroxycyclohexyl)acetyl]piperazine-1-carboxylate (2.12 g, 4.40 mmol) in dry 125 WO 2005/037207 PCT/US20U4AI33730 tetrahydrofuran (10 ml_) under nitrogen was treated dropwise with a solution of borane (1.0 M intetrahydrofuran, 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%) ferf-butvl 4-f2-(3-bromophenvn-2-(1-hvdroxvcyclohexvl)ethvlipiperazine-1-carboxylate as a white powder. MS (ESI) m/z 467/469 ([M+HJ+); HRMS: calcd for CasHgsBrNaOs, 466.1831; found (ESI), 467.1899; Anal. Calcd for C23H35BrN2O3: C, 59.10; H, 7.55; N, 5.99-. Found: C, 59.14; H, 7.72; N, 5.77. [0372] Step 3: A mixture of tert-buty! 4-[2-(3-bromophenyl)-2-(1- hydroxycyclohexy!)ethyl]piperazine-1-carboxylate (0.72 g, 1.55 mmol) and tetrakis(triphenylphosphine)palladium (37 mg, 0.032 mmol, 10 mol%) in 1,2-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-butyl 4-r2-(3',4'-dichloro-biphenvt-3-yl)-2-(1 -hvdroxycvclohexvOethylipiperazine-1 -carboxylate as a foam, which was used as such in the next step. [0373] Step 4: tert-butyl 4-[2-(3',4'-dichloro-biphenyl-3-yl)-2-(1- hydroxycyclohexyl)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 126 WO 2005/037207 PCT/US2004/03373O 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-f1-(3'.4'-dichloro-1,1'-biphenvl-3-vl)-2-piperazin-1-vlethvllcyclohexanol dihvdrochloride as a white solid. MS (ESI) m/z 433/435/437 ([M+H]+); HRMS: calcd for C24H30N2OCU • 2.00 HCI, 433.1813; found (ESI), 433.1813 Example 136:1-f1-(1,1'-biphenvl-3-vl)-2-piperazin-1-vlethvncyc1ohexanol dihydrochloride . [0374] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(1,1'-biphenyl-3- vlV2-(1 -hydroxvcyclohexyDethvlipiperazine-i -carboxylate was prepared from tert-buty! 4-[2-(3-bromophenyl)-2-(1 -hydroxycyciohexyl)ethyljpiperazine-1 -carboxylate (see Example 135, step 2) and phenyl boronic acid. [0375] In an analogous manner to Example 135, step 4 1 -f 1 -(1,1 '-biphenvl-3-vl)-2-piperazin-1-ylethvncyclohexanol dihvdrochloride was prepared from tert-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-vlethvl]cvclohexanol 127 dihvdrochloride WO 2005/037207 PCT/US2(KI4/()33730 [0376] In an analogous manner to Example 135. step 3 tert-butvl 4-f2-(4'-chloro-biphenyl-S-vn^-CI-hvdroxvcyclohexvDethvHpiperazine-i-carboxvlate was prepared from tert-buty! 4-[2-(3-bromophenyl)-2-(1-hydroxycycIohexyl)ethyl]pipera2ine-1-carboxylate (see Example 135, step 2) and 4-chloropheny! boronic acid. [0377] In an analogous manner to Example 135: step 4 1 -f 1 -(4'-chloro-i. 1 '-bfphenyl-3-yl)-2-piperazin-1-vlethvncyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(4'-chloro-biphenyi-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 399/401 ([M+H]*); HRMS: calcd for C24H31CIN2O • 2.00 HCI, 470.1658; found (ESI), 399.2203. Example 138:1 -[1 -(3'-methoxy-1,1 '-biphenyl-3-y!)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0378] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'-methoxv-biphenyl-3-yl)-2-(1-hydroxvcyclohexyl)ethvl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1 -hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (see Example 135, step 2) and 3-methoxyphenyl boronic acid. [0379] In an analogous manner to Example 135, step 4 1 -f1 -(3'-methoxy-1.1 '-biphenvl-3-yQ-2-piperazin-1 -vlethvlicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3'-methoxy-biphenyl-3-yl)-2-(1 -hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 395 ([M+H]+); HRMS: calcd for C25H34N2O2 2.00 HCI, 466.2154; found (ESI), 395.269. Example 139: 1 -[1 -(3'-chloro-1,1 '-biphenvl-3-yl)-2-piperazin-1 -ylethyllcyclohexanol dihydrochloride 128 WO 2005/037207 PCT/US2004/033730 [0380] In an analogous manner to Example 135, step 3 tert-butyi 4-r2-(3'-chioro-biDhenvl-3-vl)-2-(1-hvdroxvcvclohexvnethvliDiperazine-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. [0381] In an analogous manner to Example 135, step 4 H1-(3'-chloro-1,1'-biphenyl-3-vD-2-piperazin-1 -ylethyllcyclohexanol dihvdrochloride was prepared from tert-butyl 4-[2-(3'-chloro-biphenyl-3-yl)-2-(1 -hydroxycyclohexy!)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 399/401 ([M+H]+); HRMS: calcd for C24H3iCIN2O 2.00 HCI, 470.1658; found (ESI), 399.2183. Example 140: 1 -[1 -(2'-fluoro-1,1 '-biphenyl-3-yl)-2-piperazin-1 -ylethyl]cyclohexano! maleate [0382] In an analogous manner to Example 135, step 3 tert-butyl 4-f2-(2'-fluoro-biphenvl-3-yl)-2-(1-hvdroxycvclohexvl)ethvnDiperaz?ne-1-carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclobexyl)ethyl]piperazine-1 -carboxylate (see Example 135, step 2) and 2-florophenyl boronic acid. [0383] In an analogous manner to Example 135, step 4 1-M-(2'-fluoro-1.1'-biphenyl-3-yl)-2-piperazin-1-ylethvncyclohexanol dihvdrochloride was prepared from tert-butyl 4-[2-(2'-fluoro-biphenyl-3-yI)-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: 129 WO 2(105/037207 PCT/US2WI4/033730 1,1 '-biphenvl-3-vl)-2-piperazin-1 -vlethvHcvc(ohexanol maleate as a colorless solid. MS (ESI) m/z 383 ([M+H]+); Anal. Calcd for C24H3iFN2O . 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-f1-(2,5-dichlorothien-3-vlV2-piperazine-1-vlethvl]cvclohexanol djhyd rpchlori.de [0384] 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 (3.1 g , 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-dich!orothien-3-v0acetic acid as a brown solid, which was used as such in the next step. MS (ESI) m/z 209/211/213 ([M-H]-). [0385] Step 2: in an analogous manner to Example 1, step 1 tert-butyl 4-f.f2.5-dichlorothien-3-yl)acetvHpiperazine-1-carboxvlate was prepared from 2,5-dichlorothiophene-3-acetic acid and tert-butyl 1-piperazinecarboxy!ate. The product was crystallized from ethyf acetate: hexane to yield a colorless solid. [0386] Step 3: A solution of diisopropyl amine (0.80 mL, 5.6 mmol) in dry tetrahydrofuran (10rnL) 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-yi)acetyl]piperazine-1- 130 WO 2005/037207 PCT/US2004/033730 carboxyiate (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-f(2,5-dichlorothien-3-yl)(1 -hvdroxycvclohexvl)acetvnpiperazine-1-carboxylate as a white foam. MS (ESI) m/z 477/479/481 ([M+H]), HRMS: calcd for C21 H3oCI2N204S, 476.1303; found (ESI), 477.1362. [0387] Step 4: In an analogous manner to Example 135, Step 2 tert-butyl 4-f2-f2.5-dichlorothien-3-yl)-2-( 1 -hydroxvcyclohexvPethvlipiperazine-i -carboxylate was prepared from tert-butyl 4-[(2,5-dich!orothien-3-yl)(1 -hydroxycyclohexyl)acety!]piperazine-1 -carboxylate. MS (ESI) m/z 463/465/467 ([M+H]+), HRMS: calcd for C^HssClsNaOsS, 462.1511; found (ESI), 463.1594. [0388] Step 5: In an analogous manner to Example 135, step 4 1-f1-(2.5-dichlorothien-3-yl)-2-piperazine-1 -ylethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(2.5-dichlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethy!]piperazine-1-carboxylate and isolated as a colorless powder. MS (ESI) m/z [M+H]+ (363/365/367); HRMS: calcd for C16H24C!2N2OS • 2.00 HCl, 434.0520; found (ESI), 363.1035. Example 142:1 -["1 -f5-chlorothien-2-yl)-2-piperazin-1 -ylethvllcyclohexanol 131 djhydrochloride WO 2005/037207 PCT/US2U04/033730 [0389] In an analogous manner to Example 141, step 1 (5-chlorothien-3-vl)acetic acid wasprepared from 2-thiophene acetic acid and N-chlorosuccinimide. (This acid was used-iCReference Example 1-rr) MS (ES) m/z 175.0 ([M-H]-) [0390] In an analogous manner to Example 1, step 1 tert-butyl 4-r(5-chtorothien-2-vOH -hvdroxvcvclohexvl)acetyflpiperazine-1 -carboxvlate was prepared from (5-chlorothien-2-yl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-rr) andJ tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 443/445 ([M+H]+) [0391] In an analoguous manner to Example 1, step 2 1 -M -(5-chlorothien-2-vO-2-piperazjn-1 -ylethyncvclohexanol dihydrochloride product was prepared from tert-butyl 4-[(5-chlorothien-2-yl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxy!ate. 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 -f 1 -(5-bromothien-2-yl)-2-piperazin-1 -vlethvlicyclohexanol dihydrochloride [0392] 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) [0393] In an analogous manner to Example 1, step 1, tert-butyl 4-[(5-bromothien-2-yl) (1 -h yd roxycyclohexyl) acetyll pipe razi ne-1 -carboxvlate was prepared from (5-bromothien-2-yl)(1-hydroxycyclohexy!)acetic acid (Reference Example 1-ss) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 487/489 ([M+H]+ 132 WO 2005/037207 PCT/US2004/03373O [0394] In an analogous manner to Example 1, step 2, 1 -M -(5-bromothien-2-vl)-2-piperazin-1 -vlethvltcyclohexanol dihydrochloride was prepared from tert-butyl 4-[(5-bromotn~ien-2-yl)(1-hydroxycyc!ohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 373/375 ([M+H]+)- Anal. Calcd for Ci6H25BrN2OS ¦ 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 -f 1 -(5-chlorothien-3-vl)-2-piperazin-1 -vlethvllcyclohexanol dihydrochloride [0395] In an analogous manner to Example 1, step 1 tert-butyl 4-f(5-chlorothien-3-vDacetyllpiperazine-i-carboxylate was prepared from 5-ch!orothiophene-3-acetic acid2 and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 289.0 ([M+H-C4H8]+); HRMS: calcd forC15H21CIN2O3S, 344.0961; found (ESI), 345.1018 [0396] In an analogous manner to Example 141, step 3, tert-butyl 4-f2-(5-chlorothien-3-yl)-2-(1 -hydroxvcvclohexvl)ethvnpiperazine-1 -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 C21H33CIN2O3Sf 428.1900; found (ESI), 429.1973. [0397] In an analogous manner to Example 135, step 2, tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxvcyclohexyl)ethyl)piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. [0398] In an analogous manner to Example 135, step 4 1 -[1 -(5-chlorothien-3-yl)-2-piperazin-1-ylethvlicyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(5-chlorothien-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate. MS (ES) m/z ' Monguzzi, R , Libassi, G.; Pinza, M.; Piffen, G. Synthesis of new a-hydrazmoarylacebc acids and derivatives Farmaco, Edizione Scientifica (1976), 31(8), 549-60 1J3 WO 2005/037207 ' PCT/US2O04/03373O 329/331 ([M+H]+); HRMS: calcd for C16H25CIN2OS • 2.00 HCI, 400.0910; found (ESI), 329.1444. Example 145:1 -[2-(4-aminopiperidin-1 -yl)-1 -(5-chIorothien-3-yl)ethyl]cyclohexanol dihydrochloride [0399] In an analogous manner to Example 1, step 1 tert-butyl(1-r2-(5-chloro-thiophen-3-yl)-acetvn-piperidin-4-vl}-carbamate was prepared from 5-chlorothiophene-3-acetic acid and 4-N-boc-aminopiperidine. [0400] In an analogous manner to Example 141, step 3, tert-butylf 1 -f2-(5-chloro- thiophen-3-vl)(1-hydroxvcvclohexyl)acetvn-piperidin-4-yl)-carbamate was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)-acetyl]-piperidin-4-yl}-carbamate and cyclohexanone. [0401] In an analogous manner to Example 135, step 2, tert-buty!{1 -f2-(5-chloro-thiophen-3-yl)(1-hvdroxvcvcloriexvl)ethvl|-piperidin-4-vl)-carbamate was prepared from tert-butyI{1-[2-(5-Chloro-thiophen-3-yl).(1-hydroxycyclohexyl)acetyl]-piperidin-4-yl}-carbamate.) [0402] In an analogous manner to Example 135, step 4 1 -f2-(4-aminopiperidin-1 -vl)-1 -(5-chlorothien-3-yl)ethvncyclohexanol dihydrochloride was prepared from tert-butyl{1-[2-(5-Chloro-thiophen-3-yl)(1 -hydroxycyclohexyi)ethyl]-piperidin-4-yl}-carbamate. MS (ES!) 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-yi)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochioride 134 WO 2005/037207 PCT/US2004/033730 [0403] In an analogous manner to Example 1, step 1 t-butyl 4-[1-r,1-(1-benzothien-3-yl)(1 -hydroxycyclohexyDacetyllpiperazine-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]+ [0404] In an analoguous manner to Example 1, step 2 1 -[1 -(1 -benzothien-3-yl)-2-piperazin-1 -ylethvncyclohexanol 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 C2oH28N2OS ¦ 2.00 HCI, 416.1456; found (ESI), 345.2024 Example 147: 1-f1-(3',4'-difluoro-1.1'-biphenyl-3-vl)-2-piperazin-1-vlethvncyclohexanol dihydrochloride [0405] In an analogous manner to 'Example 135, step 3 tert-butvl 4-[2-(3'.4'-difluoro-biphenyl-3-vl)-2-(1-hvdroxvcyclohexyl)ethyllpiperazine-1-carboxylate was prepared from tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (see Example 135, step 2) and 3,4-difluorophenyl boronic acid. [0406] In an analogous manner to Example 135, step 4 1-n-(3',4'-difiuoro-1.1'-biphenyl-3-yl)-2-piperazin-1-vlethyl]cyclohexanol dihydrochloride was prepared from tert-butyl 4-[2-(3',4'-dif luoro-biphenyl-3-yl)-2-(1 -hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z [M+H]+ (401); HRMS: calcd for C24H30F2N2O 2.00 HCI, 472.1860; found (ESI), 401.2378 135 WO 2005/037207 PCT/US2004/033730 Example 148:1 -f 1 -(3'.4'-dichloro-1,1 '-biphenvl-2-y[)-2-piperazin-1 -vlethyl]cyclohexanol dihydrochloride [0407] In an analogous manner to Example 1, step 1 tert-butvl 4-lY2-bromophenvl)(1-hvdroxvcvclohexyl)acetvnpiperazine-1-carboxvlate was prepared from (2-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-uu) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 481/483 ([M+H]+); HRMS: calcd for C23H33BrN2O4, 480.1624; found (ESI), 481.1689 [0408] In an analoguous manner to Example 135, step 2, tert-butvl 4-[2-(2- bromophenvl)-2-(1-hydroxvcyclohexyl)ethyHpiperazine-1-carboxvlate was prepared from tert-butyl 4-[(2-bromophenyl)(1-hydroxycyclohexyI)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 467/469 ([M+HJ+); HRMS: calcd for CasHssBrNaOs, 466.1831; found (ESI), 467.1895; [0409] In an analogous manner to Example 135, step 3 tert-butvl 4-r3'4'dichloro-1,1 '-biphenyl-2-vl)-2-(1-hvdroxycvclohexvnethvnpiperazine-1-carboxylate was prepared from tert-butyl 4-[2-(2-bromophenyl)-2-(1-hydroxycycIohexyl)ethyl]piperazine-1-carboxylate and 3,4-dichloro phenyl boronic acid. [0410] In an analogous manner to Example 135, step 4 1-f1-(3'.4'-dichloro-1,1'-biphenyl-2-vl)-2-piperazin-1-vlethvl]cvclohexanol 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 C24H30CI2N2O 2.00 HCI, 504.1269; found (ESI), 433.1797 ' 136 WO 2005/037207 PCT/US2004/0337JO Example 149: 1-[1-(1.1'-biphenvl-2-vl)-2-piperazin-1-vlethyllcyclohexanol dihydrochlork" [0411] In an analogous manner to Example 135, step 3 tert-butyl 4-[1,1 '-biphenyl-2-yl)-2-(1-hvdroxvcvclohexyl)ethyl]piperazine-1-carboxvlate was prepared from tert-butyl 4-[2-(2-bromophenyI)-2-(1 -hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate (see Example 148, step 2) and phenyl boronic acid. [0412] 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'-bipheny(-2-yl)-2-(1-hydroxycyclohexyI)ethyl]piperazine-1-carboxylate. MS (ES) m/z 365 4 ([M+H]+); HRMS: calcd for C24H32N2O • 2.00 HCI, 436.2048; found (ESI), 365.2601 Example 150:1-[1-(3'-ch!oro-1,1'-biphenyl-2-yl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride [0413] In an analogous manner to Example 135, step 3 tert-butyl 4-[3'-chloro-1,1'-biphenyl-2-yl)-2-(1-hydroxvcyclohexyl)ethyl]piperazine-1 -carboxylate was prepared from tert-butyl 4-[2-(2-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 148, step 2) and 3-chloro phenyl boronic acid. 137 WO 2005/037207 PCT/US2004/033730 [0414] In an analogous manner to Example 135, step 4 1 -[1 -(3'-chloro-1.1 '-biphenyl-2-yl)-2-piperazin-1 -ylethylicvclohexanol dihydrochloride was prepared from tert-butyl 4-[3'-chloro 1r1 '-biphenyl-2-yl)-2-(1 -hydrpxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 561/563/565 ([M+H]+); HRMS: calcd for C24H31CIN2O 2.00 HCI, 470.1658; found (ESI), 399.2211 Example 151: 1-{1-[2-(1,3-benzodioxo!-5-yl)phenyl]-2-piperazin-1-ylethy)}cyclohexanol dihydrochloride [0415] In an analogous manner to Example 135, step 3 tert-butyl 4-[1-(1,3-benzodioxol-5-ylphenvl)2-(1-hvdroxvcvclohexyl)ethynpiperazine-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. [0416] In an analogous manner to Example 135, step 4 1 -{1 -[2-(1.3-benzodioxol-5- yl)phenvn-2-piperazin-1-ylethvl)cyclohexanol dihydrochloride was prepared from tert- butyl 4-[1 -(1,3-benzodioxol-5-ylphenyl)-2-(1 -hydroxycyciohexyl)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 -r2-(4-aminopiperidin-1 -yl)-1 -Q'^'-dichloro-i. 1 '-biphenyl-3-yl)ethvncyclonexanol dihydrochloride 138 WO 2005/037207 PCT/US2004/033730 [0417] In an analogous manner to Example 135, step 3 tert-butvl {1-[(3'.4'-dichloro-1.1 '-biphenyl-3-vl)(1 -hvdroxvcvclohexyl)cetvnp'iperidin-4-vl)carbamate was prepared from_tert-butyl {1 -[(3-bromopheny!)(1 -hydroxycyciohexyl)acetyI]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 [0418] In an analogous manner to Example 135, step 2 tert-butvl {1-[2-(3'.4'-dichloro-1,1 '-biphenyl-3-yl)-2-(1 -hydroxvcvclohexyl)ethvnpiperidin-4-yl)carbamate was prepared from tert-butyl {1-[(3',4'-dichloro-1,1'-biphenyl-3-yl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate. MS (ES) m/z 547.3 ([M+H]+); HRMS: calcd for C30H40Cl2N2O3, 546.2416; found (ESI), 547.2473. [0419] In an analogous manner to Example 135, step 3 1 -[2-(4-aminopiperidin-1 -yl)-1 -(3',4'-dichloro-1.1 '-biphenvl-3-yl)ethvlicyclohexanol dihydrochloride was prepared from tert-butyl {1-[2-(3',4'-dichloro-1,1'-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperidin^-yl}carbamate. MS (ES) m/z 447.2 ([M+H]+); HRMS: calcd for C25H32CI2N2O ¦ 2.00 HCI, 518.1425; found (ESI), 447.1962. Example 153: 1-[1-(3',4'-dichloro-1,1'-biphenyl-3-yl)-2-piperazin-1-ylethyl]cyclobutanol dihydrochloride [0420] In an analogous manner to Example 1, step 1 tert-butyl 4-f(3-bromophenyl)(1-hydroxvcyclobutyl)acetvlipiperazine-i -carboxvlate was prepared (3-bromophenyl)(1-hydroxycyclobutyl)acetic acid (Reference Example 1-j) and ferf-butyl 1- 139 WO 2005/037207 PCT/US2004/033730 piperazinecarboxylate. HRMS: calcd for C21H29BrN2O4, 452.1311; found (ESl_FT), 453.13746. [0421] In an analogous manner to Example 135, step 2 tert-butvl 4-[2-(3-bromophenvl-2-(1-hvdroxvcvcfobutvl)ethvnpiperazine-1-carboxvlate was prepared from tert-butyl 4-[(3-bromophenyl)(1 -hydroxycyclobutyOacetyljpiperazine-i -carboxylate and 3,4-dichloro phenyl boronic acid. [0422] In an analogous manner to Example 135, step 3 tert-butyl 4-[2-(3'.4'-dichloro-biphenyl-3-ylV2-(1-hydroxycyclobuty))ethyl]piperazine-1-carboxylate was prepared from tert-butyl 4-[2-(3-bromopheny!)-2-(1 -hydroxycyclobutyl)ethyl]piperazine-1 -carboxylate and 3,4-dichloro phenyl boronic acid. [0423] In an analogous manner to Example 135, step 4 1-[1-(3'.4'-dichforo-1,1'-biphenyl-3-yl)-2-piperazin-1-yIethyi]cyclobutanol dihydrochloride was prepared from tert-butyl 4-[2-(3',4'-dichioro-biphenyl-3-yl)-2-(1-hydroxycyclobutyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 405.1499 ([M+H]+); HRMS: calcd for C22H26CI2N2O ' 2.00 HCI, 476.0956; found (ESI), 405.1499.' Example 154: 1 -[1 -( 1 -methvl-1 H-indol-3-yl)-2-piperazin-1 -vlethyl]cvclohexanol dihydrochloride [0424] In an analogous manner to Example 1, step 1 tert-butyl 4-IY1- hvdroxycyclohexyl)(1-methyl-1H-indol-3-yl)acetynpiperazine-1-carboxylate was prepared from (1-methyl-1H-indol-3-yl) (1-hydroxycylclohexyl) acetic acid (Reference Example 1-xx) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 456 ([M+H]+); HRMS: calcd for C2SH37N3O4, 455.2784; found (ESI_FT), 456.28501. 140 WO 2005/037207 PCT/US2004/033730 [0425] In an analogous manner to Example 1, step 2 1 -[ 1 -(1 -methyl-1 H-indol-3-vl)2-piperazin-1 -vlethvncvclohexanol dihydrochloride was prepared from tert-butyl 4-[(1-hydroxycyclohexyl)(1 -methyl-1 H-indol-3-yl)acetyl]piperazine-1-carboxy!ate. MS (ES!) m/z 342 ([M+H]+); HRMS: calcd for C21H31N3O • 2.00 HCI, 413.2001; found (ESLFT), 342.25347 Example 155:1-p-(1H-indol-3-yl)-2-piperazin-1-ylethyHcyclohexanol dihydrochloride [0426] in an analogous manner to Example 1, step 1 tert-butvl 4-[(d- hydroxycy clohexyl) ( 1 -(tert-butyl-dimethyl-silanylH H-indol-3-yl)acetynpiperazine-1 - carboxvlate was prepared from (1-(tert-Buty!-dimethy!-silanyl)-1H-indol-3-yl) (1-hydroxycyiclohexyl) acetic acid (Reference Example 1-yy) and tert-butyl 1-piperazinecarboxylate. [0427] In an analogous manner to Example 1, step 2 1 -[1 -(1 H-indol-3-yl)-2-piperazin-1 -yiethyilcyclohexanol dihydrochloride was prepared from tert-butyl 4-[(1-hydroxycyc!ohexyl)(1 -(tert-butyl-dimethyl-silanyl)-i H-indoI-3-yl)acetyl]piperazine-1 -carboxylate. MS (ESI) m/z 328 ([M+H]+); HRMS: calcd for C20H29N3O • 2.00 HCI, 399.1844; found (ESLFT), 328.23696 Example 156:1 -[1 -(2-chlorothien-3-yl)-2-piperazin-1 -ylethylicyclohexanol 141 dihydrochloride WO 2005/037207 ( PCT/US2004/033730 [0428] In an analogous manner to Example 141, step 1 (2-chlorothien-3-vl)acetic acid was prepared from 2-thiophene acetic acid and 1 equivalent of N-chlorosuccinimide. MS (ESI)^/z 175/177 ([M+H]+); In an analogous manner to Example 1, step 1 tert-butyl 4-f(2-chlorothien-3-yl)acetvl1piperazine-1-carboxvlate was prepared from (2-chlorothien-3-yl)acetic acid_and tert-butyl 1-piperazinecarboxylate. MS (ES) m/z 289.0 ([M+H-C4H8]+); HRMS: calcd for C15H21CIN2O3S, 344.0961; found (ESI), 345.1057. [0429] In an analogous manner to Example 141, step 3 tert-butyl 4-f(2-chlorothien-3-yl)(1 -hydroxycyclohexyDacetvllpiperazine-i -carboxylate was prepared from tert-butyl 4-[(2-chlorothien-3-yl)acetyl]piperazine-1-carboxylate and cyclohexanone. [0430] In an anlogous manner to Example 135, step 2 tert-butyl 4-f2-(2-chlorothien-3-yl)-2-( 1 -hvdroxvcyclohexvl)ethvl1piperazine-1 -carboxylate was prepared from tert-butyl' 4-[(2-chlorothien-3-yl)(1-hydroxycyclohexyl)acetyI]piperazine-1-carboxylate. MS (ESI) m/z 429/431 ([M+H]+); HRMS: calcd for C2iH33ClN2O3S, 428.1900; found (ESI), 429.1967 [0431] In an analogous manner to Example 135, step 4 1 -f 1 -(2-chlorothien-3-vO-2-piperazine-i-vlethvlicvclohexanol 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'c16H25CIN2OS • 2.00 HCI, 400.0910; found (ESI), 329.1442. Example 157: 1 -f1 -(1.1 '-biphenyl-4-yl)-2-piperazin-1 -ylethvncyclohexanol ui dihydrochloride WO 2005/037207 [0432] In an analogous manner to Example 1, step 1 tert-buty hydro^cyclohexynacetyliDiperazine-i-carboxvlate was pi hydroxycyclohexyl)(1,1'-biphenyl-4-yl)acetic acid (Reference Ex butyl 1-piperazinecarboxylate. MS (ESI) m/z 479 ([M+HJ+); Anal. C, 72.77; H, 8.00; N, 5.85. Found: C, 72.69; H, 8.39; N, 5.80. [0433] In an analogous manner to Example 13, step 2 1-f1 piperazin-1 -vlethylicyclohexanol dihydrochloride was prepared f biphenyI-4-yl(i-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. ([M+H]+) HRMS: calcd for C24H32N2O . HCl, 400.2281; found (ESI_ Example 158: 1-[1-(1,1'-biphenyl-4-yl)-2-(4-methylpiperazin-1-yk dihydrochloride [0434] in an analogous manner to Example 24, 1-f1-(1,1'- methylpiperazin-1 -yl ethylicyclohexanol dihydrochloride was prepan biphenyl-4-yl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 157). ([M+H]+); HRMS: calcd for C25H34N2O • HCl, 414.2438; found (ESI_FT Example 159:1-[1 -(5-chlorothien-3-yi)-2-(4-methylpiperazin-1-yl)eth 143 dihydrochloride WO 2005/037207 PC77US2004/033730 [0432] In an analogous manner to Example 1, step 1 tert-buM4-M.1'-biphenvl-4-vlH-hydroxvcvclohexvOacetvnpiperazine-i-carboxvlate was prepared from (1-hydroxycyclohexyl)(1,1'-biphenyl-4-yl)acetic acid (Reference Example 1-zz) and tert-butyl 1-piperazinecarboxylate. MS (ESI) m/z 479 ([M+H]+); Anal. Caicd for C29H38N2O4: C, 72.77; H, 8.00; N, 5.85. Found: C, 72.69; H, 8.39; N, 5.80. [0433] In an analogous manner to Example 13, step 2 1-f 1 -(1.1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyllcvclohexanol dihydrochloride was prepared from tert-butyl 4-[1,1'-bfpheny!-4-yl(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate. MS (ESI) m/z 365 ([M+H]+) HRMS: calcd for C^HsaNbO . HCI, 400.2281; found (ESI_FT), 365.25908. Example 158: 1-[1-(1,1l-biphenyl-4-yl)-2-(4-methylpiperazin-1-ylethyl]cyclohexanol dihydrochioride [0434] In an analogous manner to Example ,24, 1-f1-(1.1'-biphenyl-4-vl)-2-(4- methvlpiperazin-1-vtethvncyclohexanol dihydrochloride was prepared from 1-[1-(1,1-biphenyl-4-yl)-2-piperazin-1-ylethyl]cyc!ohexano! (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 143 dihydrochloride WO 2005/037207 PCT/US2004/033730 [0435] In an analogous manner to Example 24, 1 -f1 -(5-chlorothien-3-vl)-2-f4-methy)piperazin-1 -vDethvncyclohexanol dihydrochloride was prepared from 1-[1-(5-chlorot^Len-3-yl)-2-piperazin-1-ylethyl]cyclohexanol (see Example 144). MS (ES) m/z 343.2 (fM+H]+); HRMS: calcd for C:7H27CIN2OS. 2.00 HCI, 414.1066; found (ESI), 343.1596. Example 160: 1-[1-(3-cyanophenyi)-2-piperazin-1-y!ethyl]cyclohexanoi dihydrochloride [0436] Step 1: A mixture of ferf-butyl 4-[2-(3-bromophenyl)-2-(1- hydroxycyclohexyl)ethyl]piperazine-1-carboxyiate (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(dipheny!phosphino)ferrocene (55 mg, 0.100 mmol), and zinc dust (16 mg, 0.25 mmol) in anhydrous A/,/V-dimethylformamide (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%) f erf-butyl 4-F2-(3-cvanophenyl)-2-(1 -hvdroxvcvclohexyPethvlipiperazine-i-carboxvlate as a yellow solid. MS (ESI) m/z 414 ([M+H]+); HRMS: calcd for Ca^NsOa, 413.2678; found (ESI), 414.2745. [0437] Step 2: In an analogous manner to Example 135, step 4,1 -[1 -(3-cyanophenvl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride was prepared from tert-buty\ 4-[2-(3-cyanophenyl)-2-(1-hydroxycyclohexyl)ethyi]piperazine-1-carboxylate. MS (ESI) m/z 314 ([M+H]+); HRMS: calcd for CigH27N3O • 2.00 HCi, 385.1688; found (ESI), 314.2225. 144 WO 2(105/037207 PCT/US2004/033730 Exampfej61:1-[1-(3-cyanophenyl)-2-(4-methylpiperazin-1-yI)ethyl]cyclohexanoI dihydrochloride [0438] In an analogous manner to Example 24, 1 -H -(3-cvanophenvl)-2-(4- methylpiperazin-1 -vOethvncyclohexanol dihvdrochloride was prepared from 1-[1-(3-cyanophenyl)-2-piperazin-1-ylethy!]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]cycIohexanol dihydrochloride [0439] Step 1: A mixture of te/f-butyl 4-[2-(3-bromophenyl)-2-(1 - hydroxycyclohexyl)ethy!]piperazine-1-carboxylate (see Example 135, step 2) (141 mg, 0.300 mmol), tributyl(viny!)tin (114 mg, 0.360 mmol, 1.2 equivalent), and tetrakis(triphenylphosphine)pal!adium (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-butvl 4-f2-(1- 145 WO 2005/037207 PCT/US2004/033730 hvdroxvcvc>ohexvl)-2-(3-vinvlphenvl)ethvnpiperazine-1-carboxylate as a viscous colorless oil. MS (ES) m/z 415.4 ([M+H]+); HRMS: calcd for C25H3SN2O3, 414.2882; found (ESI), 415.2966. [0440] Step 2: In an analogous manner to Example 135, step 4, 1-f2-piperazin-1-vl-1-(3-vtny(phenvl)ethvncvclohexanol dihvdrochloride was prepared from terf-butyl 4-[2-(1-hydroxycyclohexyl)-2-(3-vinylpheny1)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 315 ([M+KT); HRMS: calcd for C20H30N2O ¦ 2.00 HCI, 386.1892; found (ESI), 315.242. Example 163: 1-[2-piperaz/n-1-yl-1-(4-vinylphenyl)ethyI]cyclohexanol dihydrochloride [0441] in an analogous manner to Example 1, step 1 te/f-butyl 4-[Y4-bromophenyl)(1-hvdroxvcvclohexvDacetvllpiperazine-1-carboxylate was prepared from (4-bromophenyl)(1-hydroxycyclohexyl)acetic acid (Reference Example 1-h) and ferf-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. [0442] In an analogous manner to Example 135, step 2, fert-butyl 4-f2-(4- bromophenvl)-2-(1-hvdroxvcyclohexv0ethynpiperazine-1-carboxylate was prepared from fe/t-butyl 4-[(4-bromophenyl)(1-hydroxycycIohexyl)acetyI]piperazine-1-carboxylate. MS (ESI) m/z467/469 ([M+H]+). [0443} In an analogous manner to Example 162, step 1, fe/t-butyl 4-f2-(1- hvdroxvcyclohexvl)-2-(4-vinvlphenyl)ethvnpiperazine-1-carboxylate was prepared from fe/t-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyI)ethyl]piperazine-1-carboxylate. MS (ES) m/z 415.4 ([M+H]+); HRMS: calcd for 025^8^03, 414.2882; found (ESI), 415.2975. 146 WO 2005/037207 PCT/US2W4/033730 [0444] In an analogous manner to Example 135, step 4, 1 -r2-pjperazin-1 -vl-1 -(4-vinvlphanyl)ethvncvclohexano[ dihvdrochloride was prepared from tert-buiyl 4-[2-(1-hydroxycyclohexyl)-2-(4-vinylphenyI)ethyI]piperazine-1-carboxylate. MS (ES) m/z 315.3 ([M+H]+); HRMS: calcd for C2oH3oN20 2.00 HCI, 386.1892; found (ESI), 315.2424. Example 164: 1 -[2-piperazm-1 -yl-1 -(4-prop-1 -ynylphenyl)ethyl]cyclohexanol dihydrochloride [0445] In an analogous manner to Example 162, step 1, tetf-butyl 4-f2-(1- hvdroxvcvclohexvl)'2-(4-prop-1-ynylphenvl)ethvnpiperazine-1-carboxylate was prepared from ferf-butyl 4-[2-(4-bromopheny!)-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 CaeHssNaOa, 426.2882; found (ESI), 427.2945. [0446] In an analogous manner to Example 135, step 4, 1 -f2-piperazin-1 -yl-1 -(4-prop-1 -ynvlphenypethyncvclohexanol dihydrochloride was prepared from fe/f-butyl 4-[2-(1-hydroxycyclohexyl)-2-(4-prop-1-ynylphenyl)ethy!]piperazine-1 -carboxylate. MS (ESI) m/z 327 ([M+Hf); 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-yiethyl]cyclohexanol dihydrochloride 147 WO 2005/037207 ; PCT/LS20O-I/033730 [0447] Step 1: In an analogous manner to Example 135, step 3, tort-butyl 4-f2-C2'-chloro-1,1'-biphenvl-4-vn-2-C1-hvdroxvcvclohexvnethvnpiperazine-1-carboxvlate was prepared from terf-butyl 4-[2-(4-bromophenyl)-2-(1 -hydroxycyclohexyl)ethyl]piperazine-1-carboxylate {see Example 163, step 2) using 2-chIorophenylboronic acid. MS (ESI) m/z 499 ([M+HD; HRMS: calcd for CggHagCINaOs, 498.2649; found (ESI), 499.2745. [0448] Step 2: In an analogous manner to Example 135, step 4, 1-f1-(2'-chloro-1.1'-biphenvl-4-vl)-2-piperazin-1-vlethyllcyclohexanol diriydrochloride was prepared from ferf-butyl 4-[2-(2'-chloro-1,1 l-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1 -carboxylate. MS (ESI) m/z 399 ([M+H]+); HRMS: calcd for C24H3iC!N2O 2.00 HCI, 470.1658; found (ESI), 399.2200. Example 166: 1 -[1 -(3'-fluoro-1,1 '-biphenyI-4-yl)-2-piperazin-1 -ylethyl]cyclohexanol dihydrochloride [0449] In an analogous manner to Example 135, step 3, fetf-butyl 4-[2-(3'-fluoro-1.1'-biphenyl-4-yl)-2-(1-hvdroxycvdohexv0ethyllpiperazine-1-carboxylate was prepared from te/f-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]+). 148 WO 2005/037207 PCT/US2004/0JJ7J0 [0450] In an analogous manner to Example 135, step 4,1 -f 1 -(3'-f[uoro-1,1 '-biphenyl-4-yl)-2-piperazin-1 -ylethvlicyclohexanol dihydrochloride was prepared from terf-butyl 4-[2-(3'-fluorGS^1'-biphenyl-4-yl)-2-(1-hydroxycyclohexyl)ethy[]piperazine-1-carboxylate. MS (ES) m/z 383.3 ([M+H]+); HRMS: calcd for C24H3iFr\l2O • 2.00 HCI, 454.1954; found (ESI), 383.2494. Example 167:1 -f 1 -(3'-ch(oro-1,1 '-biphenvl-4-vO-2'Piperazin-1 -ylethvflcvclohexanoi dihydrochloride [0451] In an analogous manner to Example 135, step 3, fert-butvl 4-f2-(3'-ch(oro-1.1'-biphenyl-4-yl)-2-(1-hvdroxycyclohexyl)ethvnpiperazine-1-carboxylate was prepared from fe/t-butyl 4-[2-(4-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (see Example 163, step 2) using 3-chlorophenyIboronic acid. MS (ES) m/z 499.3 ([M+H]+); HRMS: calcd for CagHssCINaOs, 498.2649; found (ESI), 499.2738. [0452] In an analogous manner to Example 135, step 4, 1-F1 -(3'-chloro-1.1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyncyclohexanol dihydrochloride was prepared from fe/t-butyl 4-[2-(3'-chloro-1,V-biphenyl-4-yl)-2-(1-hydroxycyc!ohexyl)ethyl]piperazine-1-carboxylate. MS (ESI) m/z 399/401 ([M+H]1); HRMS: calcd for C24H31CIN2O " 2.00 HCI, 470.1658; found (ESI), 399.2211. Example 168: 1 -f1 -(3'-cyano-1,1 '-biphenyl-4-vO-2-piperazjn-1 -ylethyncyclohexanol dihydrochloride 149 WO 2005/037207 PCT/IS2004/033730 [0453] In an analogous manner to Example 135, step 3, tert-butvi 4-f2-(3'-cyano-1.1 '-biphenvl-4-vl)-2-(1-hvdroxvcvclohexvl)eihyllpiperazine-1-carboxvlate was prepared from fe/f-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+H]+). [0454] In an analogous manner to Example 135, step 4, 1 -f1 -(3'-cyano-1.1 '-biphenyl-4-yl)-2-piperazin-1 -ylethyncyclohexanol 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+H]+); HRMS: calcd for C25H31N3O 2.00 HCI, 461.2001; found (ESI), 390.2532. Example 169: 1-[1-(3'-nitro-1,1'-biphenvl-4-yl)-2-piperazin-1-ylethyncyclohexanol dihydrochloride [0455] In an analogous manner to Example 135, step 3, fe/t-butyl 4-[2-(1- r)ydroxycyclohexyl)-2-(3'-nitro-1,1 '-biphenyi-4-yl)ethynpiperazine-1 -carboxylate was prepared from te/f-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]+). 150 WO 2005/037207 PCT/US2004/03373-1-fF4-(benzv{oxv)-3-chlorophenvnn-hvdroxvcvclohexvl)acetvnDiperidin-3-vl}carbamate was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyciohexyt)acetic acid (Reference Example 1-eee) and (S)-(+)-3-t-butoxycarbony!aminopiperidine (Moon, S.; Lee, S., Synth. Commun. 1998, 28(21), 3919-3926.) MS (ES) m/z557.1 [05O2] In an analogous manner to Example 13, step 2,1 -(1 -r4-(benzvloxv)-3-chlorophenvll-2-f(3S)-3-(methvlamino)piperidin-1-vnethvl}cvclohexanol dihvdrochloride was prepared from ferf-butyl {(3S)-1-[[4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetyl]piperidin-3-yI}carbamate MS m/z457; HRMS: calcdfor C27H37CIN2O2 + H, 457.26218; found (ESI, [M+H]+), 457.2619 168 Example 196:1 -(2-f(3S)-3-aminopiperidin-1 -yli-1 -r4-fbenzvloxv)-3-chlorophenyliethvllcvclohexanol dihvdrochloride WO 2005/037207 PCT/US2004/033730 [0503] In an analogous manner to Example 1, step 1, fert-butvl f(3SH-fr4-(benzvloxv) -3-chlorophenvlin -hvdroxvcydohexvDacetvnpiperidin-S-vDcarbamate was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetic acid (Reference Example 1-eee) and (S)-(+)-3-t-butoxycarbony!aminopiperidine (Moon, S.; Lee, S., Synth. Commun. 1998, 28(21), 3919-3926.) MS (ES) m/z557.1 [0504] Jn an analogous manner to Example 1, step 2,1-(2-f(35V3-aminopiperidin-1 -vn-1-f4-(benzvloxv)-3-chlorophenvnethvt)cvclohexanoIdihvdrochloride was prepared from tert-buty\ {(3S)-1-[[4-(benzyioxy)-3-chlorophenyl](1- hydroxycycIohexy!)acety!]piperidin-3-yl}carbamate. MS m/z443; HRMS: calcd for C26H35CIN2O2 + H, 443.24653; found (ESI, [M+H]+), 443.2482. Example 197:1-(1-r4-(benzvloxv)-3-chlorophenvll-2-f(3^-3-(dimethvlaminoipiperidin-1- yliethvDcvclohexanol dihydrochloride [0505] In an analogous manner to Example 36,1 -(1 -r4-(benzvloxv)-3-chlorophenvn-2-f(3S)-3-fdimethvlamino)piperidin-1-vllethvl)cvclohexano)dihvdrochloride was prepared from 1 -{2-[(3.S)-3-aminopiperidin-1 -yl]-1 -[4-(benzyloxy)-3- chlorophenyl]ethyl}cyclohexanolj[See Example 196). HRMS: calcd for C28H39CIN2O2 + H, 471.27783; found (ESI, [M+H]+), 471.2766. Example 198: 1-1-(1-(3-chlorophenvn-2-f(3g)-3-(methvlamino')pvrrolidin-1-vnethvDcyclohexanol dihydrochloride 169 WO 2005/037207 PCT/US2004/033730 [0506] In an analogous manner to Example 1, step 1, terf-butvl (f3S)-1-f(3-chlorophenvDd-hvdroxvcvclohexvliacetvnDvrrolidin-S-vDcarbamate was prepared from (3-chlorophenyl)(1-hydroxycycIohexyl)acetic acid (Reference Example 1a) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 437.0 [0507] In an analogous manner to Example 13, step 2,1 -(1 -C3-chlorophenvlV2-F(3S)-3-fmethvlamino)pvrrolidin-1-vnethvl>cyclohexanoldihvdrochloride was prepared from te/?-butyl {(3S)-1 -[(3-chlorophenyl)(1 -hydroxycyclohexyl)acetyl]pyrrolidin-3-yl}carbamate MS (ES) m/z337.2; HRMS: calcd for C19H29CIN2O + H, 337.20467; found (ESI, [M+H]+), 337.2034. Example 199:1 -(1 -(3-chlorophenvl)-2-r(35)-3-(dimethvlaminotovrrolidin-1 -vnethvDcvclohexanoldihydrochloride [0508] In an analogous manner to Example 36,1-(1-(3-chlorophenvn-2-[(3S)-3-(dimethvlamino)pvrrolidin-1-vnethvl)cvcloh3xanotdihvdrochloride 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-[(3/?)-3-(methv[amino)pvrrolidin-1 -vnethvDcvclohexanoldihvdrochloride 170 WO 2005/037207 PCT/US2004/033730 [0509] In an analogous manner to Example 1, step 1, ferf-butvl f(3ffl-1-f(3-chlorophenvl)n-hvdroxvcvclohexvnacetvnpvrrolidin-3-v^carbamate was prepared from (3-chlorophenyI)(1-hydroxycycIohexyl)acetic acid (Reference Example 1a) and (3R)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS m/z 437 [0510] In an analogous manner to Example 13, step 2,1 -(1 -(3-chlorophenvl)-2-f(3/7)-3-("rnethvlamino)pvrrolidin-1-vnethvl)cvclohexanoldihvdrochloride was prepared from tert-butyl {(3/?)-1 -[(3-chlorophenyl)(1 -hydroxycyclohexyl)acety!jpyrrolidin-3-yl}carbamate MS (ES) m/z337.1; HRMS: calcd for C19H29CIN2O + H, 337.20467; found (ESI, [M+Hj+), 337.2043. Example 201:1-f2-f(3fl)-3-aminopvrrolidin-1-vl]-1-(3-chlorophenvl)ethvncvclohexanol dihydrochloride [0511] In an analogous manner to Example 1, step 1, fe/f-butvl ((3f?V1-ff3-chlorophenvn(1-hvdroxvcvclohexvl)acetvnpvrrolidin-3-yl}carbamate was prepared from (3-chlorophenyl)(1-hydroxycyc!ohexyl)acetic acid (Reference Example 1a) and (3R)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS m/z 437 [0512] In an analogous manner to Example 1, step 2, 1-[2-rf3f?)-3-aminopyrrolidin-1-yli-1 -(3-chlorophenvOethvncyclohexanol dihydrochloride was prepared from ferf-butyl 171 WO 2005/037207 PCT7US2004/033730 {(3fl)-1 -[(3-chlorophenyl)(1 -hydroxycyclohexyl)acetyl]pyrrolidin-3-yI}carbamate MS (ESI) /T7/Z323; HRMS: calcd for C18H27CIN2O + H, 323.18901; found (ESI, [M+H]+), 323.1895. Example 202:1 -(1 -(3-chlorophenvlV2-IY 3R)-3-( dimethvlamino)pyrrolidin-1 -vnethyllcvclohexanol dihvdrochloride [0513] In an analogous manner to Example 36,1 -(1 -(3-chlorophenvl)-2-f(3fl)-3-(d"!methylamino)pvrrolidin-1-vnethvl)cvclohexanol dihvdrochloride was prepared from 1-[2-[(3f?)-3-aminopyrroiidin-1 -yl]-1-(3-chlorophenyl)ethyl]cyclohexanol (See Example 201). MS (ESI) m/z35V, HRMS:.calcd for C20H31CIN2O + H, 351.22031; found (ESI, [M+H]+), 351.2193. Example 203: H2-r(35)-3-(methvlamino)pyrrolidin-1-vn-1-(2-naphthvl)ethvllcvclohexanol dihvdrochloride [0514] In an analogous manner to Example 1, step 1, te/f-butvl ((3S)-1-1Y1-hvdroxvcyclohexvl)(2-naphthvl)acetvnpvrrolidin-3-vl)carbamate was prepared from (1-hydroxycyclohexyl)(2-naphthyl)aceticacid (Reference Example 1q) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS m/z 437 [0515] In an analogous manner to Example 13, step 2, 1 -F2-f(3S)-3-(methvlamino)pyrrolidin-1-vn-1-(2-naphthvl)ethvncvclohexanol dihvdrochloride was prepared from tert-butyl {(3S)-1-[(1-hydroxycyc!ohexyl)(2-naphthyl)acety!]pyrrolidin-3- 172 WO 2005/037207 PCT/US2004/033730 yljcarbamate MS (ESI) m/z 353; HRMS: calcd for C23H32N2O + H, 353.25929; found (ESI, [M+HD, 353.2582. Example 204:1 -r2-IY3S)-3-aminopvrrolidin-1 -yti-1 -(2-naphthvOethvncvclohexanol dihydrochloride [0516] In an analogous manner to Example 1, step 1, te/t-butvl U3S)-1-I(1-hydroxycyclohexyl)(2-naphthy0acetvl]pyrrolidin-3-vl}carbamate was prepared from (1-hydroxycyclohexyl)(2-naphthy!)acetic acid (Reference Example 1q) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS m/z 437 [0517] In an analogous manner to Example 1, step 2.1 -F2-f(3S)-3-aminopyrrolidin-1 -vH-1 -(2-naphthvl)ethvPcyclohexanol dihydrochloride was prepared from tert-butyl {(3S)-1-[(1-hydroxycyclohexyl)(2-naphthyl)acetyl]pyrrolidin-3-yl}carbamate MS (ESI) m/z 339; HRMS: calcd for C22H30N2O + H, 339.24364; found (ESI, [M+H]+), 339.2441. 173 Example 205:1-f2-r(3S)-3-(dimethvlamino)pvrrolidin-1-vn-1-^2-naphthvQethvncvclohexanol dihydrochloride WO 2005/037207 PCT/US2004/033730 [0518] In an analogous manner to Example 36,1-f2-f(3SV3-(dimethvlaminotovrrolidin-1 -vlj-1 -f2-naphthvl)ethvncvclohexanol dihvdrochloride was prepared from 1-[2-[(3S)-3-amin6pyrrolidin-1-yl]-1-(2-naphthyl)ethyl]cyclohexanol (See Example 204). MS (ES).m/z 367.1; HRMS: calcd for C24H34N2O + H, 367.27494; found (ESI, [M+H]+), 367.2729. Example 206:1-f2-r(3SV3-(methvlamino)pvrrolidin-1-vl1-1-n- naphthvDethvncvclohexanol dihvdrochloride [0519] In an analogous manner to Example 1, step 1, tert-buM f(3S)-1-rn-hvdroxvcvclohexvl)n-naphthvl)acetvnpvrrolidin-3-vl)carbamate was prepared from (1-hydroxycyclohexyl)(1-naphthyl)acetic acid (Reference Example 1-e) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 453.2 [0520] In an analogous manner to Example 13, step 2,1 -C2-rf3S)-3-(methvlamino)pvrrolidin-i -vli-1 -f 1 -naphthvDethvllcvclohexanol dihvdrochloride was prepared from fe/t-butyl {(3S)-1-[(1-hydroxycyclohexyl)(1-naphthyl)acetyl]pyrrolidin-3-yl}carbamate MS (ESI) m/z 353; HRMS: calcd for C23H32N2O + H, 353.25929; found (ESI, [M+H]+), 353.2589. Example 207: 1 -f2-f(3S)-3-aminopyrrolidin-1 -vIM -(1 -naphthyDethylicyclohexanol :74 dihvdrochloride WO 2005/037207 PCT/US2004/033730 [0521 ] In an analogous manner to Example 1, step 1, ferf-butvl((3S)-1-rn-hvdroxVJ^clohexvDd-naphthvnacetvnpvrrolidin-S-vDcarbamate was prepared from (1-hydroxycyclohexyl)(1-naphthyl)acetic acid (Reference Example 1e>and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 453.2 [0522] In an analogous manner to Example 1, step 2,1 -f2-f (3S)-3-aminopyrrolidin-1 -vIM-M -naphthvPethvUcvclohexanol dihvdrochloride was prepared from te/t-buty! {(3S)-1-[(1-hydroxycyclohexyl)(1-naphthyl)acetyl]pyrrolidin-3-yl}carbamate MS (ESI) m/z 339; HRMS: calcd for CazHsoNaO + H, 339.24364; found (ESI, [M+H]+), 339.2421. Example 208:1-r2-rf3S)-3-fdimethvlamino)pvrrolidin-1-vn-1-(1-naphthvDethvncvclohexanol dihvdrochloride [05233 In an analogous manner to Example 36,1-f2-f(3SV3-(dimethvlarnino)pyrrolidin-1 -vll-1 -(1-naphthvflethvncvclohexanol dihvdrochloride was prepared from 1-[2-[(3S)-3-aminopyrrolidin-1-yl]-1-(1-naphthyl)ethyl]cyclohexanol (See Example 207). MS (ES) m/z 367.1; HRMS: calcd for C24H34N2O + H, 367.27494; found (ESI, [M+H]+), 367.275. Example 209: 1-(1-r4-(benzvloxvV3-chlorophenvH-2-r(3S)-3-(methvlamino)pyrrolidin-1- 175 yliethvDcvclohexanol dihvdrochloride WO 2005/037207 PCT/US2004/033730 [0524] In an analogous manner to Example 1, step 1, fe/f-butvl (f3S^-1-rr4-(benzvloxvj-S-chlorophenvnd-hvdroxvcvclohexvDacetvnpyrrolidin^-vDcarbamate was prepared from [4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyI)acetic acid (Reference Example 1 eee) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 543.0 [0525] In an analogous manner to Example 13, step 2,1 -11 -[4-(benzvloxv)-3-chlorophenvn-2'r(3S)-3-(methvlamino)pvrrolidin-1-vnethvllcvclohexanoldihvdrochloride was prepared from tert-butyl {(3S)-1-[[4-(benzyloxy)-3-chlorophenyl](1-hydroxycyclohexyl)acetyl]pyrrolidin-3-yl}carbamate MS (ES) m/z 443.1; HRMS: calcdfor C26H35CIN2O2 + H, 443.24653; found (ESI, [M+H]+), 443.2449. 176 Example 210:1 -(2-f(3S)-3-aminopyrrolidin-1 -vli-1 -r4-(benzvloxv)-3-chlorophenvnethvllcvclohexanoldihvdrochloride WO 2005/037207 PCT/US2004/033730 [0526] In an analogous manner to Example 1, step 1, fe/t-butvl{(3S)-1-rr4-fbenzvlo)»sy)-3-chloroDhenvn(1-hvdroxvcvclohexvl)acetvnpvrro{idin-3-v()carbamatewas prepared from [4-(benzyloxy)-3-chlorophenyi](1-hydroxycyclohexyl)acetic acid (Reference Example 1eee) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 543. [0527] In an analogous manner to Example 1, step 2.1 -f2-r(3S)-3-aminopyrrolidin-1 -vn-1-r4-(benzvloxy)-3-chlorophenvl]ethvl)cyclohexano) dihydrochloride was prepared from terf-butyl {(3S)-1-[[4-(benzyIoxy)-3-chlorophenylXi- hydroxycyclohexyl)acetyl]pyrro!idin-3-yI}carbamate MS (ES) m/z429.0; HRMS: calcd for CasHssCINaOa + H, 429.23088; found (ESI, [M+Hf), 429.232. Example 211:14H4-(benzvloxv)-3-chlorophenvn-2-r(35)-3-(dimethvlamino)pyrrolidin-1- vnethvllcvclohexanoldihydrochloride [0528] In an analogous manner to Example 36, 1 -{1 -r4-(benzv(oxv)-3-chforophenvn-2-f(3S)-3-(dimethvlamino)pvrrolidin-1-vnethvl)cvclohexanoldihydrochloride was prepared from ^.1 -{2-[(3S)-3-aminopyrro!idin-1 -yl]-1 -[4-(benzyloxy)-3- chlorophenyl]ethyl}cyclohexanol_(See Example 210). MS (ES) m/z457.0; HRMS: calcd for C27H37CIN2O2 + H, 457.2621 8; found (ESI, [M+H]+), 457.2636. Example 212:1-{1-r4-(benzvloxv)phenvn-2-r(3S)-3-(methvlamino)pvrrolidin-1-vnethvllcyclohexanol dihydrochloride 177 WO 2005/037207 PCT/US2004/03373(l [0529] In an analogous manner to Example 1, step 1, ferf-butvl ((3S)-1-ff4-(benzvloxv)phenvl1(1-hvdroxvcvclohexyl)acetvnpvrroliclin-3-vl)carbamate was prepared from (4-benzyloxyphenyI)(1-hydroxycyclohexyl)acetic (Reference Example 1n) and (3S) (-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 509.0 [0530] In an analogous manner to Example 13, step 2, 1 -(1 -f4-(benzvloxv)phenvn-2-f(3S)-3-(methylamino)pyrrolidin-1 -vl]ethvl)cvclohexanol dihvdrochloride was prepared from terf-butyl {(3S)-1 -[[4-(benzyloxy)phenyl](1 -hydroxycyclohexyl)acetyl]pyrrolidin-3-yljcarbamate MS (ES) m/z 409.1; HRMS: calcd for C26H36N2O2 + H, 409.28550; found (ESI, [M+H]+), 409.2841 Example 213: 1-(2-r(3S)-3-aminopyrrolidin-1-vn-1-r4 (benzvloxy)phenYnethvl)cvclohexanol dihvdrochloride [0531] In an analogous manner to Example 1, step 1, ferf-butvl ((3S)-1-rF4-(benzvloxv)phenvnf1-hvdroxvcvclohexvnacetvnpvrrolidin-3-vl)carbamate was prepared from (4-benzyloxyphenyl)(1-hydroxycyclohexyl)acetic_(Reference Example 1n) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 509.0 [0532] In an analogous manner to Example 1, step 2, 1 -(2-f(3S)-3-aminopyrrolidin-1 -yli-1 -f4-(benzyloxv)phenynethyl}cvclohexanol dihvdrochloride was prepared from tert-butyl {(3S)-1 -[[4-(benzyloxy)phenyl](1 -hydroxycyclohexyl)acetyl]pyrrolidin-3- 178 WO 2005/037207 PCT/US2004/033730 yljcarbamate MS (ES) m/z395.1; HRMS: calcd for C25H34N2O2 + H, 395.26985; found (ESUM+H]+), 395.2696. Example 214:1-(t-f4-('benzvloxv)phenvrn-2-r(3S)-3-(dimethvlamino)pvrrolidin-1- vHethvltovclohexanoldihvdrochloride [0533] In an analogous manner to Example 36,1 -(1 -r4-(benzvloxv)phenvn-2-f(3S)-3-(dimethvlamino)pyrrolidin-1-vnethvl)cvclohe>canoldihvdrochloride was prepared from, 1-{2-[(3S)-3-aminopyrrolidin-1 -yl]-1 -[4-(benzyloxy)phenyl]ethyl}cyclohexanol (See Example 213). MS (ES) m/z423.1; HRMS: calcd for C27H38N2O2 + H, 423.30115; found (ESI, [M+H]+), 423.302 Example 215:1-(2-f(3S)-3-(methvlamino)pyrrolidin-1-vn-H3- (trifluoromethoxy)phenvllethvl)cvclohexanol 179 dihydrochloride WO 2005/037207 PCT/US2004/033730 [0534] In an analogous manner to Example 1, step 1, tert-butvl f(3S>-1-((1-hvdroxvcvclohexvnrs-^rifluoromethoxv^phenvnacetvDpvrrolidin-S-vDcarbamatewas prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1f) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 487.0 [05351 In an analogous manner to Example 13, step 2,1 -j"2-r(r3S)-3-(methvlamfno)pvrrolidin-1-vn-1-r3-(trifluoromethoxy)phenvl]ethvl)cvclohexanol dihvdrochloride was prepared from te/t-butyl ((3S)-1-{(1-hydroxycydohexyl)[3-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yI)carbamate MS (ES) m/z 387.1; HRMS: calcd for Cao^sFsNaOa + H, 387.22594; found (ESI, [M+H]+), 387.2255. Example 216: 1-(24(3S)-3-aminopyrrolidin-1-vn-1-r3-(trifluoromethoxv)phenvflethvl)cvclohexanol dihvdrochloride [0536] In an analogous manner to Example 1, step 1, tert-butyl ((3SH-U1-hvdroxvcvclohexvnf3-(trifluoromethoxv)phenvnacetvl)pvrrolid}n-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1f) and (3S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 487.0 [0537] In an analogous manner to Example 1, step 2,1 -(2-f (3S)-3-aminopyrrolidin-1 -vn-1-f3-(trifluoromethoxv)phenvllethvl)cvclohexanol dihvdrochloride was prepared from tert-butyl ((3S)-1 -{(1 -hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyi}pyrrolidin-3-yl)carbamate MS (ESI) m/z 373; HRMS: calcd for C19H27F3N2O2 + H, 373.21029; found (ESI, [M+H]+), 373.2106. Example 217:1 -(2-r(35)-3-(dimethvlamino)pyrrolidin-1 -vll-1 -f3-(trifluoromethoxv)phenvllethvl)cvclohexanol dihvdrochloride 180 WO 2005/037207 PCT/US2004/033730 [0538] In an analogous manner to Example 36, 1-(2-f(3S)-3-(rdimethvlamino)pyrrolidin-1-vl1-1-("3-(trifluoromethoxv)phenvnethvl)cyclohexanol dihvdrochloride was prepared from, 1 -{2-[(3S)-3-aminopyrrolidin-1 -yl]-1 -[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol (See Example 216). MS (ESI) /n/z401; HRMS: calcd for C21H31F3N2O2 + H, 401.24159; found (ESI, [M+H]+), 401.2413. Example 218:1-(2-f(3ffl-3-(methvlamino)pvrrolidin-1-vn-1-f3-(trifluoromethoxy)phenvnethvl)cvclohexanol dihvdrochloride [0539] In an analogous manner to Example 1, step 1, fert-butyl ((3F?)-1-((1-hydroxvcvclohexvl)f3-(trifluoromethoxv)phenvnacetvl}pvrrolidin-3-yl)carbamate was prepared from (1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetic acid (Reference Example 1f) and (3R)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine. MS (ES) m/z 487.0 [0540] In an analogous manner to Example 13, step 2, i-^-ffSffl-S-(methvlamino)pvrrolidin-1-vn-1-f3-(trifluoromethoxv>phenvnethvl)cvclohexanol dihvdrochloride was prepared from tert-buly\ ((3/?)-1 -{(1-hydroxycyclohexyl)[3-(trifluoromethoxy)phenyl]acetyl}pyrrotidin-3-yl)carbamate MS m/z 387; HRMS: calcd for C20H29F3N2O2 + H, 387.22594; found (ESI, [M+Hf), 387.225. 181 WO 2005/037207 PCT/US2004/033730 Example 219:1 -(2-f(3RV3-(dimethvlaminotoyrro)idin-1 -v)1-1 -F3-(trifluoromethoxv)phenvnethvl)cvclohexanoidihvctroch[oride [0541] In an analogous manner to Example 36,1 -f2-f(3 /?)-3-(dimethvlamino)pvrrolidin-1-vn-1-f3-(trifluoromethoxv)phenvnethv(lc The reaction was then allowed to warm to 25 °C where it was stirred for 45 minutes and was then re-cooled to -78 °C. Cyclopentyl bromide (0.76 mL, 7.1 rnmol) was then added via syringe, and the resulting mixture was stirred at -78 °C for 1 hour. The reaction mixture was allowed,to warm to 'room temperature and then stirred overnight. The reaction was then quenched by the addition of a saturated aqueous solution of ammonium chloride, and the tetrahydrofuran was removed in vacuo. The resulting residue was dissolved in a 2N aqueous solution of sodium hydroxide (30 mL) and washed with ethyl acetate (1x15 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 (3x15 mL), and the combined organic extracts were dried over magnesium sulfate, concentrated in vacuo and the product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% EtOAc/hexane to 40% EtOAc/hexane) to yield 1.08 g (79%) (3-chlorophenvnfcvclopentvl)acetic acid as a clear oil. HRMS: calcd for C13H15CIO2 - H, 237.06823; found (ESI, [M-H]-), 237.0682 ss)ln an analogous manner, (3-chlorophenvlKcvclohexvDacetic acid was prepared from 3-chlorophenylacetic acid and cyclohexylbromide. HRMS: calcd for CuHi7CIO2 -H, 251.0817; found (ESI, [M-H]-), 251.0849. tt) In an analogous manner, (3-chlorophenvO(cvcloheptvflacetic acid was prepared from 3-chlorophenylacetic acid and cycloheptylbromide. HRIV1S: calcd for Ci5H19CIO2-H, 265.0974; found (ESI, [M-H]'), 265.0985. uu)ln an analogous manner, (3-chlorophenvD(2-hvdroxvcvclohexvl)acetic acid was prepared from 3-chlorophenylacetic acid and cyclohexene oxide. HRMS: calcd for CuHiyCICVH, 267.0766; found (ESI, [M-H]'), 267.0779 186 Example 226: H2-(3-chlorophenvr)-2-cvclopentvlethvnpiperazine dihvdrochloride WO 2005/037207 PCT/US2004/033730 [0553] In an analogous manner to Example 1, step 1, tort-butyl 4-IY3-chloroph^vO(cvclopentvQacetvnpiperazine-1-carboxvlate was prepared from (3-chlorophenyl)(cyclopentyl)acetic acid (Reference Example 2-a) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C22H31CIN2O3+H, 407.2123; found (ESI, [M+H]+), 407.2094. [0554] In an analogous manner to Example 1, step 2, 1 -r2-(3-chlorophenvO-2-cyclopentylethyripiperazine dihvdrochloride was prepared from tert-butyl 4-[(3-chlorophenyl)(cyclopentyl)acetyl]piperazine-1-carboxylate HRMS: calcd for C17H25CIN2 + H, 293.17845; found (ESI, [M+HJ+), 293.1776 Example 227:1 -f2-(3-chlorophenvO-2-cvclopentvlethvn-4-methvlpiperazine dihvdrochloride [0555] In an analogous manner to Example 24, 1 -f2-(3-chlorophenvlV2-cyclopentvlethvn-4-rnethvlpiperazine dihvdrochloride was prepared from, 1-[2-(3-chlorophenyl)-2-cyclopentylethyl]piperazine (See Example 226). MS (ES) m/z 307.2; HRMS: calcd for C18H27CIN2 + H, 307.19410; found (ESI, [M+H]+), 307.1935. Example 228:1 -r2-f3-chlorophenvl)-2-cvclopentvlethvn-A/-methvlpiperidin-4-amine 187 dihvdrochloride WO 2005/037207 PCT/US2004/033730 [0556] In an analogous manner to Example 1, step 1, fert-butvl(1-f(3-chlord^9nvlWcvclopentvl)acetvlipiperidin-4-vl)carbamatewas prepared from (3-chlorophenyl)(cyclopentyl)acetic acid (Reference Example 2-a) and 4-N-Boc-arninopiperidine. HRMS: calcd for C23H33CIN2O3+H, 421.2280; found (ESI, [M+H]+), 421.2269. [0557] In an analogous manner to Example 13, step 2,1 -r2-(3-chlorophenvlV2-cvclopentvlethvn-A/-methvlpiperid)n-4-amine dihvdrochloride was prepared from tert-butyl (1-[(3-chlorophenyl)(cyclopentyl)acetyl]piperidin-4-yl}carbamate MS (ES> m/z 321.2; HRMS: calcd for C19H29CIN2 + H, 321.20975; found (ESI, [M+H]*), 321.2088. Example 229:1-r2-(3-chlorophenvn-2-cvclopentvlethvn-A/.A/-dimethvlpiperidin-4-amine dihvdrochloride [0558] In an analogous manner to Example 36,1 -r2-(3-chlorophenyl)-2-cvclopentvlethvn-A/,A/-dimethylpiperidin-4-amine dihvdrochloride was prepared from, 1-[2-(3-chlorophenyl)-2-cyclopentylethyl]-A/-methylpiperidin-4-amine.(See Example 228). MS (ES) m/z 335.2; HRMS: calcd for C20H31CIN2 + H, 335.22540; found (ESI, [M+H]+), 335.2243. 188 Example 230:1-f2-(3-chlorophenvn-2-cvclohexvlethvnpiperazine dihvdrochloride WO 2005/037207 PCT/US2004/U33730 [0559] In an analogous manner to Example 1, step 1, fert-butvl 4-IY3-chlorop1^f]hvlKcvclohexv0aceMipiperazine-1-carooxvlate was prepared from (3-chlorophenyl)(cyclohexyl)acetic acid (Reference Example 2-b) and tert-butyl 1-piperazinecarboxylate. HRMS: calcd for C23H33CIN2O3+H, 421.2280; found (ESI, [M+H]+), 421.2261. [0560j In an analogous manner to Example 1, step 2,1 -r2-(3-chlorophenvn-2-cyclohexylethvnpiperazine dihvdrochloride was prepared from tert-buty] 4-[(3-chlorophenyl)(cyclohexyl)acetyl]piperazine-1-carboxylate HRMS: calcd for C18H27CIN2 + H, 307.19410; found (ESI, [M+H]+), 307.1943. Example 231: 1 -r2-(3-chlorophenvO-2-cyclohexylethvl1-4-methvlpiperazine dihvdrochloride [0561] In an analogous manner to Example 24,1 -f2-(3-chlorophenvl)-2-cvclohexvlethvn-4-methvlpiperazine dihvdrochloride was prepared from, 1-[2-(3-chlorophenyl)-2-cyclohexylethyl]piperazine (See Example 230). MS (ES) m/z 321.2; HRMS: calcd for C19H29CIN2 + H, 321.20975; found (ESI, [M+H]+), 321.2108. Example 232:1 -f2-(3-chlorophenvl)-2-cvclohexvlethyll-A/-methvlpiperidin-4-amine dihvdrochloride [0562] In an analogous manner to Example 1, step 1, ferf-butvl (1-IY3-chlorophenvD(cvclohexvlWceWHpiperidin-4-vl}carbamate was prepared from (3- 189 WO 2005/037207 PCT/US2(KI4/03J73(l chlorophenyl)(cyclohexyl)acetic acid (Reference Example 2-b) and 4-N-Boc-amirSpiperidine. HRMS: calcd for C24H35CIN2O3 +H, 435.2436; found (ESI, [M+H]+), 435.2422. [0563] In an analogous manner to Example 13, step 2,1 -f2-(3-chlorophenvlV2-cyclohexvlethvl]-N-methvlpiperidin-4-am>ne dihydrochlortde was prepared from terf-butyl {1-[(3-chlorophenyI)(cycIohexyl)acetyl]piperidin-4-yl}carbamate MS (ES) m/z 335.3; HRMS: calcd for C2oH31CIN2 + H, 335.22540; found (ESI, [M+H]+), 335.2245. Example 233:1 -f2-(3-chlorophenvl)-2-cvclohexvlethvn-A/, A/-dimethvlpiperidin-4-amine dihvdrochloride [0564] In an analogous manner to Example 36,1 -r2-f3-chlorophenvn-2-cyclohexvlethvn-A/,A/-dimethylpiperidin-4-amine dihvdrochloride was prepared from, 1-[2-(3-chlorophenyl)-2-cyclohexylethyl]-A^-methylpiperidin-4-amine (See Example 232). HRMS: calcd forC2iH33ClN2 + H, 349.24105; found (ESI, [M+H]+), 349.2422. Example 234: 1-[2-(3-chlorophenvn-2-cvcloheptylethvnpiperazine dihvdrochloride [0565] In an analogous manner to Example 1, step 1, ferf-butyl 4-f (3-chlorophenvl)(cycloheptv0acefynpiperazine-1-carpoxvlate was prepared from (3- 190 WO 2005/037207 PCT/US2004/033730 2hlorophenyl)(cycloheptyl)acetic acid (Reference Example 2-c) and tert-butyl 1-piperazi^carboxylate. MS m/z379 [0566] In an analogous manner to Example 1, step 2,1 -f2-(3-chIorophenvl)-2-cycloheptylethvflpiperazine dihydrochloride was prepared from ferf-butyl 4-[(3-chlorophenyl)(cyclohepty!)acetyl]piperazine-1-carboxy!ate MS (ES) /7i/z321.2; HRMS: calcd for C19H29CIN2 + H, 321.20975; found (ESI, [M+H]+), 321.2105. Example 235: 1 -r2-(3-chlorophenvn-2-cvcloheptvlethv[l-4-methvlpiperazine dihydrochloride [0567] In an analogous manner to Example 24,142-(3-chlorophenvl)-2-cvcloheptvlethvlH-rnethvlpiperazine dihvdrochloride was prepared from, 1-[2-(3-chforopheny!)-2-cycIoheptylethyl]piperazine_(See Example 234). MS (ES) m/z 335.2; HRMS: calcd for C20H31CIN2 + H, 335.22540; found (ESI, [M+Hf), 335.2253. Example 236:1 -f2-(3-chlorophenvl)-2-cvcloheptvlethvn-A/-methvlpiperidin-4-amine 191 dihvdrbchloride