Indian Patents. 234746:PYRIDYL DERIVATIVES AS HUMAN STEAROYL-COA DESATURASE INHIBITORS

Title of Invention	PYRIDYL DERIVATIVES AS HUMAN STEAROYL-COA DESATURASE INHIBITORS
Abstract	PYRIDYL DERIVATIVES AS HUMAN STEAROYL-COA DESATURASE INHIBITORS The present invention relates to a compound of formula (I): as defined in the description and a stereoisomer, enantiomer or tautomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.

Full Text	PYRIDYL DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS FIELD OF THE INVENTION The present invention relates generafty tc the fieW of inhibitors of stearoyl-CoA desaturase, such as pyridine derivatives, and uses for such compounds in treating and/or preventing various human diseases nckxJng those mediated by stearoyl-CoA desaturase (SCD) enzymes, preferably SCD! esoeciaiy cfeeases related to elevated lipid levels, cardiovascular disease diabetes aoesry netabofec syndrome and the like. BACKGROUND OF THE INVENTION Acyl desaturase enzymes catalyze the taraatari of double bonds in fatty acids derived from either dietary sources or de novo synthesis in the liver. Mammals synthesize at least three fatty acid desaturases of Offering chain length specificity that catalyze the addition of double bonds at the detta-9 detta-5; and delta-5 positions. Stearoyl-CoA desaturases (SCDs) introduce a double bond in the C9-C10 position of saturated fatty acids. The preferred substrates are palmrtoyl-CoA (16:0) and stearoyl-CoA (18:0), which are converted to palmitoleoyl-CoA (16:1) and oleoyl-CoA (18:1), respectively. The resulting mono-unsaturated fatty acids are substrates for incorporation into phospholipids, triglycerides, and cholesteryl esters. A number of mammalian SCD genes have been cloned. For example, two genes have been cloned from rat (SCD1, SCD2) and four SCD genes have been isolated from mouse (SCD1, 2, 3, and 4). Whie the basic biochemical role of SCD has been known in rats and mice since the 1970s (Jeffcoat R. et a/., Elsevier Science (1984), Vol, 4, pp. 85-112; de Antueno, RJ. Upkis (1993), Vol. 28, No. 4, pp. 285-290), it has only recently been directly implicated in human disease processes. A single SCD gene, SCD1, has been characterized in humans. SCD1 is described in Brownlie et a/, PCT published patent application, WO 01/62954, the disclosure of which is hereby incorporated by reference in its entirety. A second human SCD isoform has recently been identified, and because it bears little sequence homology to alternate mouse or rat isoforms it has been named human SCD5 or hSCD5 (PCT published patent appfcation, WO 02/26944, incorporated herein by reference in its entirety). To date, no small-moteculet drug-like compounds are known that specifically inhibit or modulate SCD activity. Certain long-chain hydrocarbons have been used historically to study SCD activity. Known examples include thia-fatty acids, cycbpropenoid fatty acids, and certain conjugated iinoteic acid Isomers. Specifically, c/s-12, frans-10 conjugated Iinoteic acid is believed to inhibit SCD enzyme activity and reduce the abundance of SCD1 mRNA whfie c?s-9 trans-l 1 conjugated linoleic acid does not Cycbpropenoid fatty acids, such as those found in stercula and cotton seeds, are also known to inhibit SCD activity Few example, sterculic acid (8-(2-octylcyclopropenyl)octanoic add) and mavafoc acid fM2-ocyteydopropenyI)heptanoic acid) are C18 and C16 derivatives of stercuoy and mafrvaioyl fatty acids, respectively, having cyclopropene rings at ther C9-C1C aostean These agents are believed to inhibit SCD enzymatic activity by direct rteradcr win ihe enzyme, thus inhibiting delta-9 desaturation. Other agents that may mi* SCD activity include thia-fatty acids, such as S-thiastearic acid (also caiec 3-noryihocctanoic acid) and other fatty acids with a sutfoxy moiety. These known modulators of detta-9 desaturase activity are not useful for treating the diseases and disorders linked to SCD1 biological activity. None of the known SCD inhibitor compounds are setective for SCD or defta-9 desaturases, as they also inhibit other desaturases and enzymes. The thia-fatty acids, conjugated linoleic acids and cyclopropene fatty acids (mafvalic acid and sterculic acid) are neither useful at reasonable physiological doses, nor are they specific inhibitors of SCD1 biological activity, rather they demonstrate cross inhibition of other desaturases, in particular the delta-5 and delta-6 desaturases by the cyclopropene fatty acids. The absence of small molecule inhibitors of SCD enzyme activity is a major scientific and medical disappointment because evidence is now compelling that SCD activity is directly implicated in common human disease processes: See e.g., Attie, A.D. ef a/., "Relationship between stearoyt-CoA desa&jrase activity and plasma triglycerides in human and mouse hypertriglyceridemia", J. Lipid Res. (2002), Vol. 43, No. 11, pp. 1899-907; Cohen, P. et a/., "Rote for stearoyt-CoA desaturase-1 in leptin-mediated weight loss", Science (2002), VoL 297. No. 5579, pp. 240-3, Ntambi, J. M. et a/., "Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity", Proc. Natl. Acad. Sci. USA. (2002), Vol. 99, No. 7. pp. 11482-6. The present invention solves this problem by presenting new classes of compounds that are useful in modulating SCD activity and regulating lipid levels, especially plasma lipid levels, and which are useful in the treatment of SCD-mediated diseases such as diseases related to dyslipktemia and disorders of lipid metabolism, especially diseases related to elevated lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome and the like. Related Literature PCT Published Patent Application WO 01 ^96327 discloses novel benzamide derivative compounds. PCT Published Patent Aop&caiions. WO 03/075929, WO 03/076400 and WO 03/076401, disclose compounds having histone deacetylase inhibiting enzymatic activity. BRIEF SUMMARY OF THE INVENTION The present invention provides pyntine 3ervatn« that modulate the activity of stearoyJ-CoA desaturase. Methods of usng sue? oerrvafc«s to modulate the activity of stearoyl-CoA desaturase and pharmaceutical zamacs&ans comprising such derivatives are also encompassed Accordingly, in one aspect, the inventor provides methods of inhibiting human stearoyl-CoA desaturase (hSCD) activity comprising contacting a source of hSCD with a compound of formula (I): ■ * * * wherein: x and y are each independently 1, 2 or 3: W is -0-, -N(R1)-, -C(OK -S(0)r; (where t is 0. 1 or 2), -N(R1)S(0)2-, -S(0)2N(R1)-, -OS(0)2N(R1)-, -C(0)N(R1K -OCr -C(S)N(R1h -0C(S)N(R1)-, -N(R1)C(0)- or -N(R1)C(0)N(R1}-; V is -C(O)-, -C(S)-, -CCOJNCR'K -C{0)0-. -S(0)2-. -S(0)2N(R1)- or -C(R11)H-; each R1 is independently selected from the group consisting of hydrogen, d-C^alkyl, C2-C12hydroxyalkyl, C-C12cycloalcytalcyl and C7-Ci9aralkyl; R2 is selected from the group consisting of Cr-Ci2alkyit C^C^alkenyl, C2-C12hydroxyaIkyl, C2-C12hydroxyalkenyi, Cs-C-pakoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, Cx-C12heterocyctyl, C3-C12heterocyclylalkyl, CrC^heteroaryl, and C3-C12heteroarylalkyl; or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl and where some or all of the rings may be fused to each other; x and y are each independently 1. 2 or 3; R1 is selected from the group consisting of hydrogen. C-rC^alkyl, C2-Ci2hydroxyalkyl, C4-Ci2cycloalkytalkyi and C-Coaralkyt: R2 is selected from the group consisting o? C7-C-?aIkyi. C3-C12alkenyl, C7-Ci2hydroxyalkyl, Ci-C^lkoxy, Cz-C2a!fcaxyacyi Cr-C-2Tydroxyalkenyl, Cs-C^cycloalkyl, C4-Ci2cydoaftcytallcy1T C-rC-»aralryt. C-C-rheteroaryl, C3-Ci2heterocyclylalkyl and Cr-C^heteroarytaky: Drovbec that R* is not pyrazinyl, pyridinonyl, pyrrolidinone or trrwdazotyi or R2 is a mufti-ring structure having 2ti Tngs wherein the rings are independently selected from the group consssng df cyaoakyi. heterocyclyl, aryl and heteroaryl, where some or ail of the rings may oe fusee ID each other R3 is selected from the group consstng of d-C-^aicyt. Cr-C12alkenyl, C3-Ci2hydroxyalkyl, Cy-C^hydroxyalkenyL Cr-C-jafcoxy. Cr-C-2aIkoxyaIkyl, C3-C12cycloalkyt, C4-Ci2cydoaIkylalkyt, aryl. C—C-^arafcyt. Cr-C^heterocyclyl, C3-Ci2heterocyclylalkylt Ci-Ci2heteroaryl and Cr-Czheteroaryialkyl; R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or-N(R'3}2; R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or d-Csalkyl; or R9and R9a together, or R10 and R10a together form an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9, R10, and R10a are each independently selected from hydrogen or CrC3allcyl; or one of R7, R7a, R10 and R10at together with one of Rs, R83, R9 and R9a, form an alkylene bridge, while the remaining R10, R,Q. R\ R7a. Re. R8, R9, and R9a are each independently selected from hydrogen or Cr-Q^alkyt; and each R13 is independently selected from hydrogen or d-CgalkylJ a stereoisomer, enantiomer or tautomer thereof, a pharmaceutical^ acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof. In another aspect, the invention provides compounds of formula (I) having the following formula (lib): administering to the mammal in need thereof a therapeutically effective amount of a compound of the invention as set forth above In another aspect, the invention provides compounds or pharmaceutical compositions useful in treating, preventing and'or diagnosing a disease or condition relating to SCD biological activity such as the diseases encompassed by cardiovascular disorders and/or metabolic syndrome rmciuding dysiipidemia, insulin resistance and obesity). In another aspect the invention provides meCxxis of preventing or treating a disease or condition related to elevated Epid tevcs suer as Dtasrra 6pd levels, especially elevated triglyceride or chotestero ievete r a patera afflicted with such elevated levels, comprising administering to sati pabert a therapeutically or prophylactically effective amount of a compositor as cfcctosed herein. The present invention also relates to novel compounds having therapeutic abSty to reduce lipid levels in an animal, especially triglyceride and choiesteroi tevete. In another aspect, the invention provides pharmaceutical compositions comprising the compounds of the invention as set forth above, and pharmaceutically acceptable excipients. In one embodiment, the present invention relates to a pharmaceutical composition comprising a compound of the invention in a pharmaceutically acceptable carrier and in an amount effective to modulate triglyceride level, or to treat diseases related to dysiipidemia and disorders of lipid metabolism, when administered to an animal, preferably a mammal, most preferably a human patient. In an embodiment of such composition, the patient has an elevated lipid level, such as elevated plasma triglycerides or cholesterol before administration of said compound and said compound is present in an amount effective to reduce said lipid level. In another aspect, the invention provides methods for treating a patient for, or protecting a patient from developing, a disease or condition mediated by stearoyl-CoA desaturase (SCD), which methods comprise administering to a patient afflicted with such disease or condition, or at risk of developing such disease or condition, a therapeutically effective amount of a compound that rtitoits activity of SCD in a patient when administered thereto. In another aspect, the invention provides methods for treating a range of diseases involving lipid metabolism utilizing compounds identified by the methods disclosed herein. In accordance therewith, there is disclosed herein a range of compounds having said activity, based on a screening assay for identifying, from a library of test compounds, a therapeutic agent which modulates the biological activity of said SCD and is useful in treating a human disorder or condition relating to serum levels of lipids, such as triglycerides, VLDL, HDL. LDu and/or total cholesterol. DETAILED DESCRPTION OF THE INVENTION Definitions As used in the specification and appended csarrs unless specified to the contrary, the following terms have the meaning nn1r w r~ Certain chemical groups named herein a-e zrocedec t* a shorthand notation indicating the total number of carton atoms that ar» t be kxrta r the indicated chemical group. For example; Cr-C-jafkyl describes an afty group, as defined below, having a total of 7 to 12 carbon atoms, and C Accordingly, as used in the specification and appended claims, unless specified to the contrary, the following terms have the meaning indicated: "Methoxy" refers to the -OCH3 radical. "Cyano" refers to the -CN radical. "Nitro" refers to the -N02 radical. "Trifluoromethyr refers to the -CF3 radical. "Oxo" refers to the =0 substituent Thioxo" refers to the =S substituenL "Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containrnj no unsaturation, having from one to twelve carbon atoms, preferably one to eight carbon atoms or one to six carbon atoms, and which is attached to the rest of the motecule by a single bond, e.g., methyl, ethyl, n-propyl, 1-methylethyl (/so-propyl), n-butyl, n-pentyl 1.1-dimethytethyI (f-butyl), and the like. Unless stated otherwise specifically in the specification, an alkyl group may be optionally substituted by one of the following groups: alkyt, akenyi, halo, haloalkenyl, cyano, nitro, aryl, cyctoalkyi heterocyclyL heteroaryl, -OR14, -OC(0)-R14, -N(R14)2, -C(0)R14, -C(0)OR14, -C(0)N(R14)2) -N(R14>C(0)OR16, -N(R14)C(0)R16, -N(R14)(S(0)tR16) (where t is 1 to 2), -S(0)tOR16 (where t is 1 to 2), -S(0)tR16 (where t is 0 to 2), and -S(0)tN(R14)2 (where t is 1 to 2) where each R14 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycioalkylalkyl, aryl (optionaily substituted with one or more halo groups), aralkyl, heterocyclyl, heterocytyialkyl, heteroaryl or heteroarylalkyl; and each R16 is alkyl, haloalkyl, cycloalkyi. cydoalkytaifcyi. ay. aralkyl. heterocyclyl, heterocytylalkyl, heteroaryl or heteroarytaftcyi. and where each of the above substituents is unsubstrtuted unless otherwise indicated nCi-C3alkyln refers to an alkyl radical as defined above containing one to three carbon atoms. The C-rC3alkyi radical may be opbona&y substituted as defined for an alkyl group. Xi-CealkyT refers to an aBcyt radical as definec aoove containing one to six carbon atoms. The Ci-CeaJkyI radical may be opeonai* subsfc&aed as defined for an alkyl group. "C^-CnzalkyT refers to an afcyi radical as aefoetf above containing one to twelve carbon atoms. The d-Cijalkyi radical may oc actanaK substituted as defined for an alkyl group. "C2-C6alkyl" refers to an alkyl radical as defriec above containing two to six carbon atoms. The C^Cealkyl radical may be opfonafty substituted as defined for an alkyl group. "C3-C6alkyT refers to an alkyl radical as defined above containing three to six carbon atoms. The C3-C6alkyl radical may be optionally substituted as defined for an alkyl group. "C3-C12alkyr refers to an alkyl radical as defined above containing three to twelve carbon atoms. The C3-Ci2alkyl radical may be optionally substituted as defined for an alkyl group. "Ce-C^alkyl" refers to an alkyl radical as defined above containing six to twelve carbon atoms. The C6-Ci2alkyl radical may be opfonaly substituted as defined for an alkyl group. "Cy-C^alky!" refers to an alkyl radical as defined above containing seven to twelve carbon atoms. The C7-C12alkyl radical may be optionally substituted as defined for an alkyl group. "Alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, contarwng at feast one double bond, having from two to twelve carbon atoms, preferably one to eight carbon atoms and which is attached to the rest of the molecule by a single bond, e.g., ethenyl, prop-1-enyl, but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the Bee. Unless stated otherwise specifically in the specification, an alkenyi group may be optionally substituted by one of the following groups: alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, -OR14, -OC(0)-R14, -N(R14)2, -C(0)R1\ -C(0)OR14, -C(0)N(R14)2, -N(R14)C(0)0R1S, -N(R14)C(0)R16, -N(R,4)(S(0>:R*i twnere t is I to 2), -S(0)tOR16 (where t is 1 to 2), -S(0)tR1$ (where t is 0 to 2). and -& Opfi(R^h iwhere t is 1 to 2) where each R14 is independently hydrogen, alkyl, hatoafcyi. cydoalkyl, cycloalkylalkyl, aryl, aralkyi, heterocyclyl, heterocyfytattcyt, heteroary or ^eteroarytaikyl; and each R16 is alkyl, haloalkyl, cydoalkyl, cyctoafkytaflcyi, aryl, arakyi heterocydyi. heterocyclylalkyl, heteroary! or heteroarylalkyl, and where each of the abwe substtuents is unsubstituted. "C3-C12alkenyT refers to an afcenyt ra&cai as defined aoove containing three to 12 carbon atoms. The Cr-Ci^^eny! radical may oe jcftcrtaK substituted as defined for an alkenyl group. "C2-C12alkenyT refers to an akenyt racfca as aenned above containing two to 12 carbon atoms. The C2-C12alkenyl radical may be ocnonatf substituted as defined above for an alkenyl group. "Alkyiene" and "alkyiene chain" refer to a strawft: or branched divalent hydrocarbon chain, linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturate and having from one to twelve carbon atoms, preferably having from one to eight carbons, e.g., methylene, ethylene, propylene, n-butylene, and the like. The alkyiene chain may be attached to the rest of the molecule and to the radical group through one carbon within the chain or through any two carbons within the chain. "Alkenylene" and "alkenylene chain" refer to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one doidDie bond and having from two to twelve carbon atoms, e.g., ethenylene, propenytene. r?-bufcenytene, and the like. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a double bond or a single bond. The points of attachment of the alkenylene chain to the rest of the motecute and to the radical group can be through one carbon or any two carbons within the chain. "Alkyiene bridge" refers to a straight or branched divalent hydrocarbon bridge, linking two different carbons of the same ring structure, consisting solely of carbon and hydrogen, containing no unsaturation and having from one to twelve carbon atoms, preferably having from one to eight carbons, e.g., methylene, ethylene, propylene, n-butylene, and the like. The alkyiene bridge may fink any two carbons within the ring structure. "Alkoxy" refers to a radical of the formula -ORa where Ra is an alkyl radical as defined above. The alkyl part of the alkoxy radical may be optionally substituted as defined above for an alkyl radical. "Ci-C6alkoxy" refers to an atkoxy radical as defined above containing one to six carbon atoms. The alkyl part of the C-Csa!koxy radical may be optionally substituted as defined above for an alkyl group. "d-C^alkoxy" refers to an afcoxy radical as defined above containing one to twelve carbon atoms. The alkyl part of the Ct-C-?afccxy 'aiScai may be optionally substituted as defined above for an afcyf group "Cr-C^lkoxy" refers to an akoxy radical as aennec above containing three to twelve carbon atoms. The alkyl part of the Cr-C-rahrav radical "nay be optionally substituted as defined above for an aicyi group. "AlkoxyalkyT refers to a radical of the formes -R^-O-Ra wrfiere each Ra is independently an alkyl radical as defined above The cancer atom may be bonded to any carbon in either alkyl radical. Each afcyl part of the aJkoxyaJkyf radical may be optionally substituted as defined above for an aflcyi group. wC2-Ci2alkoxyalkyr refers to an alkoxyalkyi radical as defined above containing two to twelve carbon atoms. Each alkyl part of the Cj-C-rakoxyalkyl radical may be optionally substituted as defined above for an alkyl group. "C3alkoxyalkyr refers to an alkoxyalkyi radical as defined above containing three carbon atoms. Each alkyl part of the C3alkoxyalkyl radical may be optionally substituted as defined above for an alkyl group. "C3-Ci2alkoxyalkyr refers to an alkoxyalkyi radical as defined above containing three to twelve carbon atoms. Each alkyl part of the Cr-C-^aBcoxyalkyl radical may be optionally substituted as defined above for an alkyl group. "Alkylsulfonyl" refers to a radical of the formula -^O^Ra where Ra is an alkyl group as defined above. The alkyl part of the alkylsulfonyl radical may be optionally substituted as defined above for an alkyl group. MCi-C6alkyIsulfonyr refers to an alkyisutfonyf radical as defined above having one to six carbon atoms. The Ci-Cealkybulfonyl group may be optionally substituted as defined above for an alkylsulfonyl group. "Aryl" refers to aromatic monocyclic or multicycle hydrocarbon ring system consisting only of hydrogen and carbon and containing from 6 to 19 carbon atoms, preferably 6 to 10 carbon atoms, where the ring system may be partially or fully saturated. Aryl groups include, but are not limited to groups such as fluorenyl, phenyl and naphthyl. Unless stated otherwise specifically in the specification, the term "aryl" or the prefix "ar-" (such as in "aralkyl") is meant to include aryl radicals optionally substituted by one or more substrtuents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyi. cyano. nitro. aryi aralkyi. cyctoalkyl. cycloalkyialkyi, heterocyclyl, heterocyclytalkyt, heteroaryt. beteroarytalkyl, -R15-OR14, -R^-OCODH14, -R15-N(R14)2, -R15-C(0)R14. -R15-C(0)OR14. -R£-C(0)N(R14)2, -Rl5-N(R14)C(0)OR16, -R15-N(R14)C(0)R16, -R15-N(R"4>fS (where t is 1 to 2), -R15-S(0)tOR16 (where t is 1 to 2), -R15-S(0)rR16 (where :S3ID 2). and -R15-S(0)tN(R14)2 (where t is 1 to 2) where each R'* is nbependenSy hydrogen, alkyl, haloalkyi, cycloalkyl, cycloalkyialkyi, aryi. aralkyi, heterocycJyL neterocyctylalkyl, heteroaryl or heteroarylalkyt: each R£ is ndependentv a 3rec: bond or a straight or branched alkytene or alkenyiene chain, and each ~~ s afcyi u,aioalcy(, cydoalkyl, cycloalkyialkyi, aryi, aralkyi, heterocyctyi, heterocyoytairy1 neteroaryi or heteroarylalkylt and where each of the above substitiente is jnsubsttuted. "Aralkyl" refers to a radical of the formula -R#Re »r>ere R^san alkyl radical as defined above and Rb is one or more aryi radicab as defined above, e.g., benzyl, diphenylmethyl and the like. The aryi part of the araicy racScal may be optionally substituted as described above for an aryi group. The afcyi part of the aralkyi radical may be optionally substituted as defined above for an alcyl group. "Cr-C^aralkyl" refers to an aralkyi group as defied above containing seven to twelve carbon atoms. The aryi part of the C7-C12aralkyl radical may be optionally substituted as described above for an aryi group. The alkyl part of the Cr-C^aralkyl radical may be optionally substituted as defined above for an alkyl group. "C7-C19aralkyr refers to an aralkyi group as defkied above containing seven to nineteen carbon atoms. The aryi part of the C7-C-.oaraicyl radical may be optionally substituted as described above for an aryi group. The aflcyl part of the Cy-C^aralkyl radical may be optionally substituted as defined above for an alkyl group. "Ci3-C19aralkyr refers to an aralkyi group as defined above containing thirteen to nineteen carbon atoms. The aryi part of the C:r-C79araBcyl radical may be optionally substituted as described above for an aryi group. The afeyl part of the C13-C19aralkyl radical may be optionally substituted as defined above for an alcyl group. "Aralkenyl" refers to a radical of the formula -RcR« where Re is an alkenyl radical as defined above and Rb is one or more aryi radicab as defined above, which may be optionally substituted as described above. The aryi part of the aralkenyl radical may be optionally substituted as described above for an aryi group. The alkenyl part of the aralkenyl radical may be optionally substituted as defined above for an alkenyl group. "Aryloxy" refers to a radical of the formula -ORb where Rb is an aryi group as defined above. The aryi part of the aryloxy radical may be optionally substituted as defined above. "Aryl-d-Cealkyl" refers to a radical of the for-nuia -R.-R where Rh is an unbranched alkyl radical having one to six carbons and R is an aryf group attached to the terminal carbon of the alkyl radical. "CycloalkyT refers to a stable norvaromatic monocycfc or bicyciic hydrocarbon radical consisting solely of carbon and hydrogen atoms havmg from three to fifteen carbon atoms, preferably having from three to twelve cartor atoms and which is saturated or unsaturated and attached to the rest c* the p-oiecuie by a single bond, e.g., cyclopropyl, cyctobutyi, cyctoperrtyl cydoheary oecmrrrf and the Bee. Unless otherwise stated specifically in the specification the terr "rycicafcy 5 meant to include cycloalkyl radicals which are opbonafty subs&ued ny one or more substituents selected from the group consisting of alkyl. afcery. ftaic raicaicy. haioalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloaftcyialkyl. beterocycV "eterocycytalky1, heteroaryl, heteroarylalkyl, -R15-OR14, -R15-OC(0>-R14, -R1£-N(R~}- -R£-C/0>R'4, -R15-C(0)OR14, -R15-C(0)N(R14)2, -R15-N(R14)C(0)OR16, -R15-N(R")C/0)RT -R--N(R14)(S(0)tR16) (where t is 1 to 2), -R15-S(0)tOR16 (where t is 1 to 2), -R^-StOrR16 (where t is 0 to 2), and -R15-S(0)tN(R14)2 (where t is 1 to 2) where each R"4 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryi, aralkyl heterocydyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; each R15 is independently a direct bond or a straight or branched alkylene or alkenylene chain; and each R16 is alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl, and where each of the above substituents is unsubstituted. "C3-C6cycloalkyr refers to a cycloalkyl radical as defined above having three to six carbon atoms. The C3-C6cycloalkyl radical may be optionaRy substituted as defined above for a cycloalkyl group. "C3-C12cycIoaIkyl" refers to a cycloalkyl radical as defined above having three to twelve carbon atoms. The C3-C12cycloalkyl radical may be optionally substituted as defined above for a cycloalkyl group. "Cycloalkylalkyl" refers to a radical of the forcmia -RaRc where Ra is an alkyl radical as defined above and Rd is a cycloalkyl radical as defined above. The cycloalkyl part of the cycloalkyl radical may be optionaBy substituted as defined above for a cycloalkyl radical. The alkyl part of the cycloalkyl radical may be optionally substituted as defined above for an alkyl radical. "C4-C12cycloaIkylalkyr refers to a cycloalkylalkyl radical as defined above having four to twelve carbon atoms. The C4-C12cyctoalkylalkyl radical may be optionally substituted as defined above for a cycloalkylalkyl group. "Halo" refers to bromo, chloro, fluoro or iodo. "Haloalkyl" refers to an alkyl radical, as defined above, that rs substituted by one or more halo radicals, as defined above, e.g.. triftxrometfryt. difluorornethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyt-2-fkioroethyt. 3-bromo-2-fluoropropyl, 1-bromomethyi-2-bromoethy* and the fike The alkyl part of the haloalkyl radical may be optionally substituted as defined above for an alkyl group. "Haloalkenyl" refers to an alkenyl radical, as defined above that is substituted by one or more halo radicals, as defined above, e.g 2-srorroethenyi, 3-bromoprop-1-enyl, and the like. The alkenyl part of the haioakery jLaoa n^ay se optionally substituted as defined above for an akyl group "HeterocyclyT refers to a stable 3- to 1S-memoerec nor-aromafcc ring radical which consists of carbon atoms and from one to five "weroafcrns selected from the group consisting of nitrogen, oxygen and sulfur. For purposes of this invention, the heterocyctyl radical may be a monocyclic, bicycfc. tricycic ortetracycfic ring system, which may include fused or bridged ring systems: and the nitrogen, carbon or sulfur atoms in the heterocyclyl radical may be optionally oxkfeed; the nitrogen atom may be optionally quaternized; and the heterocyclyl radical may be partially or fully saturated. Examples of such heterocyclyl radicals include, but are not limited to, dioxolanyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyi, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyi, 2-oxopiperidinyl, 2-oxopyrroIidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1dioxo-tHomorpho&TyI. Unless stated otherwise specifically in the specification, the term "heterocydyT is meant to include heterocyclyl radicals as defined above which are optbraly substiuted by one or more substituents selected from the group consisting of akyt alkenyl, hato, haloalkyl, haloalkenyl, cyano, oxo, thioxo, nitro, aryl, aralkyi, cydoaflcyl, cycloalkylalkyi, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalcyt. -R15-OR~, -R15-OC(0)-R14, -R15-N(R14)2, -R15-C(0)R14, -R15-C(0)OR14, -R15-C{0)N(R1)2, -R15-N(R14)C(0)OR16, -R15-N(R14)C(0)R16, -R15-N(R14)(S(0)tR16) (where t is 1 to 2). -R15-S(0)t0R16 (where t is 1 to 2), -R15-S(0)tR16 (where t is 0 to 2), and -R15-S(0)N(R14>2 (where t is 1 to 2) where each R14 is independently hydrogen, alkyl, alkenyl, hatoaicyi, cycloalkyi, cycloalkylalkyi, aryl, aralkyi, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; each R15 is independently a direct bond or a straight or branched afkytene or alkenytene chain; and each R16 is alkyl, alkenyl, haloalkyl, cycloalkyi, cycloalkytalkyl, aryl, aralkyi, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl, and where each of the above substituents is unsubstituted. "C3-C12heterocycty!" refers to a heterocyctyi radical as defined above having three to twelve carbons. The C3-C-2heterocycty1 may be optona&y substituted as defined above for a heterocyctyl group. "HeterocyctylalkyH refers to a radical of the forrouta -R»R« where Ra is an alkyl radical as defined above and Re is a helerocydyi racfica? as defined above, and if the heterocyctyl is a nitrogen-containing heterocydyl the beterocycty! may be attached to the alkyl radical at the nitrogen atom. The afkyi part of tn heterocycyaIkyi radical may be optionally substituted as defined above for an air/ jnxc ^"he heterocyctyl part of the heterocyctytalkyl radical may be opfooaK sjfcsbfcjled as defined above for a heterocyctyl group. "C3-C12heterocycfytalkyr refers to a heteroc^MaHry raeScai as defined above having three to twelve carbons. The C3-C^?heterocyciytairy "Heteroaryl" refers to a 5- to 18-membered aromatic mg radical which consists of carbon atoms and from one to five heteroatoms setected from the group consisting of nitrogen, oxygen and sulfur. For purposes of this invention, the heteroaryl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused or bridged ring systems; and the nitrogen, carbon or sulfur atoms in the heteroaryl radical may be optionally oxidized; the nitrogen atom may be optionally quatemized. Examples include, but are not limited to, azeptnyl, acridinyl, benzimidazolyl, benzthiazolyl, benzindolyl, benzothiadiazolyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl. benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothaophenyf), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl. tinnoTinyi. cSbenzofuranyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indolyi, indazolyl, tsoindoJyt indofinyt, isoindolinyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazofyl, 2-oxoazepinyi, oxazolyl, oxiranyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl pteridinyi, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, qurazofinyi quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, thiazoh/i, thiadiazxtfyL triazolyl. tetrazolyl, triazinyl, and thiophenyl. Unless stated otherwise specificafly in the specification, the term "heteroaryl" is meant to include heteroaryl radicate as defined above which are optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, oxo, thioxo, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyctyl, heterocyclytalkyl, heteroaryl, heteroarylalkyl, -R15-OR14, -R15-OC(0)-R14, -R15-N(R14)2, -R15-C(0)R14, -R15-C(0)OR14, -R15-C(0)N(R14)2) -R15-N(R14)C(0)OR16, -R15-N(R14)C(0)R16, -R15-N(R14)(S(0)tR16) (where t is 1 to 2), -R15-S(0)tOR16 (where t is 1 to 2). -R "-S-O'MR16 (where t is 0 to 2), and -R15-S(0)tN(R14)2 (where t is 1 to 2) where each R'* is rKJependentty hydrogen, alkyl, alkenyl, hatoalkyl, cycloalkyl, cycloalkytalkyl aryl araikyt. heterocyclyl, heterocyctylalkyt, heteroaryl or heteroarytalkyt: each R"£ rs >dependentty a direct bond or a straight or branched alkytene or akenytene char and eac* R,s is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryf. aralkyi. heterocycsy! ^eterocydytalkyl. heteroaryl or heteroarylalkyl, and where each of the above substrtuents is unsubstituted. "Ci-Ci2heteroaryT refers to a heteroaryl radcat as aefinec above having one to twelve carbon atoms. The Ci-C12beteroary* group may oe opbonafty substituted as defined above for a heteroaryl group "Cs-C^heteroaryT refers to a heteroaryl racfcal as aeftned above having five to twelve carbon atoms. The Cs-C^heteroaryl group may be op6ona»y substituted as defined above for a heteroaryl group. "Heteroarylalkyl" refers to a radical of the formula -R^R* where Ra is an alkyl radical as defined above and Rf is a heteroaryl radical as defined above. The heteroaryl part of the heteroarylalkyl radical may be optionally substituted as defined above for a heteroaryl group. The alkyl part of the heteroarylalkyl radical may be optionally substituted as defined above for an alkyl group. "C3-Ci2heteroarylalkyl" refers to a heteroarylalkyl radical as defined above having three to twelve carbon atoms. The Cr-C^heteroarytalkyl group may be optionally substituted as defined above for a heteroarytafcy* group. "Heteroarylcycloalkyl" refers to a radical of the formula -R^Rr where Rd is a cycloalkyl radical as defined above and Rf is a heteroaryl radical as defined above. The cycloalkyl part of the heteroarylcycloalkyl radical may be optionally substituted as defined above for a cycloalkyl group. The heteroaryl part of the heteroarylcycloalkyl radical may be optionally substituted as defined above for a heteroaryl group. "Heteroarylalkenyl" refers to a radical of the formula -RoR* where Rb is an alkenyl radical as defined above and Rf is a heteroaryl racfcal as defined above. The heteroaryl part of the heteroarylalkenyl radical may be optionally substituted as defined above for a heteroaryl group. The alkenyl part of the heteroarylalkenyl radical may be optionally substituted as defined above for an alkenyl group. "Hydroxyalkyl" refers to a radical of the formula -R.-OH where Ra is an alkyl radical as defined above. The hydroxy group may be attached to the alkyl radical on any carbon within the alkyl radical. The alkyl part of the hydroxyalkyl group may be optionally substituted as defined above for an alkyl group. "C2-C12hydroxyalkyr refers to a hydroxyalkyf radical as defined above containing two to twelve carbon atoms. The atkyt part of the Cr-C-2hydroxyaIkyl radical may be optionally substituted as defined above for an alky! group nC;rC12hydroxyaIkyr refers to a hydroxyalkyf racScaf as defined above containing three to twelve carbon atoms. The alkyl part erf the Cr-C-;>hydroxyaIkyl radical may be optionally substituted as defined above for ar akyi group "Cr-Ci2hydroxyaIkyr refers to a hydroxyafkyf radca as Defined above containing seven to twelve carbon atoms The alky* parr of the C-C-y^ydroxyalkyl radical may be optionally substituted as defined above tor ar a&ry grouo "HydroxyalkenyT refers to a radical of the formula -L-OH vwhere R^ is an alkenyl radical as defined above. The hydroxy group may x aGached to the alkenyl radical on any carbon within the alkenyl radicaL The akeny sar: zf the hydroxyalkenyl group may be optionally substituted as defined above far ar altenyt group. MC2-Ci2hydroxyalkenyT refers to a hydroxyalcenyf radicai as defined above containing two to twelve carbon atoms. The alkenyl pat of the Cr-C-^hydroxyalkenyl radical may be optionally substituted as defined above for an akenyl group. "C3-C12hydroxyalkenyr refers to an hydroxyalkenyl radical as defined above containing three to twelve carbon atoms. The alkenyl part of the C3-C12hydroxyalkenyl radical may be optionally substituted as defined above for an alkenyl group. "Hydroxyl-d-Ce-alkyl" refers to a radical of the formula -Rh-OH where Rh is an unbranched alkyl radical having one to six carbons and the hydroxy radical is attached to the terminal carbon. "Trihaloalkyl" refers to an alkyl radical, as defined above, that is substituted by three halo radicals, as defined above, e.g., trifluoromethyl The akyl part of the trihaloalkyl radical may be optionally substituted as defined above for an alkyl group. "Ci-Cgtrihaloalkyr refers to a trihaloalkyl radicai as defined above having one to six carbon atoms. The CTCetrihaloalkyl may be optionaiy substituted as defined above for a trihaloalkyl group. "Trihaloalkoxy" refers to a radical of the formula -OR^ where R^ is a trihaloalkyl group as defined above. The trihaloalkyl part of the trihatoakoxy group may be optionally substituted as defined above for a trihaloalkyl group. "C^Cetrihaloalkoxy" refers to a trihatoakoxy radical as defined above having one to six carbon atoms. The Ci-C6trihatoalkoxy group may be optionally substituted as defined above for a trihaloalkoxy group. "A multi-ring structure" refers to a multicyclic ring system comprised of two to four rings wherein the rings are independently selected from cycloalkyl, aryl, heterocyclyl or heteroaryl as defined above. Each cyctoaflcy* may be optionally substituted as defined above for a cyctoattcyt group. Each ary\ may be optionally substituted as defined above for an aryl group. Each heterocydyi may be optionally substituted as defined above for a heterocydyl group Eacfc heteroaryl may be optionally substituted as defined above for a hefceroary* group The nngs may be attached to other through direct bonds or some or afl ctf the nngs may be fused to each other. Examples include, but are not fcmited to a cyctoaiky -adca! substituted by aryl group; a cydoalkyl group substituted by an aryl group **ct. r tun ES substituted by another aryl group; and so forth. "Prodrugs" is meant to indicate a compound fat mav be converted under physiological conditions or by sofvotysis to a biotogcaiy ac&ve corcound c^ the invention. Thus, the term "prodrug" refers to a mefcaboic crecxrscr of a compound of the invention that is pharmaceutical^ acceptable. A prodrug may be inactive when administered to a subject in need thereof, but is converted r? nvc to an active compound of the invention. Prodrugs are typically rapidly transformed r. vrvo to yield the parent compound of the invention, for example, by hydrolysis in blood. The prodrug compound often offers advantages of solubility, tissue compatibility or deteyed release in a mammalian organism (see, Bundgard, H., Design of Prodrugs (1985), pp. 7-9, 21-24 (Elsevier, Amsterdam). A discussion of prodrugs is provided in Higuchi, T.f et ai, "Pro-drugs as Novel Delivery Systems," A.C.S. Symposium Series, Vol. 14, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated r. fui by reference herein. The term "prodrug" is also meant to include any covatentiy bonded carriers which release the active compound of the invention in vivo when such prodrug is administered to a mammalian subject. Prodrugs of a compound of the invention may be prepared by modifying functional groups present in the compound of the invention in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound of the invention. Prodrugs include compounds of the invention wherein a hydroxy, amino or mercapto group is bonded to any group that when the prodrug of the compound of the invention is administered to a mammalian subject cleaves to form a free hydroxy, free amino or free mercapto group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol or amine functional groups in the compounds of the invention and the Bee. "Stable compound" and "stable structure" are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent. "Mammal" includes humans and domestic anrnais. such as cats, dogs, swine, cattle, sheep, goats, horses, rabbits, and the fike. "Optional" or "optionally" means that the subsequently described event of circumstances may or may not occur, and that the description nciudes ^stances where said event or circumstance occurs and instances in which t aoes not For example, "optionally substituted aryT means that the aryl racficai may or may not be substituted and that the description includes both substituted ary racScae anc ar/ rackets having no substitution. "Pharmaceutical^ acceptable carrier, diuent or eaeperT" roudes without limitation any adjuvant carrier, excipient gfctant, sweetener; agerc Ajem preservative, dye/colorant, flavor enhancer, surfactant vetting agent tfepersng agent suspending agent, stabilizer, isotonic agent solvent or emutsifier whicfc has been approved by the United States Food and Drug Administration as being acceptable for use m humans or domestic animals. Tharmaceutically acceptable salt" includes both aad and base addition salts. "Pharmaceutical^ acceptable acid addition safT refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as, but not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric add, phosphoric acid and the like, and organic acids such as, but not limited to, acetic acid, 2.2-dichtoroacetic acid, adipic acid, alginic acid, ascorbic acid, asparfcc acid, benzenesutfbnic acid, benzoic acid, 4-acetamidobenzoic acid, camphoric acid, campboMO-suKonic acid, capric acid, caproic acid, capryiic acid, carbonic acid, cinnamic acid, citric acid, eyjamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydrcKyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-giutaric add. glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic aod. lactobionic acid, taunc acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesutfomc acid, muac acid, naphthalene-1,5-disulfonic acid, naphthalene-2-suffonic acki 1-hydroxy-2~naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic add, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosaficyic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid, undecylenic acid, and the like. "Pharmaceutical acceptable base addition salt" refers to those salts which retain the biological effectiveness and properties of the free adds, which are not biologically or otherwise undesirable. These salts are prepared from addition of an riorganic base or an organic base to the free acid. Salts derived from inorganic bases indude. but are not limited to, the sodium, potassium, lithium, ammonium, cataum. magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Preferred inorganc sate are the ammonium, sodium, potassium, calcium, and magnesium safts Salts derived from organic bases include, but are not limited to, salts of primary secondary and tertiary amines, substituted amines including naturafry occurring suDstiuted arranes, cyclic amines and basic ion exchange resins, such as ammona. soproc^arwie trimethytamine, diethyiamine, triethytamne, tnpropytamne ctetTaraarnre ethanolamine, deanol, 2^inr>ethytam!noethanot. 2-yidi'M«JrfhanaL dicyclohexylamine, lysine, arg'mine, histkSne. caffeine, procane ^yarataamrje, choline, betaine, benethamine, benzathine, ethylenediarTMne. gfcjcosarnne mehyglucamine, theobromine, triethanolamine, tromethamine, purines, piperazsie. piperidine, A/-ethylpiperidine, polyamine resins and the Bee. Particularly preferred organic bases are isopropylamine, diethyiamine, ethanolamine, trimethytamine, cficydohexytamine, choline and caffeine. Often crystallizations produce a solvate of the compound of the invention. As used herein, the term "solvate" refers to an aggregate that comprises one or more molecules of a compound of the invention with one or more molecules of solvent. The solvent may be water, in which case the solvate may be a hydrate. Alternatively, the solvent may be an organic solvent. Thus, the compounds of the present invention may exist as a hydrate, including a monohydrate, dihydrate, hemihydrate. sesquihydrate, trihydrate, tetrahydrate and the like, as well as the corresporxing soJvated forms. The compound of the invention may be true solvates, wh&e in other cases, the compound of the invention may merely retain adventitious water or be a mixture of water plus some adventitious solvent. A "pharmaceutical composition" refers to a formuiabon of a compound of the invention and a medium generally accepted in the art for the de&very of the biologically active compound to mammals, e.g., humans. Such a mecSum includes all pharmaceutical^ acceptable carriers, diluents or excipients therefor. 'Therapeutically effective amount" refers to that amouit of a compound of the invention which, when administered to a mammal, preferably a human, is sufficient to effect treatment, as defined below, of an SCD-mediated disease or condition in the mammal, preferably a human. The amount of a compound of the invention which constitutes a 'therapeutically effective amount" will vary depending on the compound, the condition and its severity, and the age of the mammal to be treated, but can be determined routinely by one of ordinary skill in the art havng regard to hts own knowledge and to this disclosure. Treating" or 'treatment" as used herein covers the treatment of the disease or condition of interest in a mammal, preferably a human, having the dsease or disorder of interest, and includes: (i) preventing the disease or condition from occxrmg r a mammal, in particular, when such mammal is predisposed to the oxtSbor but has not yet been diagnosed as having it; (ii) inhibiting the disease or concfiforv i.e.. diiesj^ te devetaoment or (iii) relieving the disease or coocSton. i e , causrxj 'tayessm of the disease or condition. As used herein, the terms "disease" and "concfibor" may oe used interchangeably or may be different in that the particular naiady or concfltion may not have a known causative agent (so that ebotogy has not yet been worked out) and it is therefore not yet recognized as a disease but onfy as an tirxtesirabte condition or syndrome, wherein a more or less specific set of symptoms have been identified by clinicians. The compounds of the invention, or their pharmaceutical^ acceptable salts may contain one or more asymmetric centers and may thus give rise to enantiomers, diastereomers, and other stereoisomers forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)- or, as (D>- or (L>- for amino acids. The present invention is meant to include all such possible isomers, as weB as their racemic and optically pure forms. Optically active (+) and {-;. (Ry and (Sy, or (D)- and (L)- isomers may be prepared using chiral synthons or dhiral reagents, or resolved using conventional techniques, such as HPLC using a chiral coJumn. When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it ts intended that the compounds include both E and Z geometric isomers. Likewise, aD tautomeric forms are also intended to be included. A "stereoisomer" refers to a compound made up of the same atoms bonded by the same bonds but having different three-dimensional structures, which are not interchangeable. The present invention contemplates various stereoisomers and mixtures thereof and includes "enantiomers", which refers to two stereoisomers whose molecules are nonsuperimposeable mirror images of one another. A "tautomer" refers to a proton shift from one atom of a molecule to another atom of the same molecule. The present invention includes tautomers of any said compounds. The chemical naming protocol and structure diagrams used herein employ and rely the chemical naming features as utilized by Chemdraw version 7.0.1 (available from Cambridgesoft Corp., Cambridge, MA). For complex chemicaJ names employed herein, a substituent group is named before the group to wnicr it attaches. For example, cyclopropylethyf comprises an ethyl backbone wit?" ryooorapy* substituent In chemical structure diagrams, all bonds are identified except for sorr>e carbon atoms which are assumed to be bonded to sufficient hydroger atoms tc corrpiese the valency. As an example, a compound of formula (V!b). as sef farsh above n the Summary of the Invention, wherein x and y are each 1. R* R- R5. =?* R~ R7a, RB, R83, R9, R9, R10and R10a are each hydrogen; R2 is 3^4-fhx>ropner>y>prDp^ and R3 is 2-trifluoromethyl phenyl, i.e., a compound of the fofcwing famia' is named herein as 5-[4-(2-Trifluoromethyi-ben2oyl)«piperazin-1-y!}-pyridine-2-carboxylic acid [3-(4-fIuoro-phenyl)-propyI}-amide. Certain radical groups of the compounds of the invention are depicted herein as linkages between two parts of the compounds of the inversion. For example, in the following formula (I):' W is described, for example, as being -C(0)N(R> or -N(R1)C(0)N(R')-; and V is described as -C(O)-. This description is meant to descrfoe a W group attached to the R2 group as follows: R2-C(0)N(R1)- or R2^N(R1)C(0)N(R1K and meant to describe a V group attached to the R3 group as follows; -C(0)R3. In other words, the description of the W and V linkage groups are meant to be read from left to right in view of formula (I) as depicted above. Embodiments of the Invention In one embodiment of the invention, compounds of formate (Da), as set forth above in the Summary of the Invention, are directed to compounds wherein x and y are each 1; R1 is hydrogen or d-Cealkyi; R2 is setected frorr the group consisting of In another embodiment of the invention, compounds of formula (lib), as set forth above in the Summary of the Invention, are directed to compounds wherein x and y are each 1; R1 is hydrogen or d-C6alkyl; R2is selected from the group consisting of d-Cealkyl, C2-d2aIkenyl, C2-Ci2hydroxyalkyl, CrC12hydroxyalkenyt, d-C6a!koxy, C3-C12alkoxyalkyl, C3-C12cycloalkyI, C4-C12cycloalkylalkylt d-dsaralkyl, C3-Ci2 heterocyclyl, C3-C12heterocyc!ylalkyl, d-Ci2heteroaryI and C3-C12heteroarylalkyl; R3 is phenyl optionally substituted by one or more substituents setected from the group consisting of halo, cyano, nitro, hydroxy, d-Ceaftyl d-Cetrioaioalkyl, d-Cetrihaloalkoxy, d-Cgalkylsulfonyl, -N(R12)2l -00(0^. -C{0)OR'2 and -S(0)2N(Rt2)2; R4, R5 and R6 are each hydrogen; R7, R7a. Ra. R8. RS. R5, R10, and R10a are each hydrogen; and each R12 is independently setected from hydrogen, d-C6alkyl, C3-dcycIoaIkyl, aryl oraralkyl. One embodiment of this embodiment are compounds wherein R2 is C7-C12aralkyl optionally substituted by one or more substituerts setected from the group consisting of halo, Ci-C3alkyl and d-Cetrihaloalkyt and R3 ts phenyl optionally substituted by one or more substituents setected from the group consisting of halo, d-Cealkyl, d-C6trihaloaIkyl and d-Cetrihatoa!koxy. Another embodiment of this embodiment are compounds wherein R2 is d-C12alkyl or C2-C12alkenyl; and R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, d-Cealkyl, d-C6trihaloalkyl and d-C6trihaIoalkoxy. Another embodiment of this embodiment are compounds wherein R2 is One embodiment of this embodiment are compounds wnerein R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-C6alkyi, Ci-Cstrihatoalkyl. C-Ctrihatoalkoxy, d-Ceaikylsulfonyl, -N(R12)2, -OC(0)R'2, -C(0)OR12. -S(OfcN(R2fc. cycioaikyt. heterocyclyl, heteroaryl and heteroarylcydoalkyt; and eacf^ n'2 rs ndependentty selected from hydrogen, d-Cealkyl, CrCsCydoaftcyl, aryl or arafcyi In another embodiment of the invention, compounds d formuia =V). as set forth above in the Summary of the Invention, are (Srected to corTpcxncs inhere" x and y are each 1; Wa is -N(R1)s Va ts -C(OK R' is hydrogen or C-Cta* ^s selected from the group consisting of C^-C^kyl CVd^lkenyt. Cr-dahydroavafcy. C2-C12hydroxyalkenyl1 Cr-dzalkoxyalkyl, Cr-drcyctoaic/ Ci-C-^cjcioakytakyl, aryl, C7-C19aralkyl, C3-C12 heterocyclyl, CrC^heterocydytaBcyl. C-C^neaaudiyl and C3-C12heteroarylalkyl; R3 is selected from the group consisting of C—C^afcyf, C2-Ci2alkenyl, Cr-C^hydroxyalkyl, Cs-C^hydroxyalkenyt, Cr-djakoxyakyl, C3-Ci2cycloalkyl, C4-C12cycloalkylalkyl, aryl, d-dsarafkyl, QrC12heteroc>^yl, C3-Ci2heterocyclylalkyl, C^C^heteroaryl and CrC^heteroarytakyt R4, R5 and R6 are each hydrogen; and R7, R7a, R8, R8a, R9, R98, R10, and R10a are each hydrogen. One embodiment of this embodiment are compounds wherein R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-dalkyl. Ci-C6trihaloalkyl, d-C6trihaIoalkoxy, d-Cealkylsulfonyl, -N(R12)2j -OC(0)R12, -C(0)OR12, -SfO^CR^fc, cycloalkyl, heterocyclyl, heteroaryl and heteroarylcycloalkyi; and each R2 is independently selected from hydrogen, Ci-C6alkyl, C3-C6cyctoalkyl, aryl or araicyt. In another embodiment of the invention, compounds of formula (V), as set forth above in the Summary of the Invention, are directed to compounds wherein x and y are each 1; Wa is -S(0)r (where t is 0,1 or 2); Va is -C(OK R2 is selected from the group consisting of d-C^alkyl, Ca-C^alkenyl, C2-d2hydroxyaicyi drdahydroxyalkenyl, C3-Ci2alkoxyalkyl, C3-C12cycloalkyl, C4-C12cyctoalkyta!kyi, aryl C-dgarakyl, C3-C12 heterocyclyl, C3-Ci2heterocyclylalkyl, d-C12heteroaryl and Cr-C-2heteroarytaIkyl; R3 is selected from the group consisting of d-d^kyl, C2-d2aBcenyt Cz-dzhydroxyalkyl, C2-d2hydroxyalkenyl, C2-C12alkoxyalkyl, Cr-djcydoalkyf, Cr-drcyctoalkytalkyl, aryl, C7-C19aralkyl, C3-Ci2heterocyclyl, C3-C12heterocyclytalkyl, d-d2heteroary! and C3-C12heteroarylalkyl; R4, R5 and R6 are each hydrogen; and R\ R7a, Re, R83, R9, R9a, R10, and R10a are each hydrogen. One embodiment of this embodiment are compounds wherein R3 is phenyl optionally substituted by one or more substituents selected from the group consisting Another embodiment of this embodiment are compounds wherein R2 is C3-Ci2cycloalkyl or C4-d2cycloalkylaIkyl; and R3 is phenyl optionaBy substituted by one or more substituents selected from the group consisting of hato. C--CsaDcy!. Ct-C6trihaloaIkyI and d-C6trihaloalkoxy. Another embodiment of this embodiment are compounds where** R~ ts C7-C12aralkyl optionally substituted by one or more substituents setected from the group consisting of halo, d-C3alky1 and Ci-C6trfoataaBcyit and ^ JS naphthyl optionally substituted by one or more substituents setected from the you^ conststng of hate, d-C6aIkyi, d~C6trihaloa!kyt and d-Cetrfoaloalkaxy Another embodiment of this embodiment are compounds #^^g,e^^' R* ts C3-d2heterocycfylalkyI optionally substituted by one or mar* suosd&jents setected from the group consisting of halo, cyano, nitro. hydroxy. C—daicyl C—Cstnhaloalkyl, d-Cetrihaloalkoxy, d-C6alkylsulfonyl, -N(Rt2)i, -OC(0)R'2. -OOOR2 or -S(0)2N(R12)2; R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C6a'kyl. d-C6trihak>alkyt and C-Cstrtialoalkoxy; and each R12 is independently selected from hydrogen, d-dafcy(. Cr-C$cycloalkyl, aryl or aralkyl. One embodiment of this embodiment are compounds wherein R2 is 2-piperazinylethyl optionally substituted by -C(0)OR12. Specific embodiments of the compounds of the invention are disclosed herein in the following Reaction Schemes and Examples. In another embodiment, the methods of the invention are directed to methods of treating a disease or condition mediated by stearoyJ-CoA desafcjrase (SCD) in a mammal, wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of formulae (lla). (lib), (III), (IV), (V), (Via) and (Vlb). In another embodiment of the pharmaceutical compositions of the invention are directed to pharmaceutical compositions comprising a pharmaceuticaiy acceptable excipient and a therapeutically effective amount of a compound of formuiae (ila), (lib), (III), (IV), (V), (Via) and (Vlb). In another embodiment, the methods of the invention are directed towards the treatment and/or prevention of diseases mediated by stearoyJ-CoA desaturase (SCD), especially human SCD (hSCD), preferably diseases related to dysfipkiemia and disorders of lipid metabolism, and especially a disease related to etevated plasma lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome and the like by administering an effective amount of a compound of the invention. The present invention also relates to pharmaceutical composition containing the compounds of the invention. In one embodiment, the inventor, relates to a composition comprising compounds of the invention in a pharmaceutical^ acceptable carrier and in an amount effective to modulate triglyceride tevei or to treat diseases related to dyslipidemia and disorders of lipid metabolism, wher administered to an animal, preferably a mammal, most preferably a human patoert In an embodiment of such composition, the patient has an elevated ipid level, sue- as elevated triglycerides or cholesterol, before administration of said compound of the r^grbon and the compound of the invention is present in an amount effective ID ~eauce sa£ iotd level. Utility and Testing of the Compounds of the Invention The present invention relates to compounds, pharmaceu&cal compassions and methods of using the compounds and pharmaceutical composibons for the treatment and/or prevention of diseases mediated by stearoyt-CoA desaturase (SCD). especially human SCD (hSCD), preferably diseases related to dysfipiderrua and disorders of lipid metabolism, and especially a disease related to elevated plasma ipid levels, especially cardiovascular disease, diabetes, obesity, metabolic syndrome and the like, by administering to a patient in need of such treatment an effective amount of an SCD-modulating, especially inhibiting, agent. In general, the present invention provides a method for treating a patient for, or protecting a patient from developing, a disease related to dyslipidemia and/or a disorder of lipid metabolism, wherein lipid levels in an animaL especsa&y a human being, are outside the normal range (i.e., abnormal lipid level such as elevated plasma lipid levels), especially levels higher than normal, preferably where said lipid is a fatty acid, such as a free or complexed fatty acid, triglycerides, phospholipids, or cholesterol, such as where LDL-cholesterol levels are elevated or HDL-cholesterol levels are reduced, or any combination of these, where said fipid-related condition or disease is an SCD-mediated disease or condition, comprising administering to an animal, such as a mammal, especially a human patient, a therapeutically effective amount of a compound of the invention or a pharmaceutical cotrposition comprising a compound of the invention wherein the compound modulates the activity of SCD, preferably human SCD1. The compounds of the invention modulate, preferably inhfcit, the activity of human SCD enzymes, especially human SCD1. The general value of the compounds of the invention in modulating, especially inhibiting, the activity of SCD can be determined using the assay described below in Example 5. Alternatively, the general value of the compounds m treating disorders and diseases may be established in industry standard animal modeis for ctemoostrating the efficacy of compounds in treating obesity, diabetes or elevated triglyceride or cholesterol levels or for improving glucose tolerance. Such modete include Zucker obese fa/fa rats (available from Harlan Sprague Dawtey Inc ;lndanapofcs Indiana)), or the Zucker diabetic fatty rat (ZDFIGm\CrV-fa/fa) (available teom Znahes River Laboratories (Montreal, Quebec)). The compounds of the instant invention are inhfoilors c* oete-9 oesarjrases and are useful for treating diseases and disorders in humans anc other organisms, including all those human diseases and disorders which are the r-su* of aberrant delta-9 desaturase biological activity or which may be ameioratec by -roiJaton of delta-9 desaturase biological activity. As defined herein, an SCD-mediated disease or condter indudes but is not limited to a disease or condition which is, or is related to, cardcvasoiar disease, dyslipidemias (including but not limited to disorders of serum tevete of triglycerides, hypertriglyceridemia, VLDL, HDL, LDL, fatty acid Desaturation index (e.g. the ratio of 18:1/18:0 fatty acids, or other fatty acids, as defined elsewhere herein), cholesterol, and total cholesterol, hypercholesterolemia, as well as cholesterol disorders (including disorders characterized by defective reverse cholesterol transport), familial combined hyperlipidemia, coronary artery disease, atherosclerosis, heart disease, cerebrovascular disease (including but not limited to stroke, ischemic stroke and transient ischemic attack (TIA)), peripheral vascular disease, and ischemic retinopathy. In a preferred embodiment, compounds of the invention wfll, in a patient increase HDL levels and/or decrease triglyceride levels and/or decrease LDL or non-HDL-chotesteroI levels. An SCD-mediated disease or condition also includes metaboic syndrome (including but not limited to dyslipidemia, obesity and insulin resistance, hypertension, microalbuminemia, hyperuricaemia, and hypercoagulability). Syndrome X. diabetes, insulin resistance, decreased glucose tolerance, non-insulin-dependent diabetes mellitus, Type II diabetes, Type I diabetes, diabetic complications, body weight disorders (including but not limited to obesity, overweight cachexia and anorexia), weight loss, body mass index and leptin related diseases. In a preferred embodiment, compounds of the invention will be used to treat diabetes mellitus and obesity. As used herein, the term "metabolic syndrome" is a recognized clinical term used to describe a condition comprising combinations of Type II diabetes, impaired glucose tolerance, insulin resistance, hypertension, obesity, increased abdominal girth, hypertriglyceridemia, low HDL, hyperuricaemia, hypercoaguiaoifity and/or microalbuminemia. An SCD-mediated disease or condition also includes fatty &ver. hepatic steatosis, hepatitis, non-alcoholic hepatitis, non-alcoholic steatohepatite (NASH). alcoholic hepatitis, acute fatty liver, fatty liver of pregnancy dnjgnnouced hepatitis, erythrohepatic protoporphyria, iron overload disorders, herectary henxchromatosis. hepatic fibrosis, hepatic cirrhosis, hepatoma and conditions r»a»c tfverex: An SCD-mediated disease or condition afeo tnciudes our s not limteG to a disease or condition which is, or is related to primary hyperthghcanbeoia or hypertriglyceridemia secondary to another disorder or disease suc^ as hyperlipoproteinemias, familial histiocytic reticulosis, fcpoproter lease rtetaency, apolipoprotein deficiency (such as ApoCII deficiency or ApoE ciefiaency). and the Bke, or hypertriglyceridemia of unknown or unspecified etiology An SCD-mediated disease or condition also includes a efisorder of polyunsaturated fatty acid (PUFA) disorder, or a skin disorder, including but not limited to eczema, acne, psoriasis, keloid scar formation or prevention, diseases related to production or secretions from mucous membranes, such as monounsaturated fatty acids, wax esters, and the like. An SCD-mediated disease or condition also includes inflammation, sinusitis, asthma, pancreatitis, osteoarthritis, rheumatoid arthritis, cystic fibrosis, and premenstrual syndrome. An SCD-mediated disease or condition also includes but is not imited to a disease or condition which is, or is related to cancer, neoplasia, rnaignancy. metastases, tumours (benign or malignant), carcinogenesis, hepatomas and the like. An SCD-mediated disease or condition also includes a condition where increasing lean body mass or lean muscle mass is desred. such as is desirable in enhancing performance through muscle building. Myopathies and ipid myopathies such as carnitine palmitoyltransferase deficiency (CPT I or CPT if) are also included herein. Such treatments are useful in humans and "m animal husbandry, including for administration to bovine, porcine or avian domestic animals ex any other animal to reduce triglyceride production and/or provide leaner meat products and/or healthier animals. An SCD-mediated disease or condition also includes a disease or condition which is, or is related to, neurological diseases, psychiatric disorders, multiple sclerosis, eye diseases, and immune disorders. An SCD-mediated disease or condition also includes a disease or condition which is, or is related to, viral diseases or infections including bat vol limited to all positive strand RNA viruses, coronaviruses, SARS virus. SARS-associated coronavirus, Togaviruses, Picornaviruses, Coxsackievirus. Yetow ^ever virus. Flaviviridae, ALPHAVIRUS (TOGAVIRIDAE) including Rubeia virus. Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan eaunne encephalitis virus, Sindbis virus, Semliki forest virus, Chikungunya virus, Crrfong nyong virus. Ross river virus, Mayaro virus, Alphaviruses; ASTROVIRIDAE rcudrc Astrovrus Human Astroviruses; CALICMRIDAE including Vesicular exanthema ctf sMne VT-JS Norwalk virus, Calicivirus, Bovine calicivirus, Pig cateivirus. Hepatite E CORONA VTRIDAE including Coronavirus, SARS virus, Avian infectious broncftte TJS 3ovie coronavirus, Canine coronavirus, Feline infectious perilonite vrus Hxar coronavirus 299E, Human coronavirus OC43, Murine hepatitis virus. Ponane «fef:»t diarrhea virus, Porcine hemagglutinating encephalomyelitis vims. Porcine transmissible gastroenteritis virus, Rat coronavirus, Turkey coronavirus. Rabbfc coronavirus. Berne virus, Breda virus; FLAVIVIRIDAE including Hepatitis C virus, West Hie virus. Yellow Fever virus, St. Louis encephalitis virus, Dengue Group, Hepatitis G virus. Japanese B encephalitis virus, Murray Valley encephalitis virus, Central European tick-borne encephalitis virus, Far Eastern tick-borne encephalitis virus, Kyasanur forest virus, Louping ill virus, Powassan virus, Omsk hemorrhagic fever virus, Kumiiinge virus, Absetarov anzalova hypr virus, llheus virus, Rocio encephalitis virus, Langat virus, Pestivirus , Bovine viral diarrhea, Hog cholera virus, Rio Bravo Group. Tyulenry Group, Ntaya Group, Uganda S Group, Modoc Group; PICORNAVlRfDAE including Coxsackie A virus, Rhinovirus, Hepatitis A virus, Encephatomyocanitis virus. Mengovirus, ME virus, Human poliovirus 1, Coxsackie B; POTYV1RIDAE including Potyvirus, Rymovirus, Bymovirus. Additionally it can be a disease or infection caused by or linked to Hepatitis viruses, Hepatitis B virus, Hepatitis C virus, human immunodeficiency virus (HIV) and the like. Treatable viral infections include those where the virus employs an RNA intermediate as part of the repicafive cyde (hepatitis or HIV); additionally it can be a disease or infection caused by or ftnked to RNA negative strand viruses such as influenza and parainfluenza viruses. The compounds identified in the instant specification inhibit the desaturation of various fatty acids (such as the C9-C10 desaturation of stearoyt-CoA) which is accomplished by delta-9 desaturases, such as stearoyi-CoA desaturase 1 (SCD1). As such these compounds inhibit the formation of various fatty acids and downstream metabolites thereof. This may lead to an accumulation of stearoyl-CoA or palmitoyl-CoA and other upstream precursors of various fatty acids; which may possibly result in a negative feedback loop causing an overall change in fatty aad metabolism. Any of these consequences may ultimately be responsible for the overaB therapeutic benefit provided by these compounds. Typically, a successful SCD inhibitory therapeutic agent w meet some or all of the following criteria. Oral availability should be at or above 20% Animal mode* efficacy is less than about 2 mg/Kg, 1 mg/Kg, or 0.5 mg/Kg and the target human dose is between 50 and 250 mg/70 Kg, although doses outside of thrs range may be acceptable.(Hmg/Kg' means milligrams of compound per kflcgrarr of body mass of the subject to whom it is being administered). The therapeutic moex The identification of compounds of the invention as SCD inhibitors was readily accomplished using the SCD enzyme and microsomal assay procedure described in Brownlie et al, supra. When tested in this assay, compounds of the HTvention had less than 50% remaining SCD activity at 10 pM concentration of the test compound, preferably less than 40% remaining SCD activity at 10 pM concentration of the test compound, more preferably less than 30% remaining SCD activity at 10 pM concentration of the test compound, and even more preferably less than 20% remaining SCD activity at 10 pM concentration of the test compound, thereby demonstrating that the compounds of the invention are potent rnhixtors of SCD activity. These results provide the basis for analysis of the structure-activity relationship (SAR) between test compounds and SCD. Certain R groups tend to provide more potent inhibitory compounds. SAR analysis is one of the tools those stalled in the art may now employ to identify preferred embodiments of the compounds of the invention for use as therapeutic agents. Other methods of testing the compounds disclosed herein are aisc readtfy available to those skilled in the art. Thus, in addition, said corracfcng may be accomplished in vivo. In one such embodiment said contacting r stec \a) s accomplished by administering said chemical agent to an anrrsaf dFfk^ieo «vtfh a triglyceride (TG>- or very low density lipoprotein (VLDt Healed asoroes and subsequently detecting a change in plasma triglyceride level r sae amma* thereby identifying a therapeutic agent useful in treating a triglyceride T3> ^ very on density lipoprotein (VLDL)-related disorder. In such embodiment tie anrr» r^ay be a human, such as a human patient afflicted with such a disorder and r neec zf u sail mart of said disorder. In specific embodiments of such in vivo processes, saic change in SCD1 activity in said animal is a decrease in activity, preferably wherein sakj SCD1 modulating agent does not substantially inhibit the biological activity of a detta-5 desaturase, delta-6 desaturase or fatty acid synthetase. The model systems useful for compound evaluation may include, but are not limited tot the use of liver microsomes, such as from mice that have been maintained on a high carbohydrate diet, or from human donors, including persons suffering from obesity. Immortalized cell lines, such as HepG2 (from human iver), MCF-7 (from human breast cancer) and 3T3-L1 (from mouse adipocytes) may also be used. Primary cell lines, such as mouse primary hepatocytes, are also useful n testing the compounds of the invention. Where whole animate are used, mice used as a source of primary hepatocyte cells may also be used wherein the mice have been maintained on a high carbohydrate diet to increase SCD activity in mirocrosomes and/or to etevate plasma triglyceride levels (i.e., the 18:1/18:0 ratio); alternatively mice on a normal diet or mice with normal triglyceride levels may be used. Mouse modete employing transgenic mice designed for hypertriglyceridemia are also avaiabie as is the mouse phenome database. Rabbits and hamsters are also useful as animal models, especially those expressing CETP (cholesteryl ester transfer protein). Another suitable method for determining the in vivo efficacy of the compounds of the invention is to indirectly measure their impact on inhibition of SCD enzyme by measuring a subject's Desaturation Index after administration of the compound. "Desaturation Index" as employed in this specification means the ratio of the product over the substrate for the SCD enzyme as measured from a given tissue sample. This may be calculated using three different equations 18:1n-9/18:C lOtec acd over stearic acid); 16:1n-7/16:0 (palmrtoleic acid over palmitic acid); and/or 16:1 n-7 + 18:1rw716:0 (measuring all reaction products of 16:0 desaturation over 16:0 substrate) Desaturation Index is primarily measured in liver or plasma triglycerides but may also be measured in other selected lipid fractions from a variety of fessues Desaturation Index, generally speaking, is a tool for plasma Bpid profffing A number of human diseases and disorders are the resjjr dt aberrant SCD1 biological activity and may be ameliorated by modulation of SCO" ooogicaf activity using the therapeutic agents of the invention. Inhibition of SCD expression may also affect the fatty aac ^onpcsibor of membrane phospholipids, as well as production or levels of tngfycendes and. cholesterol esters. The fatty acid composition of phospholipids utrr^tety determines membrane fluidity, while the effects on the composition of triglycerides and chotesterol esters can affect lipoprotein metabolism and adiposity. In carrying out the procedures of the present invention ft is erf course to be understood that reference to particular buffers, media, reagents, eels, culture conditions and the like are not intended to be limiting, but are to be read so as to include all related materials that one of ordinary skill in the art would recognize as being of interest or value in the particular context in which that discussion is presented. For example, it is often possible to substitute one buffer system or culture medium for another and still achieve similar, if not identical, results. Those of skMI in the art will have sufficient knowledge of such systems and methodologies so as to be able, without undue experimentation, to make such substitutions as wffl optimally serve their purposes in using the methods and procedures disclosed herein- Pharmaceutical Compositions of the Invention and Administration The present invention also relates to pharmaceutical composition containing the compounds of the invention disclosed herein. In one embodiment, the present invention relates to a composition comprising compounds of the invention in a pharmaceutically acceptable carrier and in an amount effective to modulate triglyceride level or to treat diseases related to dyslipidemia and disorders of lpd metabolism, when administered to an animal, preferably a mammal, most preferably a human patient. In an embodiment of such composition, the patient has an elevated lipid level, such as elevated triglycerides or cholesterol, before administration of said compound of the invention and the compound of the invention is present in an amount effective to reduce said lipid level. The pharmaceutical compositions useful herein also contain a pharmaceutical^ acceptable carrier, including any suitable diluent or excipient which includes any pharmaceutical agent that does not itself induce the production o^ antibodies harmful to the individual receiving the composition, and which may be admrustered without undue toxicity. Pharmaceutical^ acceptable carriers include, but are not Smted to Squids, such as water, saline, glycerol and ethanol, and the Bee. A thorough cfecussior of pharmaceutical^ acceptable carriers, diluents, and other excoents s presented m REMINGTON'S PHARMACEUTICAL SCIENCES fMack Pub Ce \ . current edition). Those skilled in the art know how to determine suitable aoses a the compounds for use in treating the diseases and disorders cortenptatec herein. Therapeutic doses are generally identified through a dose ranging study r humans based on preliminary evidence derived from animai studies. Doses must be sufficient to result in a desired therapeutic benefit without causing unwanted side-effects for the patient. The preferred dosage range for an animal is 0.001 mg/Kg to 10.000 mg/Kg, including 0.5 mg/Kg, 1.0 mg/Kg and 2.0 mg/Kg, though doses outside this range may be acceptable. The dosing schedule may be once or twice per day, although more often or less often may be satisfactory. Those skilled in the art are also familiar with determining administration methods (oral, intravenous, inhalation, sub-cutaneous, etc.), dosage forms, suitable pharmaceutical excipients and other matters relevant to the delivery of the compounds to a subject in need thereof. In an alternative use of the invention, the compounds of the invention can be used in in vitro or in vivo studies as exemplary agents for comparative purposes to find other compounds also useful in treatment of, or protection from, the various diseases disclosed herein. Preparation of the Compounds of the Invention It is understood that in the following description, combinations of substrtuents and/or variables of the depicted formulae are permissible onty if such contributions result in stable compounds. It will also be appreciated by those skilled in the art that in the process described below the functional groups of intermediate compounds may need to be protected by suitable protecting groups. Such functional groups include hydroxy, amino, mercapto and carboxylic acid. Suitable protecting groups for hydroxy include trialkylsilyl or diarylalkylsilyl (e.g., f-butyldimethylsilyl, f-butyldiphenylsifyl or trimethylsityl), tetrahydropyranyl, benzyl, and the like. Suitabte protecting groups for amino, amidino and guanidino include f-butoxycarborryl, benzytoxycart>orryt. and the like. Suitable protecting groups for mercapto include -CfOJ-R" (where R* is akyi, aryl or arylalkyl), p-methoxybenzyl, trityl and the like. Suitable protecting groups for carboxylic acid include alkyl, aryl or arylalkyl esters. Protecting groups may be added or removed in accordance war standard techniques, which are well-known to those skiDed in the art anc as oescribec r>eretn. The use of protecting groups is descrft>ed in detail n Greer - A arc c G.M. Wutz, Protective Groups in Organic Synthesis (1999). 3rd Ed. Wle* ~Te protecting group may also be a polymer resin such as a Wang resin or a 2 1 It will also be appreciated by those skiBed in the art aftftougr SJCT protected derivatives of compounds of this invention may not possess pharmacological activity as such, they may be administered to a mammal and thereafter metabolized in the body to form compounds of the invention which are pharmacologically active. Such derivatives may therefore be described as "prodrugs". All prodrugs of compounds of this invention are included within the scope of the invention. The following Reaction Schemes illustrate methods to make compounds of this invention. It is understood that one of those skilled in the art would be able to make these compounds by similar methods or by methods known to one skilled in the art. In general, starting components may be obtained from sources such as Sigma Aldrich, Lancaster Synthesis, Inc., Maybridge, Matrix Scientific, TCI, aid Ruorochem USA, etc. or synthesized according to sources known to those skilled in the art (see, e.g.. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. 5th edition (Wiley, December 2000)) or prepared as described in this invention. R\ R2. R3, R4, R5, R6, R7, R7a, R8, R8a, R9, R9a, R10, R10a and V are defined as in the Specification unless specifically defined otherwise. X is selected from CI or Br. PG represents a protecting group such as BOC, benzyl group and the like. In general, the compounds of formula (I) of the invention where W is -C(0)N(R1)- and V is -C(O)-, -S(0)r or -C(R11)H- can be synthesized following the general procedure as described in Reaction Scheme 1. equivalent) in a solvent, such as dichloromethane, chloroform or toluene, but not limited to, at 0°C in the presence of a base such as diisopropytethytamme. is added a solution of a compound of formula 102 (1 equivalent). The resulting mixture is stirred at ambient temperature for 8 - 24 h. The reaction ts quenched witr wafer The organic phase is washed with water, dried over a drying agent such as anhydrous Na-SO. filtered and concentrated in vacuo to yield compound (103). Compound (104): A solution of compound of formula of (1C3) aotamec above is dissolved in an adequate solvent and the protection group PG s nenwed under standard deprotection conditions such as hydrolysis or hydrogenatar i: otter: the amine of formula (104). Compound (107): To a solution of 54Tydroxypyridne-2-caocaryic aad * equivalent) in a solvent such as dichloromethane, chloroform ortoiuene s added a base such as triethylamine, diisopropylethylamine, foflowed by l-hydnxybenzotriazote monohydrate (1 equivalent) and a coupling agent (1 equivalent) suc^ as EDCl. The resulting mixture is stirred for 15 - 60 min and the amine of formica (106) (1 equivalent) is added. After stirring for 18 - 24 hours, the reaction mixture is diluted with dichloromethane, washed with water, dried over anhydrous Na2S04, filtered and concentrated in vacuo. Purification by flash chromatography yields compound (107). Compound (108): To a solution of compound of formula (107) obtained above (1 equivalent) at 0°C in a solvent such as dichloromethane is added triethylamine (1.5 to 2.5 equivalent) followed by dropwise addition of a solution of trifluoromethanesulfonic anhydride (1.1 to 1.5 equivalent) in a solvent such as dichloromethane. The resulting mixture is stirred at 0°C for 3 - 8 h and then quenched with water. The organic layer is separated, dried over anhydrous MgSO. filtered and concentrated in vacuo. Purification by flash column chromatography affords compound (108). Compound of Formula (I): This compound is obtained using BuchwaW reaction. In general, a flask under argon atmosphere is charged with a base such as cesium carbonate or potassium carbonate, palladium catalyst such as palladium diacetate and a ligand such as BINAP. A solution of compound (108) and compound (104) in toluene is added via syringe. The reaction mixture is then heated at 100°C for 26 h, cooled to ambient temperature, diluted with toluene, filtered and concentrated in vacuo. The crude product was purified via flash column chromatography affords compound of Formula (I). Alternatively, the compounds of formula (I) of the invention where W is -C(0)NH- and V is -C(O)-, -S(0)2- or -C(R11)H- can be synthesized following the the above reaction scheme as follows: Compound 116. To a stirred solution of the amine of formula (114) (1 equivalent) in a solvent such as dichloromethane or toluene is added the solution of a chloride of formula (115) (1 equivalent) in a solvent such as dichtoromethane or toluene in the presence of a base such as triethylamine or Hunigs tjase The resulting mixture is stirred at ambient temperature for an adequate time penod and then quenched with water. The organic phase is washed with H70. fame dned over and then concentrated in vacuo to afford the product of formula (116) Compound 117. A solution of compound of formula of (116) oexaned aoove is dissolved in an adequate solvent and the protection group PG is remote unoer standard deprotection conditions such as hydrolysis or hydrogenabor t obtain the amine of formula (117). Compound 119. The mixture of a pyridine compound of fbrmusa (117) (1 equivalent) and the compound of formula (118) (1.5 equivalent) in an adequate solvent is heated at reflux for 4-24 hours. To the reaction mixture is added a basic solution such as NaOH solution. The aqueous layer is extracted by an organic solvent such as dichloromethane or ethyl acetate. The combined organic phase is dried, then evaporated to dryness. The crude compound is purified by column chromatography or crystallization to afford the compound of formula (119). Compound 120. The nitro compound of formula (119) can be reduced to the corresponding amine compound of formula (120) using a standard hydrogenation process known to one skilled in the art. Compound of formula (I): Method A: To a stirred solution of compound of formula (120) (1 equivalent) in a solvent such as dichloromethane, acetonitrile or toluene is added the solution of a compound of formula (121) (1 equivalent) in the presence of a base such as triethylamine or Hunigs base (1 equivalent) at 0°C. The resulting mature is stirred at ambient temperature for 8-24 hours and then quenched with water. The organic phase is washed with H20, brine, dried and then concentrated in vacuo to.afford the compound of formula (I) where W is -C(0)NH- and V is -C(0}-, -S(0)r- or -C(R')H-. Method B: To a solution of the compound of formula (122) (1 equivalent) in a solvent such as dichloromethane, toluene or THF is added a base such as triethylamine or Hunigs base (2.5 equivalent), followed by the addition of a coupling agent such as (3-dimethylaminopropyl)ethyl carbodiimide (1.1 equivalent). The resulting mixture is stirred for 15 minutes to an hour and an amine of formula (120) (1.1 equivalent) is added. The mixture is stirred at ambient temperature for 8-24 hours, then washed with water, dried and concentrated in vacuo. Purification by column chromatography or crystallization from a suitable solvent affords the compound of formula (I) where W is -C(0)NH- and V is -0(0)-, -S(0)r or -C(FT)B- Alternatively, the compounds of formula (I) of the invention where W s -NHC(0)NH- and V is -0(0)-, -S(0)z- or -C(R11)H- can be synthesized fotowing the general procedure as described in Reaction Scheme 3. REACTION SCHEME 3 Formula (I) The starting materials for the above reaction scheme are commercially available or can be prepared according to methods known to one skSed in the art or by methods disclosed herein. In general, the compounds of the invention are prepared in the above reaction scheme as follows: Compound of formula (I). To a stirred solution of the compound of formula (120) (1 equivalent) in an anhydrous solvent such as dimethytformamide is added an isocyanate of formula (123) (3 equivalent), and the mixture is then heated to 60 - 80°C for 4 -24 hours. The mixture is concentrated in vacuo. Purification of the crude product by column chromatography or crystallization from a suitable solvent affords the compound of formula (I) where W is -NHC(0)NH- and V is -C(O)-, -S(0)r or -C(R11)H-. Alternatively, the compounds of formula (I) of the invention where W is -S(0)2NH- and V is -0(0)-, -S(0)2- or -C(R11)H- can be synthesized fotowmg the general procedure as described in Reaction Scheme 4. REACTION SCHEME 4 Formula (I) The starting materials for the above reaction scheme are commerciafly available or can be prepared according to methods known to one staled rt the art or by methods disclosed herein. In general, the compounds of the invention are prepared in the above reaction scheme as follows: Compound of formula (I): To a solution of compound of formula (118) (1 equivalent) in a solvent such as dichloromethane, acetonrtrite or toluene is added slowly the solution of compound of formula (124) (1 equivalent) at 0C- The resulting mixture is stirred at ambient temperature for 8-24 hours and then quenched with water. After removal of solvent, the product was purified by chromatography to afford the compound of formula (I) where W is -S(0)2NH- and V is -0(0)-, -S(0)2- or -C(R11)H-. PREPARATION 1 SYNTHESIS OF PIPERAZIN-1-YL-(2-TRIFLUOROMETHYLPHENYL)METHANONE A. To a stirred solution of 1-Boc-piperazine (0.50 g, 2.7 mmol) and diisopropylethylamine (1.75 g, 13.5 mmol) in dichloromethane at 0C was added a solution of 2-trifluoromethylbenzoyl chloride (0.626 g, 3.0 mmol). The resulting mbcture was stirred at room temperature for 20 h and then quenched with water (25 mL). The organic phase was washed with water, dried over anhydrous NajSO. fiftered and concentrated in vacuo to yield 4-(2-trifluoromethyIberuoyl)p«perazrTe-i B. A solution of 4^2-trifluoromethylbenzoyr)Qiperazre-H3rtx3fyfc aad ferf-butyl ester (0.948 g, 2.65 mmol) in 50 mL of a 1:4 mixture of trftjor^acebc aoc anddichloromethane was stirred at room temperature for 20 h. After concentrator i vacuo, the residue was dissolved in dichloromethane (100 mL) and wa&ncd *? * N NaOH (10 mL), water (15 mL), and brine (15 mL). The organic phase was dned over anhydrous Na2S04, filtered and concentrated in vacuo to yiekj the tide compound as a light brown oil (0.657 g, 2.54 mmol). 1H NMR (300 MHz, CDCy 5 7.69 7.54. 7.30. 3.78, 3.15, 2.94, 2.76. MS (ES+) mfr 259.3 (M+1). PREPARATION 2 SYNTHESIS OF TRIFLUOROMETHANESULFONIC ACID 6-(3- PHENYLPROPYLCARBAMOYL)PYRIDIN-3-YL ESTER A. To a solution of 5-hydroxypyridine-2-carboxylic acid (0.103 g, 0.74 mmol) in dichloromethane was added diisopropylethylamine (0.279 mL 1.6 mmol), followed by 1-hydroxybenzotriazole monohydrate (0.012 g, 0.8 mmoQ and EDCI (0.153 g, 0.8 mmol). The resulting mixture was stirred for 15 minutes and 3-phenyM- propylamine (0.108 g, 0.8 mmol) was added. After stirring for 22 h. the reaction mixture was diluted with dichloromethane (80 mL), washed with water, dried over anhydrous Na2S04and concentrated in vacuo. Purification by column chromatography afforded 5-hydroxypyridine-2-carboxylic acid (3-phenylpropyf)amkie as white crystals (0.116 g, 61% yield). MS (ES+) nVz 257.2 (M+1). B. To a solution of 5-hydroxypyridine-2-carboxyiic acid (3- phenylpropyl)amide obtained above (0.097 g, 0.378 mmol) at 0°C in efichtoromethane (5 mL) was added triethylamine (0.079 mL, 0.567 mmol) followed by dropwise addition of a solution of trifluoromethanesulfonic anhydride (0.077 mL, 0.454 mmol) in dichloromethane (2 mL). The mixture was stirred at 0°C for 5 h and quenched with water (25 mL). The organic phase was separated, dried over anhydrous MgS04, filtered and concentrated in vacuo. The residue was purified by column chromatography and the title compounds was obtained as a clear oil (0.124 g, 84% EXAMPLE 2 SYNTHESIS OF 4-PHENYL-/V-{5-[4-(2-TRIFLUOROMETHYLBENZOYL>PiPERAZIN- 1-YL]-PYRIDlN-2-YL}BUTYRAMIDE To a solution of [4-(6-aminopyridin-3-yI)pipera2irM-^^ methanone (0.035 g, 0.10 mmol) in dichloromethane was added diisopropytethylamine (0.084 ml_, 0.48 mmol), followed by 1-hydroxybenzotriazole monohydrate (0.018 g, 0.12 mmol), EDCI (0.023 g, 0.12 mmol) and DMAP (0.015 g, 0.12 mmol). The resulting mixture was stirred for 15 minutes and 3-phenyl-1-propylamine (0.020 g, 0.12 mmol) was added. After stirring for 18 h, the reaction mixture was diluted with ethyl acetate, washed with brine, dried over anhydrous MgS04, filtered and concentrated in vacuo. Purification by preparative thin layer chromatography afforded the titte compound as a pale white solid (6.2 mg, 12.5% yield). 1H NMR (300 MHz, CDCfe) 5 8.12. 7.97. 7.87. 7.72, 7.59, 7.34, 7.10-7.29, 3.98, 3.34, 3.22, 3.02, 2.70, 2.37, 2.08. MS (ES+) m/z 497.2 (M+1). EXAMPLE 2.1 The following compounds were synthesized by the similar procedure as described in Example 2: EXAMPLE 4 SYNTHESIS OF HEXANE-1-SULFONIC ACID {5-[4^2-TR!FLUOROMETHYLBENZOYL)-PIPERAZlN-1-YL]PYRIDIN-2-YL}AMlDE To a solution of [4-(6-aminopyridin-3-yi)piperazin-1-yIH^ methanone (0.035 g, 0.10 mmol) in pyridine (3 ml_) was added hexanesutfonyi chloride (0.022 mL? 0.12 mmol). After heating at 60°C for 20 h, the mixture was cSuted with ethyl acetate (100 ml_), washed with brine, dried over anhydrous MgSO* and concentrated in vacuo. Purification by preparative thin layer chromatography afforded the title compound as a white solid (3.8 mg, 8% yield). 1H NMR (300 MHz. CDCfe) 5 7.66, 7.29, 4.08, 3.91, 3.38, 3.27, 3.08,1.84, 1.35,1.27, 0.87. MS (ES+) m EXAMPLE 4.1 The following compounds were synthesized by the similar procedure as described in Example 4: Pentane-1 -sulfonic acid {5-[4-(2-trifluoromethylbenzoyl)piperazin-1-yI]pyridin-2- 3-Phenylpropane-1 -sulfonic acid {5-[4^2-trifluoromethylbenzoy1>operazin-1-y!]pyridin-2-yI}amide. EXAMPLE 5 MEASURING STEAROYL-COA DESATURASE INHIBITION ACTIVE ZF * TES' COMPOUND USING MOUSE LIVER MICROSOMES The identification of compounds of the invention as SCD inhfcrtors was readiy accomplished using the SCD enzymes and microsomal assay procedu* flescrfeog ir. Brownlie et a/, PCT published patent application, WO 01/62954. Preparation of Mouse Liver Microsomes: Male ICR mice, on a high-carbohydrate, low fat diet under Bght hatohane (15% in mineral oil) anesthesia are sacrificed by exsanguination during periods of high enzyme activity. Livers are immediately rinsed with cold 0.9% NaCI solution, weighed and minced with scissors. All procedures are performed at4°C unless specified otherwise. Livers are homogenized in a solution (1:3 w/v) containing 0.25 M sucrose, 62 mM potassium phosphate buffer (pH 7.0), 0.15 M KCI, 1.5 mM /V-acetyleysteine, 5 mM MgCI2, and 0.1 mM EDTA using 4 strokes of a Potter-Efvehjem tissue homogenizer. The homogenate is centrifuged at 10,400 x g for 20 mm to eiminate mitochondria and cellular debris. The supernatant is filtered through a 3-iayer cheesecloth and centrifuged at 105,000 x g for 60 min. The microsomal petet is gentiy resuspended in the same homogenization solution with a small glass/teflon homogenizer and stored at -70°C. The absence of mitochondrial contamination is enzymatically assessed. The protein concentration is measured using bovine serum albumin as the standard. Incubation of Mouse Liver Microsomes with Test Compounds: Reactions are started by adding 2 mg of microsomal protein to pre-incubated tubes containing 0.20 nCi of the substrate fatty acid (1-14C palmitic acid) aa a final concentration of 33.3 p.M in 1.5 ml of homogenization solution, containing 42 mM NaF, 0.33 mM niacinamide, 1.6 mM ATP, 1.0 mM NADH, 0.1 mM coenzyme A and a 10 \iM concentration of test compound. The tubes are vortexed vigorously and after 15 min incubation in a shaking water bath (37°C), the reactions are stopped and fatty acids are analyzed. Fatty acids are analyzed as follows: The reaction mixture is saponified with 10% KOH to obtain free fatty acids which are further methylated using 3F? r. methanol. The fatty acid methyl esters are analyzed by high performance liquid arornaEDgraphy (HPLC) using a Hewlett Packard 1090, Series II chromatograph eqtrippec wtfr a 3jode array detector set at 205 nm, a radioisotope detector (Mode* 171, Becianar; CA, wrtr 3 solid scintillation cartridge (97% efficiency for ^C-detecfon) and a reverse-prase DDS (C-18) Beckman column (250 mm x 4.6 mm i.d.; 5 pjn partcte size) dUu'ec to a are-column with a fjBondapak C-18 (Beckman) insert Fatty acid methyt esters are separated isocratically with acetonrtrite/water (95:5 vrv) at a flow rate erf * mL/mr anc are identified by comparison with authentic standards. Alternatively fatty add me&V esters may be analyzed by capillary column gas-chromatograpfty (GC) or Thin Layer Chromatography (TLC). Those skilled in the art are aware of a variety of modifications to this assay that can be useful for measuring inhibition of stearoyl-CoA desaturase activity in microsomes by test compounds. Representative compounds of the invention showed activity as inhibitors of SCD when tested in this assay. The activity was defined in terms of % SCD enzyme activity remaining at the desired concentration of the test compound. ***** All of the U.S. patents, U.S. patent application publications, U.S. paient applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference, in their entirety. From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of iBusiration. various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims WHAT IS CLAIMED IS 1. A method of inhibiting human stearoyf-CoA desaturase (hSCD) activity comprising contacting a source of hSCD with a compound of formula (!) wherein: x and y are each independently 1, 2 or 3: W is -O-, -N(R1h -C(Oh -S(0)r; (where t is 0,1 or2). -N(R;S/0>^. -S(0)2N(R1)-, -OS(0)2N(R1)-, -C(0)N(R1K -OC(0)N(R>, -C(S)N(R>, ^>C{S>(RV. -N(R1)C(0)- or -N(R1)C(0)N(R1)-; V is -C(O)-, -C(S)-, -C(0)N(R1)-, -C(0)0-, -S(0)2~, -S(OhN(R> or -C(R11)H-; each R1 is independently selected from the group consisting of hydrogen, d-C12alkyI, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyf and Cr-CioaraJkyl; R2 is selected from the group consisting of CrC^alkyl, C2-Ci2alkenyl, C2-Ci2hydroxyalkylt C2-C12hydroxyalkenyl, C2-C12alkoxyaikyI, C3-Ci2cydo^kyi. C4-C12cycloaikyIalkyl, aryl, Cy-dgaralkyl, C3-Ci2heterocydyi, C3-C12heterocyc)yiaJkyl. Ci-C12heteroaryl, and C3-C12heteroarylaIkyl; or R2 is a mufti-ring structure having 2 to 4 rings whereri the rings are independently selected from the group consisting of cyctoalkyl, heterocydyl. aryl and heteroaryl and where some or all of the rings may be fused to each other R3 is selected from the group consisting of (VC,2alkyl. Cr-C-^cenyi. C2-C12hydroxyalkyI, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl. Cr-Circyctoaicyl C4-C12cycIoalkylaIkyl, aryl, C7-Ci9aralkyl, C3-C12heterocycfyl, C^^heterocydylalkyt CrC12heteroaryl and C3-C12heteroarylalkyl; or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cyctoalkyl, heterocyctyi. aryl and heteroaryl and where some or all of the rings may be fused to each other; R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or-N(R13)2; R7, R7a, R8, R8a, R9, R9a, R10 and R10a are each independently selected 5. The method of Claim 4 wherein the disease or condition is Type I! diabetes. 6. The method of Claim 4 wherein the disease or condition is obesity. 7. The method of Claim 4 wherein the disease or condition s netaboic syndrome. 8. The method of Claim 4 wherein the disease or condition s fatty wwr 9. The method of Claim 4 wherein the disease or concfitior is nor-aicanoic steatohepatitis. 10. A compound of formula (Ha): C3-C12heterocyclylalkyl, d-Ci2 heteroaryl and C3-C12heteroarytaikyi; R4, R5 and R6 are each independently selected from hydrogen, ftuoro. chloro, methyl, methoxy, trifluoromethyl, cyano, nltro or-N(R'3)i: R7, R7a, RB, RBa, R9, R93, R10, and R10a are each independently selected from hydrogen or d-C3alkyl; or R9and R93 together, or R10 and R10a together form an cxc OTDUC hie the remaining R7, R7a, R8, R83, R9, R93, R10, and R10a are each independency saectec from hydrogen or CVCaalkyi; or one of R7, R7a, R10 and R10a, together with one of RP R^ =^and=^ form an alkylene bridge, while the remaining Rt0, R10a. R\ FT. R, R* R* anc R* are each independently selected from hydrogen or d-Caalkyt. and each R13 is independently selected from hydrogen or C-C-afcyt a stereoisomer, enantiomer or tautomer thereof, a pharmaceLfcay acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof 11. The compound of Claim 10 wherein: x and y are each 1; R1 is hydrogen or d-Cealkyl; R2 is selected from the group consisting of Cr-C^alky!, C3-C-2alkenyl C7-Ci2hydroxyalkyl, C2-C12alkoxyalkyl, C3-Ci2hydroxyalkenyI, C3-C12cycloafkyi, C4-Ci2cycloalkyIalkyl, C13-Ci9aralkyl, C3-C12heterocyclylalkyl, and C3-Ci2hetero^ylalkyl: R3 is selected from the group consisting of Cr-d^ky! d-C-^aicenyi. C3-C12hydroxyaIkyl, C3-C12hydroxyalkenyl, C3-C12atkoxy, d-Ci^koxya&y. C3-d2cycloalkyl, d-C^cycloalkylalkyl, aryl, Cy-C^aralkyl, C^-Ciiheterocfdtyi. C3-Ci2heterocyclylalkyl, d-Ci2 heteroaryl and C3-C12heteroarylalkyl; R4, R5 and R6 are each hydrogen; and R7, R7a, R8, R8a, R9, R93, R10, and R10a are each hydrogen. 12. A method of treating a disease or condition mediated by stearoyi-CoA desaturase (SCD) in a mammal, wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of Claim 10. 13. A pharmaceutical composition comprising a pharmaceutical^ acceptable excipient and a therapeutically effective amount of a compound of Claim 10. 14. A compound of formula (lib): wherein: x and y are each independently 1, 2 or 3: R1 is selected from the group consisting erf hydrogen. C—C«jafcy-C2-C12hydroxyaIkyl, C4-C12cycloalkylalkyt and Cr-Cigaraflcyi, R2 is selected from the group consisting of Ct-C12aflcyf, Cx-C^^afcenyt C2-C12hydroxyalkyI, C2-C12hydroxyalkenyl, d-Cealkoxy, C3-Ci2aIkoxyalkyi_ C3-Ci2cycloalkyl, C4-Ci2cycloalkylalkyl, Cr-Cigaralkyi, C^-C-.z heterocydyl. C3-C12heterocyclylalkyl, Ci-Ci2heteroaryl and C3-Ci2heteroary!alkyI; or R2 is phenyl optionally substituted with one or more substituents selected from halo and CrC6trihaloalkyl; or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocydyl, aryl and heteroaryl, where some or all of the rings may be fused to each other; R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, Ci-Cealtyl Ci-C$irihaiaaBcytT Ci-C6trihaloalkoxy, d-CealkylsuIfonyl, -N(R12)2, -OC(0)R12, -C(0)OR12, -Sp^R"2) cycloalkyl, heterocydyl, heteroaryl and heteroarylcycloalkyl, provided that R3 Js not phenyl substituted with optionally substituted thienyl; R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or-N(R13)2; R7, R7a, R8, R8a, R9, R93, R10, and R10a are each independently setected from hydrogen or C^Caalkyl; or R9and R9a together, or R10 and R10a together form an oxo group, while the remaining R7, R7a, R8, R83, R9, R9a, R10, and R10a are each independently selected from hydrogen or d-C3alkyl; or one of R7, R7a, R10 and R10a, together with one of R8, R83, Rs and R93, form an alkylene bridge, while the remaining R10, R10a, R7, R7a, R8, R83, R9, and R93 are each independently selected from hydrogen or Ci-C3alkyl; and each R12 is independently selected from hydrogen. d-daky. C3-C6cycloalkyl, aryl or aralkyl; and each R13 is independently selected from hydrogen or d-da§cyt; a stereoisomer, enantiomer or tautomer thereof, a pharmacsutica&y acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof 15. The compound of Claim 14 wherein: x and y are each 1; R1 is hydrogen or Ci-C6aBcyl; R2 is selected from the group consisting of C-C-jalkyi. Cr-C-rafceny C2-Ci2hydroxyalkylf d-C^hydroxyalkenyf, C:-C5a!koxy, d-C^aJkoxyaicy C3-Ci2cycloalkyl, d-C^cycloalkylalkyl, Cr-dgaralky!, d-C-2 helerocydyt, C3-d2heterocycIylaIkyl, d-C12heteroaryt and C3-d2heteroarytaky{; or R2 is phenyl optionally substituted with one or more subsftuerte selected from halo and Ci-C6trihaloalkyl; R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-dalkyl, d-Cetrihaloaflcyl, d-Cetrihaloalkoxy, d-C6alkylsulfonyIf -N(R12)2, -OC(0)R12, -C(0)OR12 and -S(0)2N(R12)2; R4, R5 and R6 are each hydrogen; R7, R7a, R8, R8a, R9f R9a, R10, and R10a are each hydrogen; and each R12 is independently selected from hydrogen, d-C$akyL d-dcycloalkyl, aryl or aralkyl. 16. The compound of Claim 15 wherein: R2 is C7-C12aralkyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C3alkyl and d-dtrihatoafcyt and R3 is phenyl optionally substituted by one or more substituents setected from the group consisting of halo, d-C6alkyl, d-C6trihaloalkyl and d-dtrfraioalkoxy. 17. The compound of Claim 16 selected from the group consistng of the following: 3-(4-Fluoro-phenyI)-N^5-[4-(2-trifluorom propionamide; 4-Phenyl-N^5-[4-(2-trifluoromethyl-benzoy!)^^ 4-(4-Fluoro-phenyI)-N^5-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-pyridin-2-yl)- butyramide; and ^Phenyl-N^544-(2-trifluoromethy^benzoyO 18. The compound of Claim 15 wherein: R2 is Ci-Ci2alkyl or C2-C12alkenyl; and R3 is phenyl optionally substituted by one or more substituents seteasd from the group consisting of halo, d-C6alkyl d-C6trihaloaIkyf and d-CstnhaKsafcory 19. The compound of Claim 18 setected from the group consistent of !he following: Hexanoic acid {5-[4-(24rifluoromethyt4>enzoyl}-piperaa^ Heptanoic acid {5-[4-(2-trifluoromethyt-benzoyl)-pipe^ and 5-Methylpentanoic acid {5-[4-(24rifluoromethyl-benzoyi)-piperazirh^ amide. 20. The compound of Claim 15 wherein: R2 is C3-Ci2heteroarylalkyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C3alkyl and d-Cetrihaloalkyl; and R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C6alkyl, CrC6trihaloalkyl and d-Cetrihaloalkoxy. 21. The compound of Claim 20, namely, 3-Pyridin-3-yl-N-{5^4-{2-trifluoromethyl-benzoyl)-piperazin-1-yl]-pyridin-2-y[}-propionamide. 22. The compound of Claim 15 wherein: R2 is phenyl optionally substituted with one or more substituerts selected from halo and CrC6trihaloalkyl; and R3 is phenyl optionally substituted by one or more substituents setected from the group consisting of halo, d-C6alkyl, d-C6trihaloalkyl and C1-CetrtialoaBcoxy. 23. The compound of Claim 22, namely, 4-Fluoro-N-{5-{4-(2-trifluoromethylben2oyl)piperazin-1-yl]pyridin-2-yI}benzamide. 24. A method of treating a disease or condition mediated by stearoyl-CoA desaturase (SCD) in a mammal, wherein the method comprises administering to a 29. The compound of Claim 28 wherein: R2 is Ci-C12alkyl or C2-Ci2alkenyl; and R3 is phenyl optionally substituted by one or more substituents seiected from the group consisting of halo, Ci-C6alkyl, Ci-C6trihaloalkyi and C--C^tnhajoafitoxy 30. The compound of Claim 29 selected from the group consisting dt rne following: Pentane-1-sulfonic acid {5-[4-(2-trifluoromethyi-benzoyt)^^ amide; and Hexane-1-sulfonic acid {5-[4-(2-trifluoromethyUbenzoy1)-p^ amide. 31. The compound of Claim 28 wherein: R2 is C7-C12aralkyl optionally substituted by one or more subsftue^rts selected from the group consisting of halo, d-C3aIkyi and Ci-C5trihaloalkyl: and R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, d-Cealkyl, CTCetrihaloalkyl and Ci-Cstrihatoaftcoxy. 32. The compound of Claim 31, namely, 3-Phenyl-propane-1-sulfonic acid {5-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-pyridin-2-yl}-amide. 33. A method of treating a disease or condition mediated by stearoyt-CoA desaturase (SCD) in a mammal, wherein the method comprises administer*; to a mammal in need thereof a therapeutically effective amount of a compound of Claim 26. 34. A pharmaceutical composition comprising a pharmaceutica&y acceptable excipient and a therapeutically effective amount of a compound of Oaken 26. 35. A compound of formula (IV): wherein: x and y are each independently 1, 2 or 3: Va is -C(O)-, -C(S)-, -C(0)N(RV. -C(0>0-, -S(Oh- or -$(0)-N{=>" - each R1 is independently selected from the group consist^ cf hydrogen, C^-C^alky!, C^C^hydroxyalkyl, C4-C12cyctoalkytaflcyl and Cr-C-sarafcy? R2 is selected from the group consisting of C1-Ci2a&yl, Cr-C-2akerryl. C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl1 C3-C12alkoxyalkyl, Cr-Ci2cyctoafcyytafcyt. Ci-Ci2heteroaryl and C3-C12heteroarylalkyl; or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other, R3 is selected from the group consisting of C^C^alkyl, C2-C12alkenyi, C2-Ci2hydroxyalkyl, C2-Ci2hydroxyalkenyl, C2-C12alkoxyalkyl, C3-Ci2cyctoalkyL C4-Ci2cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyI, C;rC12heterocycytaIlcyi. Ci-Ci2heteroaryl and C3-C12heteroarylalkyl; or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, ary! and heteroaryl and where some or all of the rings may be fused to each other R4, R5 and R6 are each independently selected from hydrogen, fluoro. chloro, methyl, methoxy, trifluoromethyl, cyano, n'rtroor-N(R13)2; R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently setecied from hydrogen orCi-C3alkyl; or R7 and R7a together, or R8and R8a together, or R9and R9 together, or R10 and R10a together are an oxo group, provided that when Va is -C(O)-, R7and R7a together or R8 and R8a together do not form an oxo group, while the remaining R7, R7i, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or CrC3aikyl; or one of R10, R10a, R7, and R7a together with one of R8, R8, R9 and R93 form an alkylene bridge, while the remaining R10, R10at R7, R7a, R8. Rtat Rs. and R are each independently selected from hydrogen or Ci-C3alkyi; and each R13 is independently selected from hydrogen or C—Ceaficy4; a stereoisomer, enantiomer or tautomer thereof, a pharmaceuteafry acceptable salt thereof, a pharmaceutical composition thereof or a prodrug tr>ereof 36. The compound of Claim 35 wherein: x and y are each 1; Va is -C(O)-; each R1 is independently hydrogen or d-Ceakyt: R2 is selected from the group consisting of C-d^alcyl. Cr-C-7akery. C2-C12hydroxyalkyl, C^C^hydroxyalkenyl, C;rd2aikoxyalkyf. Cr-d2cycoay C4-Ci2cycloalkylalkyl, aryl, Cr-dsaralkyl, C3-C12 heterocycty!, CrCi2heterocycMattcyl. d-C12heteroaryl and C3-C12heteroarylaIkyl; R3 is selected from the group consisting of C1-C12alkyl, C2-C^2^kenyl C2-C12hydroxyaIkyl, C2-C12hydroxyalkenyl, C2-Ci2alkoxyalkyl, C3-d2cyctoaIkyi, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyI, C3-C12heterocyctytalkyi. C-i-C12heteroaryl and C3-C12heteroarylalkyl; R4, R5 and R6 are each hydrogen; and R7, R7a, RB, R8a, R9, R9a, R10, and R10a are each hydrogen. 37. The compound of Claim 36 wherein: R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-C&alkyl, d-CetrihaJoaBcyl d-Cetrihaloalkoxy, d-C6alkylsulfonyl, -N(R12)2l -OC(0)R12, -C(0)OR12, -S(ObN(R'%. cycloalkyl, heterocyclyl, heteroaryl and heteroarylcycloalkyl; and each R12 is independently selected from hydrogen, d-daHcy. C3-C6cycloalkylf aryl or aralkyl. 38. The compound of Claim 37 wherein: R2 is d-C12alkyl or C2-C12alkenyl; and R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C6a!kyl, d-C6trihaloalkyl and d-C6trihaloalkoxy. 39. The compound of Claim 38 selected from the group consisting of the following: 1-(3-MethyI-butyl)-3^5-[4-(2-trffl^ 1 -Pentyl-3-{5-[4-(2-trifluoromethyl-benzoyl)-piperazin-1 -yf]-pyridin-2-yf}^urea; and 1 -Butyl-3-{5-[4-(2-trifluoromethyl-benzoyl}-pipera2in-1 -yl}-pyridin-2-yf}~urea. 40. The compound of Claim 37 wherein: R2 is C7-C12aralkyl optionally substituted by one or more subsfcfeients selected from the group consisting of halo, d-C3alkyi and C-Cgtrihaioa&yt: anc R3 is phenyl optionally substituted by one or more substituents «jecte.£ from the group consisting of halo, Ci-Ceallcyi, d-Cetrihaioalcyi and C-C^riTaicaic3r> 41. The compound of Claim 40 selected from the group constsfcng 3f ihe following: 1-[3-(4-Fluoro-phenyl)-propyI}-3^5-[4^2-tr^ 2-yI}-urea; 1-Phenethyl-3-{5-[4-(2-trifluoromethyl-benzoyI^ and 1-Benzyl-3^5-[4-(2-trifluoromethyl-benzoyl^ 42. A method of treating a disease or condition mediated by stearoyl-CoA desaturase (SCD) in a mammal, wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of Claim 35. 43. A pharmaceutical composition comprising a pharmaceutical^ acceptable excipient and a therapeutically effective amount of a compound of CSaim 35. 44. A compound of formula (V): wherein: x and y are each independently 1, 2 or 3; Wa is -0-, -N(R1)- or -S(0)r (where t is 0, 1 or 2); Wa is -O-; Va is -C(0)-; R1 is hydrogen or d-C5alkyI; R2 is selected from the group consisting of C-C12a!kyl. d-C-jafttenyl-C2-C12hydroxyalkyI, C2-Ci2hydroxyaIkenyI, C3-C12alkoxyalkylt Cr-C-zcyctoalky. C4-Ci2cycloalkylaIkyl, aryl, C7-C19aralkyl, C3-C12 heterocyctyl, d-C-2heterocy^ytafiry' d-Ci2heteroaryl and C3-C12heteroarylalkyl; R3 is selected from the group consrsting of d-C-jaBcyl Cr-C^-afcer** d-C^hydroxyalkyl, C2-C12hydroxyalkenyl, CVC-^lkoxyalkyl. C3-C-2cyck3alr?». C4-C12cycloalkylalkyI, aryl, d-dgaralkyl, C3-d2heterocyctyl. CrC^heterocycJytafcy d-C12heteroaryl and C3-Ci2heteroaryialkyi; R4, R5 and R6 are each hydrogen; and R7, R7a, R8, R8a, R9, R93, R10, and R10a are each hydrogen. 46. The compound of Claim 45 wherein: R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-dalkyl, Ci-C6trihatoalkyt. d-dtrihaloalkoxy, d-C6alkylsulfonyl, -N(R12)2) -OC(0)R12, -C(0)OR12, -S(0)2N(R12)2, cycloalkyl, heterocyclyl, heteroaryl and heteroarylcycloalkyl; and each R12 is independently selected from hydrogen, d-C6aIkyI, C3-C6cycloalkyl, aryl or aralkyl. 47. The compound of Claim 44 wherein: x and y are each 1; Wais-N(R1K Va is -C(O)-; R1 is hydrogen or d-dalkyl; R2 is selected from the group consisting of d-C12aIkyl, d-Ct2aikenyL C2-Ci2hydroxyalkyl, C2-C12hydroxyalkenyl, C3-C12aIkoxyalkyl, C3-d2cycloalky!. C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12 heterocyclyl, d-Ci2heterocydyta§cyi. CrC^heteroaryl and C3-C12heteroarylalkyl; R3 is selected from the group consisting of d-d^Ikyl, d-Ci^kenyi, C2-Ci2hydroxyalkyl, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl, drdzcycloalkyl, C4-C12cycloalkylaIkyl, aryl, C7-d9aralkyl, C3-Ci2heterocyclyl, d-C^heterocydylalkyl, d-C12heteroaryl and C3-C12heteroarylalkyl; R4, R5 and R6 are each hydrogen; and A pharmaceutical composition comprising a pharmaceutical^ acceptable excipient and a therapeutically effective amount of a compound of Caim 44. 53. A compound of formula (Via): x and y are each independently 1, 2 or 3; R1 is selected from the group consisting of hydrogen, C1-C12alkyt! C2-C12hydroxyalkyl, C4-C12cycloalkyIaIkyl and C7-C19aralkyl; R2 is selected from the group consisting of Cy-C^alky!, C3-C12alkenylf C7-Ci2hydroxyalkyl, C2-C12alkoxyaIkyl, C3-Ci2hydroxyaIkenyl, (VC^cycIoalkyl, C4-Ci2cycloalkylalkyl, Ci3-Ci9aralkyl, C3-Ci2heterocycIyIalkyI, and C3-C12heteroarylaJkyf; or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyctyi, ary! and heteroaryl, where some or all of the rings may be fused to each other R3 is selected from the group consisting of C3-C12alkyl, C3-C12afcenyt. C3-Ci2hydroxyalkyl, C3-C12hydroxyalkenyl, C3-C12alkoxy, C3-C12alkoxyalkyf, C3-Ci2cycloalkyl, C4-C12cycloaIkylaIkyI, aryl, C7-C19aralkyl, C3-C12heterocyctyL C3-Ci2heterocyclylalkyl, C5-C12 heteroaryl and C3-C12heteroarylaIkyl; or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyi, aryl and heteroaryl and where some or all of the rings may be fused to each other R4, R5 and R6 are each independently selected from hydrogen, fkxxo. chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or-N(R13)2; R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or d-C3alkyl; or R7 and R7a together, or R8and R8a together, or R9and R93 together, or R10 and R10a together are an oxo group, provided that when Va is -C(O)-, R7and R7a 57. A compound of formula (Vlb): wherein: x and y are each independently 1, 2 or 3; each R1 is independently selected from the group consisting of hydrogen, d-C^alkyl, C2-C12hydroxyaIkyl, C4-Ci2cyctoafkytalky1 and C-C-r^arafcy R2 is selected from the group consisting of C1-C12a8cy!, Cr-Ci2akeny. C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, d-Ci^lkoxyalkyl, d-d2cyctoalkyt, C4-Ci2cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12 heterocyclyl, d-d2heterocycytafcyl, C^C^heteroaryl and C3-C12heteroarylaIkyl; or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other; R3 is naphthyl or phenyl, each optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-C6alkyl, d-Cetrihaloalkyl, d-C6trihaIoalkoxy, d-daikylsulfonyi, -N(R12)2) -OC(0)R12, -C(0)OR12, -S(0)2N(R12)2, cycloalkyl, heterocyclyl, heteroaryl and heteroaryicycloalkyl, provided that R3 is not phenyl substituted with optionally substituted thienyl, and provided that when R3 is naphthyl, R2 can not be d-CeafcyL C2-C6hydroxyalkyl or phenyl substituted by amino; R4, R5 and R6 are each independently selected from hydrogen, fiuoro. chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or-N(R13)2; R7, R7a, R8, R8a, R9, R93, R10, and R10a are each independently selected from hydrogen ord-dalkyl; or R7 and R7a together, or R8and R8a together, or R9and R93 together, or R10 and R10a together are an oxo group, provided that when Va is -C(O)-, R7and R7s together or R8 and R8a together do not form an oxo group, while the remaining R'. R a. R8, RBa, R9, R9a, R10, and R10a are each independently selected from hydrogen or d-C3alkyl; or one of R10, R10a, R7, and R7a together with one of R8, R8a, R9 and R93 5-[4-(6-TrifluoromethyLcyclohexa-1^ carboxylic acid (2-cyclohexyl~ethyI)-amide; and 5-[4-(2-TrifIuoromethyl-benzoyl)-piperazirv1-yl]-pyridine-2^artx)xyf»c ackj cyclohexylmethyl-amide. 65. The compound of Claim 58 wherein: R2 is C3-Ci2heterocydylaIkyt optionally substituted by one or more substituents selected from the group consisting of hato, cyano, nitro. hydroxy d-Cealkyl, CrC6trihaloalkylt Ct-Cetrihaloalkoxy, C-C5aIkytsu!fonyi. -4(R2>2. -OC(0)R12, -C(0)OR12 and -S(0)2N(R12)2; R3 is phenyl optionally substituted by one or more substituents se^caec from the group consisting of halo, d-C6alkyl, Ci-Cstrihaloalkyl and C^-C^tri^oattcDxy and each R12 is independently selected from hydrogen, C?-C$a!kyt. C3-C6cycloalkyl, aryl or aralkyl. 66. The compound of Claim 65 wherein R2 is 2-piperazinylethyl optiona&y substituted by-C(0)OR12. 67. The compound of Claim 66, namely, 4-[2-({5-[4-(2-Trifluoromethyl-benzoyl)-piperazin-1-yl]-pyridine-2^arbonyl}-amino)^thyl]-piperazine-1-c3rtx3xylica^ tert-butyl ester. 68. The compound of Claim 58 wherein: R2 is CrC12araIkyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C^Iky! and Ci-C6trihaloa!kyl; and R3 is naphthyl optionally substituted by one or more substituents selected from the group consisting of halo, Ci-C6alkyl, C^Cetrihaloalkyl and d-Cetrihaloalkoxy. 69. The compound of Claim 68 selected from the group consisting of the following: 5-[4-(Naphthalene-1-carbonyl)-piperazin-1-yl]-pyridine-2-carboxylicackj (3-phenyf- propyl)-amide; and 5-[4-(Naphthalene-1-carbonyl)piperazin-1-yl]pyridine-2-carboxylicacid phenethylamide. 70. A method of treating a disease or condition mediated by stearoyt-CoA desaturase (SCD) in a mammal, wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of Ctarn 57 71. A pharmaceutical composition comprising a pharmaceutical^ acceptable excipient and a therapeutically effective amount of a compound Off Claim 57.

Full Text

PYRIDYL DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS
FIELD OF THE INVENTION
The present invention relates generafty tc the fieW of inhibitors of stearoyl-CoA desaturase, such as pyridine derivatives, and uses for such compounds in treating and/or preventing various human diseases nckxJng those mediated by stearoyl-CoA desaturase (SCD) enzymes, preferably SCD! esoeciaiy cfeeases related to elevated lipid levels, cardiovascular disease diabetes aoesry netabofec syndrome and the like.
BACKGROUND OF THE INVENTION
Acyl desaturase enzymes catalyze the taraatari of double bonds in fatty acids derived from either dietary sources or de novo synthesis in the liver. Mammals synthesize at least three fatty acid desaturases of Offering chain length specificity that catalyze the addition of double bonds at the detta-9 detta-5; and delta-5 positions. Stearoyl-CoA desaturases (SCDs) introduce a double bond in the C9-C10 position of saturated fatty acids. The preferred substrates are palmrtoyl-CoA (16:0) and stearoyl-CoA (18:0), which are converted to palmitoleoyl-CoA (16:1) and oleoyl-CoA (18:1), respectively. The resulting mono-unsaturated fatty acids are substrates for incorporation into phospholipids, triglycerides, and cholesteryl esters.
A number of mammalian SCD genes have been cloned. For example, two genes have been cloned from rat (SCD1, SCD2) and four SCD genes have been isolated from mouse (SCD1, 2, 3, and 4). Whie the basic biochemical role of SCD has been known in rats and mice since the 1970s (Jeffcoat R. et a/., Elsevier Science (1984), Vol, 4, pp. 85-112; de Antueno, RJ. Upkis (1993), Vol. 28, No. 4, pp. 285-290), it has only recently been directly implicated in human disease processes.
A single SCD gene, SCD1, has been characterized in humans. SCD1 is described in Brownlie et a/, PCT published patent application, WO 01/62954, the disclosure of which is hereby incorporated by reference in its entirety. A second human SCD isoform has recently been identified, and because it bears little sequence homology to alternate mouse or rat isoforms it has been named human SCD5 or hSCD5 (PCT published patent appfcation, WO 02/26944, incorporated herein by reference in its entirety).
To date, no small-moteculet drug-like compounds are known that specifically inhibit or modulate SCD activity. Certain long-chain hydrocarbons have been used historically to study SCD activity. Known examples include thia-fatty acids,

cycbpropenoid fatty acids, and certain conjugated iinoteic acid Isomers. Specifically, c/s-12, frans-10 conjugated Iinoteic acid is believed to inhibit SCD enzyme activity and reduce the abundance of SCD1 mRNA whfie c?s-9 trans-l 1 conjugated linoleic acid does not Cycbpropenoid fatty acids, such as those found in stercula and cotton seeds, are also known to inhibit SCD activity Few example, sterculic acid (8-(2-octylcyclopropenyl)octanoic add) and ma*vafoc acid fM2-oc*yteydopropenyI)heptanoic acid) are C18 and C16 derivatives of stercuoy and mafrvaioyl fatty acids, respectively, having cyclopropene rings at ther C9-C1C aostean These agents are believed to inhibit SCD enzymatic activity by direct rteradcr win ihe enzyme, thus inhibiting delta-9 desaturation. Other agents that may mi* SCD activity include thia-fatty acids, such as S-thiastearic acid (also caiec 3-noryihocctanoic acid) and other fatty acids with a sutfoxy moiety.
These known modulators of detta-9 desaturase activity are not useful for treating the diseases and disorders linked to SCD1 biological activity. None of the known SCD inhibitor compounds are setective for SCD or defta-9 desaturases, as they also inhibit other desaturases and enzymes. The thia-fatty acids, conjugated linoleic acids and cyclopropene fatty acids (mafvalic acid and sterculic acid) are neither useful at reasonable physiological doses, nor are they specific inhibitors of SCD1 biological activity, rather they demonstrate cross inhibition of other desaturases, in particular the delta-5 and delta-6 desaturases by the cyclopropene fatty acids.
The absence of small molecule inhibitors of SCD enzyme activity is a major scientific and medical disappointment because evidence is now compelling that SCD activity is directly implicated in common human disease processes: See e.g., Attie, A.D. ef a/., "Relationship between stearoyt-CoA desa&jrase activity and plasma triglycerides in human and mouse hypertriglyceridemia", J. Lipid Res. (2002), Vol. 43, No. 11, pp. 1899-907; Cohen, P. et a/., "Rote for stearoyt-CoA desaturase-1 in leptin-mediated weight loss", Science (2002), VoL 297. No. 5579, pp. 240-3, Ntambi, J. M. et a/., "Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity", Proc. Natl. Acad. Sci. USA. (2002), Vol. 99, No. 7. pp. 11482-6.
The present invention solves this problem by presenting new classes of compounds that are useful in modulating SCD activity and regulating lipid levels, especially plasma lipid levels, and which are useful in the treatment of SCD-mediated diseases such as diseases related to dyslipktemia and disorders of lipid metabolism, especially diseases related to elevated lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome and the like.

Related Literature
PCT Published Patent Application WO 01 ^96327 discloses novel benzamide derivative compounds. PCT Published Patent Aop&caiions. WO 03/075929, WO 03/076400 and WO 03/076401, disclose compounds having histone deacetylase inhibiting enzymatic activity.
BRIEF SUMMARY OF THE INVENTION
The present invention provides pyntine 3ervatn« that modulate the activity of stearoyJ-CoA desaturase. Methods of usng sue? oerrvafc«s to modulate the activity of stearoyl-CoA desaturase and pharmaceutical zamacs&ans comprising such derivatives are also encompassed
Accordingly, in one aspect, the inventor provides methods of inhibiting human stearoyl-CoA desaturase (hSCD) activity comprising contacting a source of hSCD with a compound of formula (I):
■ * * *
wherein:
x and y are each independently 1, 2 or 3:
W is -0-, -N(R1)-, -C(OK -S(0)r; (where t is 0. 1 or 2), -N(R1)S(0)2-, -S(0)2N(R1)-, -OS(0)2N(R1)-, -C(0)N(R1K -OCr -C(S)N(R1h -0C(S)N(R1)-, -N(R1)C(0)- or -N(R1)C(0)N(R1}-;
V is -C(O)-, -C(S)-, -CCOJNCR'K -C{0)0-. -S(0)2-. -S(0)2N(R1)- or -C(R11)H-;
each R1 is independently selected from the group consisting of hydrogen, d-C^alkyl, C2-C12hydroxyalkyl, C*-C12cycloalcytalcyl and C7-Ci9aralkyl;
R2 is selected from the group consisting of Cr-Ci2alkyit C^C^alkenyl, C2-C12hydroxyaIkyl, C2-C12hydroxyalkenyi, Cs-C-pakoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, Cx-C12heterocyctyl, C3-C12heterocyclylalkyl, CrC^heteroaryl, and C3-C12heteroarylalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl and where some or all of the rings may be fused to each other;

x and y are each independently 1. 2 or 3;
R1 is selected from the group consisting of hydrogen. C-rC^alkyl, C2-Ci2hydroxyalkyl, C4-Ci2cycloalkytalkyi and C-Coaralkyt:
R2 is selected from the group consisting o? C7-C-?aIkyi. C3-C12alkenyl, C7-Ci2hydroxyalkyl, Ci-C^lkoxy, Cz-C*2a!fcaxya*cyi Cr-C-2*Tydroxyalkenyl, Cs-C^cycloalkyl, C4-Ci2cydoaftcytallcy1T C-rC-»aralryt. C-C-rheteroaryl, C3-Ci2heterocyclylalkyl and Cr-C^heteroarytaky: Drovbec that R* is not pyrazinyl, pyridinonyl, pyrrolidinone or trrwdazotyi
or R2 is a mufti-ring structure having 2ti *Tngs wherein the rings are independently selected from the group consssng df cyaoakyi. heterocyclyl, aryl and heteroaryl, where some or ail of the rings may oe fusee ID each other
R3 is selected from the group consstng of d-C-^aicyt. Cr-C12alkenyl, C3-Ci2hydroxyalkyl, Cy-C^hydroxyalkenyL Cr-C-jafcoxy. Cr-C-2aIkoxyaIkyl, C3-C12cycloalkyt, C4-Ci2cydoaIkylalkyt, aryl. C—C-^arafcyt. Cr-C^heterocyclyl, C3-Ci2heterocyclylalkylt Ci-Ci2heteroaryl and Cr-Czheteroaryialkyl;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or-N(R'3}2;
R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or d-Csalkyl;
or R9and R9a together, or R10 and R10a together form an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9*, R10, and R10a are each independently selected from hydrogen or CrC3allcyl;
or one of R7, R7a, R10 and R10at together with one of Rs, R83, R9 and R9a, form an alkylene bridge, while the remaining R10, R,Q*. R\ R7a. Re. R8*, R9, and R9a are each independently selected from hydrogen or Cr-Q^alkyt; and
each R13 is independently selected from hydrogen or d-CgalkylJ
a stereoisomer, enantiomer or tautomer thereof, a pharmaceutical^ acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.
In another aspect, the invention provides compounds of formula (I) having the following formula (lib):

administering to the mammal in need thereof a therapeutically effective amount of a compound of the invention as set forth above
In another aspect, the invention provides compounds or pharmaceutical compositions useful in treating, preventing and'or diagnosing a disease or condition relating to SCD biological activity such as the diseases encompassed by cardiovascular disorders and/or metabolic syndrome rmciuding dysiipidemia, insulin resistance and obesity).
In another aspect the invention provides meCxxis of preventing or treating a disease or condition related to elevated Epid tevcs suer as Dtasrra 6p*d levels, especially elevated triglyceride or chotestero* ievete r a patera afflicted with such elevated levels, comprising administering to sati pabert a therapeutically or prophylactically effective amount of a compositor as cfcctosed herein. The present invention also relates to novel compounds having therapeutic abSty to reduce lipid levels in an animal, especially triglyceride and choiesteroi tevete.
In another aspect, the invention provides pharmaceutical compositions comprising the compounds of the invention as set forth above, and pharmaceutically acceptable excipients. In one embodiment, the present invention relates to a pharmaceutical composition comprising a compound of the invention in a pharmaceutically acceptable carrier and in an amount effective to modulate triglyceride level, or to treat diseases related to dysiipidemia and disorders of lipid metabolism, when administered to an animal, preferably a mammal, most preferably a human patient. In an embodiment of such composition, the patient has an elevated lipid level, such as elevated plasma triglycerides or cholesterol before administration of said compound and said compound is present in an amount effective to reduce said lipid level.
In another aspect, the invention provides methods for treating a patient for, or protecting a patient from developing, a disease or condition mediated by stearoyl-CoA desaturase (SCD), which methods comprise administering to a patient afflicted with such disease or condition, or at risk of developing such disease or condition, a therapeutically effective amount of a compound that rtitoits activity of SCD in a patient when administered thereto.
In another aspect, the invention provides methods for treating a range of diseases involving lipid metabolism utilizing compounds identified by the methods disclosed herein. In accordance therewith, there is disclosed herein a range of compounds having said activity, based on a screening assay for identifying, from a library of test compounds, a therapeutic agent which modulates the biological activity

of said SCD and is useful in treating a human disorder or condition relating to serum levels of lipids, such as triglycerides, VLDL, HDL. LDu and/or total cholesterol.
DETAILED DESCRPTION OF THE INVENTION
Definitions
As used in the specification and appended csarrs unless specified to the contrary, the following terms have the meaning nn1r w r~
Certain chemical groups named herein a-e zrocedec t* a shorthand notation indicating the total number of carton atoms that ar» t be kxrta r the indicated chemical group. For example; Cr-C-jafkyl describes an afty group, as defined below, having a total of 7 to 12 carbon atoms, and C Accordingly, as used in the specification and appended claims, unless specified to the contrary, the following terms have the meaning indicated:
"Methoxy" refers to the -OCH3 radical.
"Cyano" refers to the -CN radical.
"Nitro" refers to the -N02 radical.
"Trifluoromethyr refers to the -CF3 radical.
"Oxo" refers to the =0 substituent
Thioxo" refers to the =S substituenL
"Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containrnj no unsaturation, having from one to twelve carbon atoms, preferably one to eight carbon atoms or one to six carbon atoms, and which is attached to the rest of the motecule by a single bond, e.g., methyl, ethyl, n-propyl, 1-methylethyl (/so-propyl), n-butyl, n-pentyl 1.1-dimethytethyI (f-butyl), and the like. Unless stated otherwise specifically in the specification, an alkyl group may be optionally substituted by one of the following groups: alkyt, akenyi, halo, haloalkenyl, cyano, nitro, aryl, cyctoalkyi heterocyclyL heteroaryl, -OR14, -OC(0)-R14, -N(R14)2, -C(0)R14, -C(0)OR14, -C(0)N(R14)2) -N(R14>C(0)OR16, -N(R14)C(0)R16, -N(R14)(S(0)tR16) (where t is 1 to 2), -S(0)tOR16 (where t is 1 to 2), -S(0)tR16 (where t is 0 to 2), and -S(0)tN(R14)2 (where t is 1 to 2) where each R14 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycioalkylalkyl, aryl (optionaily substituted with one or more halo groups), aralkyl, heterocyclyl, heterocytyialkyl, heteroaryl or heteroarylalkyl; and

each R16 is alkyl, haloalkyl, cycloalkyi. cydoalkytaifcyi. ay. aralkyl. heterocyclyl, heterocytylalkyl, heteroaryl or heteroarytaftcyi. and where each of the above substituents is unsubstrtuted unless otherwise indicated
nCi-C3alkyln refers to an alkyl radical as defined above containing one to three carbon atoms. The C-rC3alkyi radical may be opbona&y substituted as defined for an alkyl group.
Xi-CealkyT refers to an aBcyt radical as definec aoove containing one to six carbon atoms. The Ci-CeaJkyI radical may be opeonai* subsfc&aed as defined for an alkyl group.
"C^-CnzalkyT refers to an afcyi radical as aefoetf above containing one to twelve carbon atoms. The d-Cijalkyi radical may oc actanaK substituted as defined for an alkyl group.
"C2-C6alkyl" refers to an alkyl radical as defriec above containing two to six carbon atoms. The C^Cealkyl radical may be opfonafty substituted as defined for an alkyl group.
"C3-C6alkyT refers to an alkyl radical as defined above containing three to six carbon atoms. The C3-C6alkyl radical may be optionally substituted as defined for an alkyl group.
"C3-C12alkyr refers to an alkyl radical as defined above containing three to twelve carbon atoms. The C3-Ci2alkyl radical may be optionally substituted as defined for an alkyl group.
"Ce-C^alkyl" refers to an alkyl radical as defined above containing six to twelve carbon atoms. The C6-Ci2alkyl radical may be opfonaly substituted as defined for an alkyl group.
"Cy-C^alky!" refers to an alkyl radical as defined above containing seven to twelve carbon atoms. The C7-C12alkyl radical may be optionally substituted as defined for an alkyl group.
"Alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, contarwng at feast one double bond, having from two to twelve carbon atoms, preferably one to eight carbon atoms and which is attached to the rest of the molecule by a single bond, e.g., ethenyl, prop-1-enyl, but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the Bee. Unless stated otherwise specifically in the specification, an alkenyi group may be optionally substituted by one of the following groups: alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, -OR14, -OC(0)-R14, -N(R14)2, -C(0)R1\ -C(0)OR14, -C(0)N(R14)2,

-N(R14)C(0)0R1S, -N(R14)C(0)R16, -N(R,4)(S(0>:R**i twnere t is I to 2), -S(0)tOR16 (where t is 1 to 2), -S(0)tR1$ (where t is 0 to 2). and -& Opfi(R^h iwhere t is 1 to 2) where each R14 is independently hydrogen, alkyl, hatoafcyi. cydoalkyl, cycloalkylalkyl, aryl, aralkyi, heterocyclyl, heterocyfytattcyt, heteroary* or ^eteroarytaikyl; and each R16 is alkyl, haloalkyl, cydoalkyl, cyctoafkytaflcyi, aryl, arakyi heterocydyi. heterocyclylalkyl, heteroary! or heteroarylalkyl, and where each of the abwe substtuents is unsubstituted.
"C3-C12alkenyT refers to an afcenyt ra&cai as defined aoove containing three to 12 carbon atoms. The Cr-Ci^^eny! radical may oe jcftcrtaK substituted as defined for an alkenyl group.
"C2-C12alkenyT refers to an akenyt racfca as aenned above containing two to 12 carbon atoms. The C2-C12alkenyl radical may be ocnonatf substituted as defined above for an alkenyl group.
"Alkyiene" and "alkyiene chain" refer to a strawft: or branched divalent hydrocarbon chain, linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturate and having from one to twelve carbon atoms, preferably having from one to eight carbons, e.g., methylene, ethylene, propylene, n-butylene, and the like. The alkyiene chain may be attached to the rest of the molecule and to the radical group through one carbon within the chain or through any two carbons within the chain.
"Alkenylene" and "alkenylene chain" refer to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one doidDie bond and having from two to twelve carbon atoms, e.g., ethenylene, propenytene. r?-bufcenytene, and the like. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a double bond or a single bond. The points of attachment of the alkenylene chain to the rest of the motecute and to the radical group can be through one carbon or any two carbons within the chain.
"Alkyiene bridge" refers to a straight or branched divalent hydrocarbon bridge, linking two different carbons of the same ring structure, consisting solely of carbon and hydrogen, containing no unsaturation and having from one to twelve carbon atoms, preferably having from one to eight carbons, e.g., methylene, ethylene, propylene, n-butylene, and the like. The alkyiene bridge may fink any two carbons within the ring structure.
"Alkoxy" refers to a radical of the formula -ORa where Ra is an alkyl radical as defined above. The alkyl part of the alkoxy radical may be optionally substituted as

defined above for an alkyl radical.
"Ci-C6alkoxy" refers to an atkoxy radical as defined above containing one to six carbon atoms. The alkyl part of the C-Csa!koxy radical may be optionally substituted as defined above for an alkyl group.
"d-C^alkoxy" refers to an afcoxy radical as defined above containing one to twelve carbon atoms. The alkyl part of the Ct-C-?afccxy 'aiScai may be optionally substituted as defined above for an afcyf group
"Cr-C^lkoxy" refers to an akoxy radical as aennec above containing three to twelve carbon atoms. The alkyl part of the Cr-C-rahrav radical "nay be optionally substituted as defined above for an aicyi group.
"AlkoxyalkyT refers to a radical of the formes -R^-O-Ra wrfiere each Ra is independently an alkyl radical as defined above The cancer atom may be bonded to any carbon in either alkyl radical. Each afcyl part of the aJkoxyaJkyf radical may be optionally substituted as defined above for an aflcyi group.
wC2-Ci2alkoxyalkyr refers to an alkoxyalkyi radical as defined above containing two to twelve carbon atoms. Each alkyl part of the Cj-C-rakoxyalkyl radical may be optionally substituted as defined above for an alkyl group.
"C3alkoxyalkyr refers to an alkoxyalkyi radical as defined above containing three carbon atoms. Each alkyl part of the C3alkoxyalkyl radical may be optionally substituted as defined above for an alkyl group.
"C3-Ci2alkoxyalkyr refers to an alkoxyalkyi radical as defined above containing three to twelve carbon atoms. Each alkyl part of the Cr-C-^aBcoxyalkyl radical may be optionally substituted as defined above for an alkyl group.
"Alkylsulfonyl" refers to a radical of the formula -^O^Ra where Ra is an alkyl group as defined above. The alkyl part of the alkylsulfonyl radical may be optionally substituted as defined above for an alkyl group.
MCi-C6alkyIsulfonyr refers to an alkyisutfonyf radical as defined above having one to six carbon atoms. The Ci-Cealkybulfonyl group may be optionally substituted as defined above for an alkylsulfonyl group.
"Aryl" refers to aromatic monocyclic or multicycle hydrocarbon ring system consisting only of hydrogen and carbon and containing from 6 to 19 carbon atoms, preferably 6 to 10 carbon atoms, where the ring system may be partially or fully saturated. Aryl groups include, but are not limited to groups such as fluorenyl, phenyl and naphthyl. Unless stated otherwise specifically in the specification, the term "aryl" or the prefix "ar-" (such as in "aralkyl") is meant to include aryl radicals optionally substituted by one or more substrtuents selected from the group consisting of alkyl,

alkenyl, halo, haloalkyl, haloalkenyi. cyano. nitro. aryi aralkyi. cyctoalkyl. cycloalkyialkyi, heterocyclyl, heterocyclytalkyt, heteroaryt. beteroarytalkyl, -R15-OR14, -R^-OCODH*14, -R15-N(R14)2, -R15-C(0)R14. -R15-C(0)OR14. -R*£-C(0)N(R14)2, -Rl5-N(R14)C(0)OR16, -R15-N(R14)C(0)R16, -R15-N(R"4>fS (where t is 1 to 2), -R15-S(0)tOR16 (where t is 1 to 2), -R15-S(0)rR16 (where :S3ID 2). and -R15-S(0)tN(R14)2 (where t is 1 to 2) where each R'* is nbependenSy hydrogen, alkyl, haloalkyi, cycloalkyl, cycloalkyialkyi, aryi. aralkyi, heterocycJyL neterocyctylalkyl, heteroaryl or heteroarylalkyt: each R*£ is ndependentv a 3rec: bond or a straight or branched alkytene or alkenyiene chain, and each ~~* s afcyi u,aioalcy(, cydoalkyl, cycloalkyialkyi, aryi, aralkyi, heterocyctyi, heterocyoytairy1 neteroaryi or heteroarylalkylt and where each of the above substitiente is jnsubsttuted.
"Aralkyl" refers to a radical of the formula -R#Re »r>ere R^san alkyl radical as defined above and Rb is one or more aryi radicab as defined above, e.g., benzyl, diphenylmethyl and the like. The aryi part of the araicy racScal may be optionally substituted as described above for an aryi group. The afcyi part of the aralkyi radical may be optionally substituted as defined above for an alcyl group.
"Cr-C^aralkyl" refers to an aralkyi group as defied above containing seven to twelve carbon atoms. The aryi part of the C7-C12aralkyl radical may be optionally substituted as described above for an aryi group. The alkyl part of the Cr-C^aralkyl radical may be optionally substituted as defined above for an alkyl group.
"C7-C19aralkyr refers to an aralkyi group as defkied above containing seven to nineteen carbon atoms. The aryi part of the C7-C-.oaraicyl radical may be optionally substituted as described above for an aryi group. The aflcyl part of the Cy-C^aralkyl radical may be optionally substituted as defined above for an alkyl group.
"Ci3-C19aralkyr refers to an aralkyi group as defined above containing thirteen to nineteen carbon atoms. The aryi part of the C:r-C79araBcyl radical may be optionally substituted as described above for an aryi group. The afeyl part of the C13-C19aralkyl radical may be optionally substituted as defined above for an alcyl group.
"Aralkenyl" refers to a radical of the formula -RcR« where Re is an alkenyl radical as defined above and Rb is one or more aryi radicab as defined above, which may be optionally substituted as described above. The aryi part of the aralkenyl radical may be optionally substituted as described above for an aryi group. The alkenyl part of the aralkenyl radical may be optionally substituted as defined above for an alkenyl group.
"Aryloxy" refers to a radical of the formula -ORb where Rb is an aryi group as defined above. The aryi part of the aryloxy radical may be optionally substituted as defined above.

"Aryl-d-Cealkyl" refers to a radical of the for-nuia -R.-R where Rh is an unbranched alkyl radical having one to six carbons and R is an aryf group attached to the terminal carbon of the alkyl radical.
"CycloalkyT refers to a stable norvaromatic monocycfc or bicyciic hydrocarbon radical consisting solely of carbon and hydrogen atoms havmg from three to fifteen carbon atoms, preferably having from three to twelve cartor atoms and which is saturated or unsaturated and attached to the rest c* the p-oiecuie by a single bond, e.g., cyclopropyl, cyctobutyi, cyctoperrtyl cydoheary oecmrrrf and the Bee. Unless otherwise stated specifically in the specification the terr "rycicafcy 5 meant to include cycloalkyl radicals which are opbonafty subs&ued ny one or more substituents selected from the group consisting of alkyl. afcery. ftaic raicaicy. haioalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloaftcyialkyl. beterocycV "*eterocyc*ytalky1, heteroaryl, heteroarylalkyl, -R15-OR14, -R15-OC(0>-R14, -R1£-N(R~}- -R*£-C/0>R'4, -R15-C(0)OR14, -R15-C(0)N(R14)2, -R15-N(R14)C(0)OR16, -R15-N(R")C/0)RT -R*--N(R14)(S(0)tR16) (where t is 1 to 2), -R15-S(0)tOR16 (where t is 1 to 2), -R^-StOrR16 (where t is 0 to 2), and -R15-S(0)tN(R14)2 (where t is 1 to 2) where each R"4 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryi, aralkyl heterocydyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; each R15 is independently a direct bond or a straight or branched alkylene or alkenylene chain; and each R16 is alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl, and where each of the above substituents is unsubstituted.
"C3-C6cycloalkyr refers to a cycloalkyl radical as defined above having three to six carbon atoms. The C3-C6cycloalkyl radical may be optionaRy substituted as defined above for a cycloalkyl group.
"C3-C12cycIoaIkyl" refers to a cycloalkyl radical as defined above having three to twelve carbon atoms. The C3-C12cycloalkyl radical may be optionally substituted as defined above for a cycloalkyl group.
"Cycloalkylalkyl" refers to a radical of the forcmia -RaRc where Ra is an alkyl radical as defined above and Rd is a cycloalkyl radical as defined above. The cycloalkyl part of the cycloalkyl radical may be optionaBy substituted as defined above for a cycloalkyl radical. The alkyl part of the cycloalkyl radical may be optionally substituted as defined above for an alkyl radical.
"C4-C12cycloaIkylalkyr refers to a cycloalkylalkyl radical as defined above having four to twelve carbon atoms. The C4-C12cyctoalkylalkyl radical may be optionally substituted as defined above for a cycloalkylalkyl group.
"Halo" refers to bromo, chloro, fluoro or iodo.

"Haloalkyl" refers to an alkyl radical, as defined above, that rs substituted by one or more halo radicals, as defined above, e.g.. triftxrometfryt. difluorornethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyt-2-fkioroethyt. 3-bromo-2-fluoropropyl, 1-bromomethyi-2-bromoethy* and the fike The alkyl part of the haloalkyl radical may be optionally substituted as defined above for an alkyl group.
"Haloalkenyl" refers to an alkenyl radical, as defined above that is substituted by one or more halo radicals, as defined above, e.g 2-srorroethenyi, 3-bromoprop-1-enyl, and the like. The alkenyl part of the haioakery jLaoa n^ay se optionally substituted as defined above for an akyl group
"HeterocyclyT refers to a stable 3- to 1S-memoerec nor-aromafcc ring radical which consists of carbon atoms and from one to five "weroafcrns selected from the group consisting of nitrogen, oxygen and sulfur. For purposes of this invention, the heterocyctyl radical may be a monocyclic, bicycfc. tricycic ortetracycfic ring system, which may include fused or bridged ring systems: and the nitrogen, carbon or sulfur atoms in the heterocyclyl radical may be optionally oxkfeed; the nitrogen atom may be optionally quaternized; and the heterocyclyl radical may be partially or fully saturated. Examples of such heterocyclyl radicals include, but are not limited to, dioxolanyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyi, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyi, 2-oxopiperidinyl, 2-oxopyrroIidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1*dioxo-tHomorpho&TyI. Unless stated otherwise specifically in the specification, the term "heterocydyT is meant to include heterocyclyl radicals as defined above which are optbraly substiuted by one or more substituents selected from the group consisting of akyt alkenyl, hato, haloalkyl, haloalkenyl, cyano, oxo, thioxo, nitro, aryl, aralkyi, cydoaflcyl, cycloalkylalkyi, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalcyt. -R15-OR~, -R15-OC(0)-R14, -R15-N(R14)2, -R15-C(0)R14, -R15-C(0)OR14, -R15-C{0)N(R1*)2, -R15-N(R14)C(0)OR16, -R15-N(R14)C(0)R16, -R15-N(R14)(S(0)tR16) (where t is 1 to 2). -R15-S(0)t0R16 (where t is 1 to 2), -R15-S(0)tR16 (where t is 0 to 2), and -R15-S(0)*N(R14>2 (where t is 1 to 2) where each R14 is independently hydrogen, alkyl, alkenyl, hatoaicyi, cycloalkyi, cycloalkylalkyi, aryl, aralkyi, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; each R15 is independently a direct bond or a straight or branched afkytene or alkenytene chain; and each R16 is alkyl, alkenyl, haloalkyl, cycloalkyi, cycloalkytalkyl, aryl, aralkyi, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl, and where each of the above substituents is unsubstituted.

"C3-C12heterocycty!" refers to a heterocyctyi radical as defined above having three to twelve carbons. The C3-C-2heterocycty1 may be optona&y substituted as defined above for a heterocyctyl group.
"HeterocyctylalkyH refers to a radical of the forrouta -R»R« where Ra is an alkyl radical as defined above and Re is a helerocydyi racfica? as defined above, and if the heterocyctyl is a nitrogen-containing heterocydyl the beterocycty! may be attached to the alkyl radical at the nitrogen atom. The afkyi part of tn heterocyc*y*aIkyi radical may be optionally substituted as defined above for an air/ jnxc ^"he heterocyctyl part of the heterocyctytalkyl radical may be opfooaK sjfcsbfcjled as defined above for a heterocyctyl group.
"C3-C12heterocycfytalkyr refers to a heteroc^MaHry raeScai as defined above having three to twelve carbons. The C3-C^?heterocyciytairy "Heteroaryl" refers to a 5- to 18-membered aromatic mg radical which consists of carbon atoms and from one to five heteroatoms setected from the group consisting of nitrogen, oxygen and sulfur. For purposes of this invention, the heteroaryl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused or bridged ring systems; and the nitrogen, carbon or sulfur atoms in the heteroaryl radical may be optionally oxidized; the nitrogen atom may be optionally quatemized. Examples include, but are not limited to, azeptnyl, acridinyl, benzimidazolyl, benzthiazolyl, benzindolyl, benzothiadiazolyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl. benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothaophenyf), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl. tinnoTinyi. cSbenzofuranyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indolyi, indazolyl, tsoindoJyt indofinyt, isoindolinyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazofyl, 2-oxoazepinyi, oxazolyl, oxiranyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl pteridinyi, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, qurazofinyi quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, thiazoh/i, thiadiazxtfyL triazolyl. tetrazolyl, triazinyl, and thiophenyl. Unless stated otherwise specificafly in the specification, the term "heteroaryl" is meant to include heteroaryl radicate as defined above which are optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, oxo, thioxo, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyctyl, heterocyclytalkyl, heteroaryl, heteroarylalkyl, -R15-OR14, -R15-OC(0)-R14, -R15-N(R14)2, -R15-C(0)R14, -R15-C(0)OR14, -R15-C(0)N(R14)2) -R15-N(R14)C(0)OR16, -R15-N(R14)C(0)R16, -R15-N(R14)(S(0)tR16)

(where t is 1 to 2), -R15-S(0)tOR16 (where t is 1 to 2). -R "-S-O'MR16 (where t is 0 to 2), and -R15-S(0)tN(R14)2 (where t is 1 to 2) where each R'** is rKJependentty hydrogen, alkyl, alkenyl, hatoalkyl, cycloalkyl, cycloalkytalkyl aryl araikyt. heterocyclyl, heterocyctylalkyt, heteroaryl or heteroarytalkyt: each R"£ rs *>dependentty a direct bond or a straight or branched alkytene or akenytene cha*r and eac* R,s is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryf. aralkyi. heterocycsy! ^eterocydytalkyl. heteroaryl or heteroarylalkyl, and where each of the above substrtuents is unsubstituted.
"Ci-Ci2heteroaryT refers to a heteroaryl radcat as aefinec above having one to twelve carbon atoms. The Ci-C12beteroary* group may oe opbonafty substituted as defined above for a heteroaryl group
"Cs-C^heteroaryT refers to a heteroaryl racfcal as aeftned above having five to twelve carbon atoms. The Cs-C^heteroaryl group may be op6ona»y substituted as defined above for a heteroaryl group.
"Heteroarylalkyl" refers to a radical of the formula -R^R* where Ra is an alkyl radical as defined above and Rf is a heteroaryl radical as defined above. The heteroaryl part of the heteroarylalkyl radical may be optionally substituted as defined above for a heteroaryl group. The alkyl part of the heteroarylalkyl radical may be optionally substituted as defined above for an alkyl group.
"C3-Ci2heteroarylalkyl" refers to a heteroarylalkyl radical as defined above having three to twelve carbon atoms. The Cr-C^heteroarytalkyl group may be optionally substituted as defined above for a heteroarytafcy* group.
"Heteroarylcycloalkyl" refers to a radical of the formula -R^Rr where Rd is a cycloalkyl radical as defined above and Rf is a heteroaryl radical as defined above. The cycloalkyl part of the heteroarylcycloalkyl radical may be optionally substituted as defined above for a cycloalkyl group. The heteroaryl part of the heteroarylcycloalkyl radical may be optionally substituted as defined above for a heteroaryl group.
"Heteroarylalkenyl" refers to a radical of the formula -RoR* where Rb is an alkenyl radical as defined above and Rf is a heteroaryl racfcal as defined above. The heteroaryl part of the heteroarylalkenyl radical may be optionally substituted as defined above for a heteroaryl group. The alkenyl part of the heteroarylalkenyl radical may be optionally substituted as defined above for an alkenyl group.
"Hydroxyalkyl" refers to a radical of the formula -R.-OH where Ra is an alkyl radical as defined above. The hydroxy group may be attached to the alkyl radical on any carbon within the alkyl radical. The alkyl part of the hydroxyalkyl group may be optionally substituted as defined above for an alkyl group.

"C2-C12hydroxyalkyr refers to a hydroxyalkyf radical as defined above containing two to twelve carbon atoms. The atkyt part of the Cr-C-2hydroxyaIkyl radical may be optionally substituted as defined above for an alky! group
nC;rC12hydroxyaIkyr refers to a hydroxyalkyf racScaf as defined above containing three to twelve carbon atoms. The alkyl part erf the Cr-C-;>hydroxyaIkyl radical may be optionally substituted as defined above for ar akyi group
"Cr-Ci2hydroxyaIkyr refers to a hydroxyafkyf radca as Defined above containing seven to twelve carbon atoms The alky* parr of the C-C-y^ydroxyalkyl radical may be optionally substituted as defined above tor ar a&ry grouo
"HydroxyalkenyT refers to a radical of the formula -*L-OH vwhere R^ is an alkenyl radical as defined above. The hydroxy group may x aGached to the alkenyl radical on any carbon within the alkenyl radicaL The akeny* sar: zf the hydroxyalkenyl group may be optionally substituted as defined above far ar altenyt group.
MC2-Ci2hydroxyalkenyT refers to a hydroxyalcenyf radicai as defined above containing two to twelve carbon atoms. The alkenyl pat of the Cr-C-^hydroxyalkenyl radical may be optionally substituted as defined above for an akenyl group.
"C3-C12hydroxyalkenyr refers to an hydroxyalkenyl radical as defined above containing three to twelve carbon atoms. The alkenyl part of the C3-C12hydroxyalkenyl radical may be optionally substituted as defined above for an alkenyl group.
"Hydroxyl-d-Ce-alkyl" refers to a radical of the formula -Rh-OH where Rh is an unbranched alkyl radical having one to six carbons and the hydroxy radical is attached to the terminal carbon.
"Trihaloalkyl" refers to an alkyl radical, as defined above, that is substituted by three halo radicals, as defined above, e.g., trifluoromethyl The akyl part of the trihaloalkyl radical may be optionally substituted as defined above for an alkyl group.
"Ci-Cgtrihaloalkyr refers to a trihaloalkyl radicai as defined above having one to six carbon atoms. The CTCetrihaloalkyl may be optionaiy substituted as defined above for a trihaloalkyl group.
"Trihaloalkoxy" refers to a radical of the formula -OR^ where R^ is a trihaloalkyl group as defined above. The trihaloalkyl part of the trihatoakoxy group may be optionally substituted as defined above for a trihaloalkyl group.
"C^Cetrihaloalkoxy" refers to a trihatoakoxy radical as defined above having one to six carbon atoms. The Ci-C6trihatoalkoxy group may be optionally substituted as defined above for a trihaloalkoxy group.
"A multi-ring structure" refers to a multicyclic ring system comprised of two to four rings wherein the rings are independently selected from cycloalkyl, aryl,

heterocyclyl or heteroaryl as defined above. Each cyctoaflcy* may be optionally substituted as defined above for a cyctoattcyt group. Each ary\ may be optionally substituted as defined above for an aryl group. Each heterocydyi may be optionally substituted as defined above for a heterocydyl group Eacfc heteroaryl may be optionally substituted as defined above for a hefceroary* group The nngs may be attached to other through direct bonds or some or afl ctf the nngs may be fused to each other. Examples include, but are not fcmited to a cyctoaiky -adca! substituted by aryl group; a cydoalkyl group substituted by an aryl group ***ct. r tun ES substituted by another aryl group; and so forth.
"Prodrugs" is meant to indicate a compound fat mav be converted under physiological conditions or by sofvotysis to a biotogcaiy ac&ve corcound c^ the invention. Thus, the term "prodrug" refers to a mefcaboic crecxrscr of a compound of the invention that is pharmaceutical^ acceptable. A prodrug may be inactive when administered to a subject in need thereof, but is converted r? *nvc to an active compound of the invention. Prodrugs are typically rapidly transformed r. vrvo to yield the parent compound of the invention, for example, by hydrolysis in blood. The prodrug compound often offers advantages of solubility, tissue compatibility or deteyed release in a mammalian organism (see, Bundgard, H., Design of Prodrugs (1985), pp. 7-9, 21-24 (Elsevier, Amsterdam).
A discussion of prodrugs is provided in Higuchi, T.f et ai, "Pro-drugs as Novel Delivery Systems," A.C.S. Symposium Series, Vol. 14, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated r. fui by reference herein.
The term "prodrug" is also meant to include any covatentiy bonded carriers which release the active compound of the invention in vivo when such prodrug is administered to a mammalian subject. Prodrugs of a compound of the invention may be prepared by modifying functional groups present in the compound of the invention in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound of the invention. Prodrugs include compounds of the invention wherein a hydroxy, amino or mercapto group is bonded to any group that when the prodrug of the compound of the invention is administered to a mammalian subject cleaves to form a free hydroxy, free amino or free mercapto group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol or amine functional groups in the compounds of the invention and the Bee.
"Stable compound" and "stable structure" are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction

mixture, and formulation into an efficacious therapeutic agent.
"Mammal" includes humans and domestic anrnais. such as cats, dogs, swine, cattle, sheep, goats, horses, rabbits, and the fike.
"Optional" or "optionally" means that the subsequently described event of circumstances may or may not occur, and that the description nciudes ^stances where said event or circumstance occurs and instances in which t aoes not For example, "optionally substituted aryT means that the aryl racficai may or may not be substituted and that the description includes both substituted ary racScae anc ar/ rackets having no substitution.
"Pharmaceutical^ acceptable carrier, diuent or eaeperT" roudes without limitation any adjuvant carrier, excipient gfctant, sweetener; agerc Ajem preservative, dye/colorant, flavor enhancer, surfactant vetting agent tfepersng agent suspending agent, stabilizer, isotonic agent solvent or emutsifier whicfc has been approved by the United States Food and Drug Administration as being acceptable for use m humans or domestic animals.
Tharmaceutically acceptable salt" includes both aad and base addition salts.
"Pharmaceutical^ acceptable acid addition safT refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as, but not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric add, phosphoric acid and the like, and organic acids such as, but not limited to, acetic acid, 2.2-dichtoroacetic acid, adipic acid, alginic acid, ascorbic acid, asparfcc acid, benzenesutfbnic acid, benzoic acid, 4-acetamidobenzoic acid, camphoric acid, campboMO-suKonic acid, capric acid, caproic acid, capryiic acid, carbonic acid, cinnamic acid, citric acid, eyjamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydrcKyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-giutaric add. glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic aod. lactobionic acid, taunc acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesutfomc acid, muac acid, naphthalene-1,5-disulfonic acid, naphthalene-2-suffonic acki 1-hydroxy-2~naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic add, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosaficyic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid, undecylenic acid, and the like.
"Pharmaceutical acceptable base addition salt" refers to those salts which retain the biological effectiveness and properties of the free adds, which are not biologically or

otherwise undesirable. These salts are prepared from addition of an riorganic base or an organic base to the free acid. Salts derived from inorganic bases indude. but are not limited to, the sodium, potassium, lithium, ammonium, cataum. magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Preferred inorganc sate are the ammonium, sodium, potassium, calcium, and magnesium safts Salts derived from organic bases include, but are not limited to, salts of primary secondary and tertiary amines, substituted amines including naturafry occurring suDstiuted arranes, cyclic amines and basic ion exchange resins, such as ammona. soproc^arwie trimethytamine, diethyiamine, triethytamne, tnpropytamne ctetTaraarnre ethanolamine, deanol, 2^inr>ethytam!noethanot. 2-yidi'M«JrfhanaL dicyclohexylamine, lysine, arg'mine, histkSne. caffeine, procane ^yarataamrje, choline, betaine, benethamine, benzathine, ethylenediarTMne. gfcjcosarnne me*hy*glucamine, theobromine, triethanolamine, tromethamine, purines, piperazsie. piperidine, A/-ethylpiperidine, polyamine resins and the Bee. Particularly preferred organic bases are isopropylamine, diethyiamine, ethanolamine, trimethytamine, cficydohexytamine, choline and caffeine.
Often crystallizations produce a solvate of the compound of the invention. As used herein, the term "solvate" refers to an aggregate that comprises one or more molecules of a compound of the invention with one or more molecules of solvent. The solvent may be water, in which case the solvate may be a hydrate. Alternatively, the solvent may be an organic solvent. Thus, the compounds of the present invention may exist as a hydrate, including a monohydrate, dihydrate, hemihydrate. sesquihydrate, trihydrate, tetrahydrate and the like, as well as the corresporxing soJvated forms. The compound of the invention may be true solvates, wh&e in other cases, the compound of the invention may merely retain adventitious water or be a mixture of water plus some adventitious solvent.
A "pharmaceutical composition" refers to a formuiabon of a compound of the invention and a medium generally accepted in the art for the de&very of the biologically active compound to mammals, e.g., humans. Such a mecSum includes all pharmaceutical^ acceptable carriers, diluents or excipients therefor.
'Therapeutically effective amount" refers to that amouit of a compound of the invention which, when administered to a mammal, preferably a human, is sufficient to effect treatment, as defined below, of an SCD-mediated disease or condition in the mammal, preferably a human. The amount of a compound of the invention which constitutes a 'therapeutically effective amount" will vary depending on the compound, the condition and its severity, and the age of the mammal to be treated, but can be

determined routinely by one of ordinary skill in the art havng regard to hts own knowledge and to this disclosure.
Treating" or 'treatment" as used herein covers the treatment of the disease or condition of interest in a mammal, preferably a human, having the dsease or disorder of interest, and includes:
(i) preventing the disease or condition from occxrmg r a mammal, in
particular, when such mammal is predisposed to the oxtSbor but has not yet been diagnosed as having it;
(ii) inhibiting the disease or concfiforv i.e.. diiesj^ te devetaoment or
(iii) relieving the disease or coocSton. i e , causrxj 'tayessm of the disease or condition.
As used herein, the terms "disease" and "concfibor" may oe used interchangeably or may be different in that the particular naiady or concfltion may not have a known causative agent (so that ebotogy has not yet been worked out) and it is therefore not yet recognized as a disease but onfy as an tirxtesirabte condition or syndrome, wherein a more or less specific set of symptoms have been identified by clinicians.
The compounds of the invention, or their pharmaceutical^ acceptable salts may contain one or more asymmetric centers and may thus give rise to enantiomers, diastereomers, and other stereoisomers forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)- or, as (D>- or (L>- for amino acids. The present invention is meant to include all such possible isomers, as weB as their racemic and optically pure forms. Optically active (+) and {-;. (Ry and (Sy, or (D)- and (L)- isomers may be prepared using chiral synthons or dhiral reagents, or resolved using conventional techniques, such as HPLC using a chiral coJumn. When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it ts intended that the compounds include both E and Z geometric isomers. Likewise, aD tautomeric forms are also intended to be included.
A "stereoisomer" refers to a compound made up of the same atoms bonded by the same bonds but having different three-dimensional structures, which are not interchangeable. The present invention contemplates various stereoisomers and mixtures thereof and includes "enantiomers", which refers to two stereoisomers whose molecules are nonsuperimposeable mirror images of one another.
A "tautomer" refers to a proton shift from one atom of a molecule to another atom of the same molecule. The present invention includes tautomers of any said

compounds.
The chemical naming protocol and structure diagrams used herein employ and rely the chemical naming features as utilized by Chemdraw version 7.0.1 (available from Cambridgesoft Corp., Cambridge, MA). For complex chemicaJ names employed herein, a substituent group is named before the group to wnicr it attaches. For example, cyclopropylethyf comprises an ethyl backbone wit?" ryooorapy* substituent In chemical structure diagrams, all bonds are identified except for sorr>e carbon atoms which are assumed to be bonded to sufficient hydroger atoms tc corrpiese the valency.
As an example, a compound of formula (V!b). as sef farsh above n the Summary of the Invention, wherein x and y are each 1. R* R- R5. =?* R~ R7a, RB, R83, R9, R9*, R10and R10a are each hydrogen; R2 is 3^4-fhx>ropner>y>prDp^ and R3 is 2-trifluoromethyl phenyl, i.e., a compound of the fofcwing famia'

is named herein as 5-[4-(2-Trifluoromethyi-ben2oyl)«piperazin-1-y!}-pyridine-2-carboxylic acid [3-(4-fIuoro-phenyl)-propyI}-amide.
Certain radical groups of the compounds of the invention are depicted herein as linkages between two parts of the compounds of the inversion. For example, in the following formula (I):'

W is described, for example, as being -C(0)N(R> or -N(R1)C(0)N(R')-; and V is described as -C(O)-. This description is meant to descrfoe a W group attached to the R2 group as follows: R2-C(0)N(R1)- or R2^N(R1)C(0)N(R1K and meant to describe a V group attached to the R3 group as follows; -C(0)R3. In other words, the description of the W and V linkage groups are meant to be read from left to right in view of formula (I)

as depicted above.
Embodiments of the Invention
In one embodiment of the invention, compounds of formate (Da), as set forth above in the Summary of the Invention, are directed to compounds wherein x and y are each 1; R1 is hydrogen or d-Cealkyi; R2 is setected frorr the group consisting of

In another embodiment of the invention, compounds of formula (lib), as set forth above in the Summary of the Invention, are directed to compounds wherein x and y are each 1; R1 is hydrogen or d-C6alkyl; R2is selected from the group consisting of d-Cealkyl, C2-d2aIkenyl, C2-Ci2hydroxyalkyl, CrC12hydroxyalkenyt, d-C6a!koxy, C3-C12alkoxyalkyl, C3-C12cycloalkyI, C4-C12cycloalkylalkylt d-dsaralkyl, C3-Ci2 heterocyclyl, C3-C12heterocyc!ylalkyl, d-Ci2heteroaryI and C3-C12heteroarylalkyl; R3 is phenyl optionally substituted by one or more substituents setected from the group consisting of halo, cyano, nitro, hydroxy, d-Ceaftyl d-Cetrioaioalkyl, d-Cetrihaloalkoxy, d-Cgalkylsulfonyl, -N(R12)2l -00(0^. -C{0)OR'2 and -S(0)2N(Rt2)2; R4, R5 and R6 are each hydrogen; R7, R7a. Ra. R*8. RS. R5*, R10, and R10a are each hydrogen; and each R12 is independently setected from hydrogen, d-C6alkyl, C3-dcycIoaIkyl, aryl oraralkyl.
One embodiment of this embodiment are compounds wherein R2 is C7-C12aralkyl optionally substituted by one or more substituerts setected from the group consisting of halo, Ci-C3alkyl and d-Cetrihaloalkyt and R3 ts phenyl optionally substituted by one or more substituents setected from the group consisting of halo, d-Cealkyl, d-C6trihaloaIkyl and d-Cetrihatoa!koxy.
Another embodiment of this embodiment are compounds wherein R2 is d-C12alkyl or C2-C12alkenyl; and R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, d-Cealkyl, d-C6trihaloalkyl
and d-C6trihaIoalkoxy.
Another embodiment of this embodiment are compounds wherein R2 is

One embodiment of this embodiment are compounds wnerein R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-C6alkyi, Ci-Cstrihatoalkyl. C*-C*trihatoalkoxy, d-Ceaikylsulfonyl, -N(R12)2, -OC(0)R'2, -C(0)OR12. -S(OfcN(R*2fc. cycioaikyt. heterocyclyl, heteroaryl and heteroarylcydoalkyt; and eacf^ n'2 rs ndependentty selected from hydrogen, d-Cealkyl, CrCsCydoaftcyl, aryl or arafcyi
In another embodiment of the invention, compounds d formuia =V). as set forth above in the Summary of the Invention, are (Srected to corTpcxncs inhere*" x and y are each 1; Wa is -N(R1)s Va ts -C(OK R' is hydrogen or C-Cta** ^*s selected from the group consisting of C^-C^kyl CVd^lkenyt. Cr-dahydroavafcy. C2-C12hydroxyalkenyl1 Cr-dzalkoxyalkyl, Cr-drcyctoaic/ Ci-C-^cjcioakytakyl, aryl, C7-C19aralkyl, C3-C12 heterocyclyl, CrC^heterocydytaBcyl. C-C^neaaudiyl and C3-C12heteroarylalkyl; R3 is selected from the group consisting of C—C^afcyf, C2-Ci2alkenyl, Cr-C^hydroxyalkyl, Cs-C^hydroxyalkenyt, Cr-djakoxyakyl, C3-Ci2cycloalkyl, C4-C12cycloalkylalkyl, aryl, d-dsarafkyl, QrC12heteroc>^yl, C3-Ci2heterocyclylalkyl, C^C^heteroaryl and CrC^heteroarytakyt R4, R5 and R6 are each hydrogen; and R7, R7a, R8, R8a, R9, R98, R10, and R10a are each hydrogen.
One embodiment of this embodiment are compounds wherein R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-dalkyl. Ci-C6trihaloalkyl, d-C6trihaIoalkoxy, d-Cealkylsulfonyl, -N(R12)2j -OC(0)R12, -C(0)OR12, -SfO^CR^fc, cycloalkyl, heterocyclyl, heteroaryl and heteroarylcycloalkyi; and each R*2 is independently selected from hydrogen, Ci-C6alkyl, C3-C6cyctoalkyl, aryl or araicyt.
In another embodiment of the invention, compounds of formula (V), as set forth above in the Summary of the Invention, are directed to compounds wherein x and y are each 1; Wa is -S(0)r (where t is 0,1 or 2); Va is -C(OK R2 is selected from the group consisting of d-C^alkyl, Ca-C^alkenyl, C2-d2hydroxyaicyi drdahydroxyalkenyl, C3-Ci2alkoxyalkyl, C3-C12cycloalkyl, C4-C12cyctoalkyta!kyi, aryl C-dgarakyl, C3-C12 heterocyclyl, C3-Ci2heterocyclylalkyl, d-C12heteroaryl and Cr-C-2heteroarytaIkyl; R3 is selected from the group consisting of d-d^kyl, C2-d2aBcenyt Cz-dzhydroxyalkyl, C2-d2hydroxyalkenyl, C2-C12alkoxyalkyl, Cr-djcydoalkyf, Cr-drcyctoalkytalkyl, aryl, C7-C19aralkyl, C3-Ci2heterocyclyl, C3-C12heterocyclytalkyl, d-d2heteroary! and C3-C12heteroarylalkyl; R4, R5 and R6 are each hydrogen; and R\ R7a, Re, R83, R9, R9a, R10, and R10a are each hydrogen.
One embodiment of this embodiment are compounds wherein R3 is phenyl optionally substituted by one or more substituents selected from the group consisting

Another embodiment of this embodiment are compounds wherein R2 is C3-Ci2cycloalkyl or C4-d2cycloalkylaIkyl; and R3 is phenyl optionaBy substituted by one or more substituents selected from the group consisting of hato. C--CsaDcy!. Ct-C6trihaloaIkyI and d-C6trihaloalkoxy.
Another embodiment of this embodiment are compounds where** R~ ts C7-C12aralkyl optionally substituted by one or more substituents setected from the group consisting of halo, d-C3alky1 and Ci-C6trfoataaBcyit and ^ JS naphthyl optionally substituted by one or more substituents setected from the you^ conststng of hate, d-C6aIkyi, d~C6trihaloa!kyt and d-Cetrfoaloalkaxy
Another embodiment of this embodiment are compounds #^^g,e^^' R* ts C3-d2heterocycfylalkyI optionally substituted by one or mar* suosd&jents setected from the group consisting of halo, cyano, nitro. hydroxy. C—daicyl C—Cstnhaloalkyl, d-Cetrihaloalkoxy, d-C6alkylsulfonyl, -N(Rt2)i, -OC(0)R'2. -OOOR*2 or -S(0)2N(R12)2; R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C6a'kyl. d-C6trihak>alkyt and C-Cstrtialoalkoxy; and each R12 is independently selected from hydrogen, d-dafcy(. Cr-C$cycloalkyl, aryl or aralkyl.
One embodiment of this embodiment are compounds wherein R2 is 2-piperazinylethyl optionally substituted by -C(0)OR12.
Specific embodiments of the compounds of the invention are disclosed herein in the following Reaction Schemes and Examples.
In another embodiment, the methods of the invention are directed to methods of treating a disease or condition mediated by stearoyJ-CoA desafcjrase (SCD) in a mammal, wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of formulae (lla). (lib), (III), (IV), (V), (Via) and (Vlb).
In another embodiment of the pharmaceutical compositions of the invention are directed to pharmaceutical compositions comprising a pharmaceuticaiy acceptable excipient and a therapeutically effective amount of a compound of formuiae (ila), (lib), (III), (IV), (V), (Via) and (Vlb).
In another embodiment, the methods of the invention are directed towards the treatment and/or prevention of diseases mediated by stearoyJ-CoA desaturase (SCD), especially human SCD (hSCD), preferably diseases related to dysfipkiemia and disorders of lipid metabolism, and especially a disease related to etevated plasma lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome and the like by administering an effective amount of a compound of the invention.

The present invention also relates to pharmaceutical composition containing the compounds of the invention. In one embodiment, the inventor, relates to a composition comprising compounds of the invention in a pharmaceutical^ acceptable carrier and in an amount effective to modulate triglyceride tevei or to treat diseases related to dyslipidemia and disorders of lipid metabolism, wher administered to an animal, preferably a mammal, most preferably a human patoert In an embodiment of such composition, the patient has an elevated ipid level, sue*- as elevated triglycerides or cholesterol, before administration of said compound of the r^grbon and the compound of the invention is present in an amount effective ID ~eauce sa£ iotd level.
Utility and Testing of the Compounds of the Invention
The present invention relates to compounds, pharmaceu&cal compassions and methods of using the compounds and pharmaceutical composibons for the treatment and/or prevention of diseases mediated by stearoyt-CoA desaturase (SCD). especially human SCD (hSCD), preferably diseases related to dysfipiderrua and disorders of lipid metabolism, and especially a disease related to elevated plasma ipid levels, especially cardiovascular disease, diabetes, obesity, metabolic syndrome and the like, by administering to a patient in need of such treatment an effective amount of an SCD-modulating, especially inhibiting, agent.
In general, the present invention provides a method for treating a patient for, or protecting a patient from developing, a disease related to dyslipidemia and/or a disorder of lipid metabolism, wherein lipid levels in an animaL especsa&y a human being, are outside the normal range (i.e., abnormal lipid level such as elevated plasma lipid levels), especially levels higher than normal, preferably where said lipid is a fatty acid, such as a free or complexed fatty acid, triglycerides, phospholipids, or cholesterol, such as where LDL-cholesterol levels are elevated or HDL-cholesterol levels are reduced, or any combination of these, where said fipid-related condition or disease is an SCD-mediated disease or condition, comprising administering to an animal, such as a mammal, especially a human patient, a therapeutically effective amount of a compound of the invention or a pharmaceutical cotrposition comprising a compound of the invention wherein the compound modulates the activity of SCD, preferably human SCD1.
The compounds of the invention modulate, preferably inhfcit, the activity of human SCD enzymes, especially human SCD1.
The general value of the compounds of the invention in modulating, especially inhibiting, the activity of SCD can be determined using the assay described below in

Example 5. Alternatively, the general value of the compounds m treating disorders and diseases may be established in industry standard animal modeis for ctemoostrating the efficacy of compounds in treating obesity, diabetes or elevated triglyceride or cholesterol levels or for improving glucose tolerance. Such modete include Zucker obese fa/fa rats (available from Harlan Sprague Dawtey Inc ;lndanapofcs Indiana)), or the Zucker diabetic fatty rat (ZDFIGm\CrV-fa/fa) (available teom Znahes River Laboratories (Montreal, Quebec)).
The compounds of the instant invention are inhfoilors c* oete-9 oesarjrases and are useful for treating diseases and disorders in humans anc other organisms, including all those human diseases and disorders which are the r-su* of aberrant delta-9 desaturase biological activity or which may be ameioratec by -roiJaton of delta-9 desaturase biological activity.
As defined herein, an SCD-mediated disease or condter indudes but is not limited to a disease or condition which is, or is related to, cardcvasoiar disease, dyslipidemias (including but not limited to disorders of serum tevete of triglycerides, hypertriglyceridemia, VLDL, HDL, LDL, fatty acid Desaturation index (e.g. the ratio of 18:1/18:0 fatty acids, or other fatty acids, as defined elsewhere herein), cholesterol, and total cholesterol, hypercholesterolemia, as well as cholesterol disorders (including disorders characterized by defective reverse cholesterol transport), familial combined hyperlipidemia, coronary artery disease, atherosclerosis, heart disease, cerebrovascular disease (including but not limited to stroke, ischemic stroke and transient ischemic attack (TIA)), peripheral vascular disease, and ischemic retinopathy. In a preferred embodiment, compounds of the invention wfll, in a patient increase HDL levels and/or decrease triglyceride levels and/or decrease LDL or non-HDL-chotesteroI levels.
An SCD-mediated disease or condition also includes metaboic syndrome (including but not limited to dyslipidemia, obesity and insulin resistance, hypertension, microalbuminemia, hyperuricaemia, and hypercoagulability). Syndrome X. diabetes, insulin resistance, decreased glucose tolerance, non-insulin-dependent diabetes mellitus, Type II diabetes, Type I diabetes, diabetic complications, body weight disorders (including but not limited to obesity, overweight cachexia and anorexia), weight loss, body mass index and leptin related diseases. In a preferred embodiment, compounds of the invention will be used to treat diabetes mellitus and obesity.
As used herein, the term "metabolic syndrome" is a recognized clinical term used to describe a condition comprising combinations of Type II diabetes, impaired glucose tolerance, insulin resistance, hypertension, obesity, increased abdominal girth,

hypertriglyceridemia, low HDL, hyperuricaemia, hypercoaguiaoifity and/or microalbuminemia.
An SCD-mediated disease or condition also includes fatty &ver. hepatic steatosis, hepatitis, non-alcoholic hepatitis, non-alcoholic steatohepatite (NASH). alcoholic hepatitis, acute fatty liver, fatty liver of pregnancy dnjgnnouced hepatitis, erythrohepatic protoporphyria, iron overload disorders, herectary henxchromatosis. hepatic fibrosis, hepatic cirrhosis, hepatoma and conditions r»a»c tfverex:
An SCD-mediated disease or condition afeo tnciudes our s not limteG to a disease or condition which is, or is related to primary hyperthghcanbeoia or hypertriglyceridemia secondary to another disorder or disease suc^ as hyperlipoproteinemias, familial histiocytic reticulosis, fcpoproter lease rtetaency, apolipoprotein deficiency (such as ApoCII deficiency or ApoE ciefiaency). and the Bke, or hypertriglyceridemia of unknown or unspecified etiology
An SCD-mediated disease or condition also includes a efisorder of polyunsaturated fatty acid (PUFA) disorder, or a skin disorder, including but not limited to eczema, acne, psoriasis, keloid scar formation or prevention, diseases related to production or secretions from mucous membranes, such as monounsaturated fatty acids, wax esters, and the like.
An SCD-mediated disease or condition also includes inflammation, sinusitis, asthma, pancreatitis, osteoarthritis, rheumatoid arthritis, cystic fibrosis, and premenstrual syndrome.
An SCD-mediated disease or condition also includes but is not imited to a disease or condition which is, or is related to cancer, neoplasia, rnaignancy. metastases, tumours (benign or malignant), carcinogenesis, hepatomas and the like.
An SCD-mediated disease or condition also includes a condition where increasing lean body mass or lean muscle mass is desred. such as is desirable in enhancing performance through muscle building. Myopathies and ipid myopathies such as carnitine palmitoyltransferase deficiency (CPT I or CPT if) are also included herein. Such treatments are useful in humans and "m animal husbandry, including for administration to bovine, porcine or avian domestic animals ex any other animal to reduce triglyceride production and/or provide leaner meat products and/or healthier animals.
An SCD-mediated disease or condition also includes a disease or condition which is, or is related to, neurological diseases, psychiatric disorders, multiple sclerosis, eye diseases, and immune disorders.
An SCD-mediated disease or condition also includes a disease or condition

which is, or is related to, viral diseases or infections including bat vol limited to all positive strand RNA viruses, coronaviruses, SARS virus. SARS-associated coronavirus, Togaviruses, Picornaviruses, Coxsackievirus. Yetow ^ever virus. Flaviviridae, ALPHAVIRUS (TOGAVIRIDAE) including Rubeia virus. Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan eaunne encephalitis virus, Sindbis virus, Semliki forest virus, Chikungunya virus, Crrfong nyong virus. Ross river virus, Mayaro virus, Alphaviruses; ASTROVIRIDAE rcudrc Astrovrus Human Astroviruses; CALICMRIDAE including Vesicular exanthema ctf sMne VT-JS Norwalk virus, Calicivirus, Bovine calicivirus, Pig cateivirus. Hepatite E CORONA VTRIDAE including Coronavirus, SARS virus, Avian infectious broncftte *TJS 3ov*ie coronavirus, Canine coronavirus, Feline infectious perilonite vrus Hxar coronavirus 299E, Human coronavirus OC43, Murine hepatitis virus. Ponane «*fef:»t diarrhea virus, Porcine hemagglutinating encephalomyelitis vims. Porcine transmissible gastroenteritis virus, Rat coronavirus, Turkey coronavirus. Rabbfc coronavirus. Berne virus, Breda virus; FLAVIVIRIDAE including Hepatitis C virus, West Hie virus. Yellow Fever virus, St. Louis encephalitis virus, Dengue Group, Hepatitis G virus. Japanese B encephalitis virus, Murray Valley encephalitis virus, Central European tick-borne encephalitis virus, Far Eastern tick-borne encephalitis virus, Kyasanur forest virus, Louping ill virus, Powassan virus, Omsk hemorrhagic fever virus, Kumiiinge virus, Absetarov anzalova hypr virus, llheus virus, Rocio encephalitis virus, Langat virus, Pestivirus , Bovine viral diarrhea, Hog cholera virus, Rio Bravo Group. Tyulenry Group, Ntaya Group, Uganda S Group, Modoc Group; PICORNAVlRfDAE including Coxsackie A virus, Rhinovirus, Hepatitis A virus, Encephatomyocanitis virus. Mengovirus, ME virus, Human poliovirus 1, Coxsackie B; POTYV1RIDAE including Potyvirus, Rymovirus, Bymovirus. Additionally it can be a disease or infection caused by or linked to Hepatitis viruses, Hepatitis B virus, Hepatitis C virus, human immunodeficiency virus (HIV) and the like. Treatable viral infections include those where the virus employs an RNA intermediate as part of the repicafive cyde (hepatitis or HIV); additionally it can be a disease or infection caused by or ftnked to RNA negative strand viruses such as influenza and parainfluenza viruses.
The compounds identified in the instant specification inhibit the desaturation of various fatty acids (such as the C9-C10 desaturation of stearoyt-CoA) which is accomplished by delta-9 desaturases, such as stearoyi-CoA desaturase 1 (SCD1). As such these compounds inhibit the formation of various fatty acids and downstream metabolites thereof. This may lead to an accumulation of stearoyl-CoA or palmitoyl-CoA and other upstream precursors of various fatty acids; which may possibly result in

a negative feedback loop causing an overall change in fatty aad metabolism. Any of these consequences may ultimately be responsible for the overaB therapeutic benefit provided by these compounds.
Typically, a successful SCD inhibitory therapeutic agent w* meet some or all of the following criteria. Oral availability should be at or above 20% Animal mode* efficacy is less than about 2 mg/Kg, 1 mg/Kg, or 0.5 mg/Kg and the target human dose is between 50 and 250 mg/70 Kg, although doses outside of thrs range may be acceptable.(Hmg/Kg' means milligrams of compound per kflcgrarr of body mass of the subject to whom it is being administered). The therapeutic moex The identification of compounds of the invention as SCD inhibitors was readily accomplished using the SCD enzyme and microsomal assay procedure described in Brownlie et al, supra. When tested in this assay, compounds of the HTvention had less than 50% remaining SCD activity at 10 pM concentration of the test compound, preferably less than 40% remaining SCD activity at 10 pM concentration of the test compound, more preferably less than 30% remaining SCD activity at 10 pM concentration of the test compound, and even more preferably less than 20% remaining SCD activity at 10 pM concentration of the test compound, thereby demonstrating that the compounds of the invention are potent rnhixtors of SCD activity.
These results provide the basis for analysis of the structure-activity relationship (SAR) between test compounds and SCD. Certain R groups tend to provide more

potent inhibitory compounds. SAR analysis is one of the tools those stalled in the art may now employ to identify preferred embodiments of the compounds of the invention for use as therapeutic agents.
Other methods of testing the compounds disclosed herein are aisc readtfy available to those skilled in the art. Thus, in addition, said corracfcng may be accomplished in vivo. In one such embodiment said contacting r stec \a) s accomplished by administering said chemical agent to an anrrsaf dFfk^ieo «vtfh a triglyceride (TG>- or very low density lipoprotein (VLDt Healed asoroes and subsequently detecting a change in plasma triglyceride level r sae amma* thereby identifying a therapeutic agent useful in treating a triglyceride *T3> ^ very on density lipoprotein (VLDL)-related disorder. In such embodiment tie anrr» r^ay be a human, such as a human patient afflicted with such a disorder and r neec zf u sail mart of said disorder.
In specific embodiments of such in vivo processes, saic change in SCD1 activity in said animal is a decrease in activity, preferably wherein sakj SCD1 modulating agent does not substantially inhibit the biological activity of a detta-5 desaturase, delta-6 desaturase or fatty acid synthetase.
The model systems useful for compound evaluation may include, but are not limited tot the use of liver microsomes, such as from mice that have been maintained on a high carbohydrate diet, or from human donors, including persons suffering from obesity. Immortalized cell lines, such as HepG2 (from human iver), MCF-7 (from human breast cancer) and 3T3-L1 (from mouse adipocytes) may also be used. Primary cell lines, such as mouse primary hepatocytes, are also useful n testing the compounds of the invention. Where whole animate are used, mice used as a source of primary hepatocyte cells may also be used wherein the mice have been maintained on a high carbohydrate diet to increase SCD activity in mirocrosomes and/or to etevate plasma triglyceride levels (i.e., the 18:1/18:0 ratio); alternatively mice on a normal diet or mice with normal triglyceride levels may be used. Mouse modete employing transgenic mice designed for hypertriglyceridemia are also avaiabie as is the mouse phenome database. Rabbits and hamsters are also useful as animal models, especially those expressing CETP (cholesteryl ester transfer protein).
Another suitable method for determining the in vivo efficacy of the compounds of the invention is to indirectly measure their impact on inhibition of SCD enzyme by measuring a subject's Desaturation Index after administration of the compound. "Desaturation Index" as employed in this specification means the ratio of the product over the substrate for the SCD enzyme as measured from a given tissue sample. This

may be calculated using three different equations 18:1n-9/18:C lOtec ac*d over stearic acid); 16:1n-7/16:0 (palmrtoleic acid over palmitic acid); and/or 16:1 n-7 + 18:1rw716:0 (measuring all reaction products of 16:0 desaturation over 16:0 substrate) Desaturation Index is primarily measured in liver or plasma triglycerides but may also be measured in other selected lipid fractions from a variety of fessues Desaturation Index, generally speaking, is a tool for plasma Bpid profffing
A number of human diseases and disorders are the resjjr dt aberrant SCD1 biological activity and may be ameliorated by modulation of SCO" ooogicaf activity using the therapeutic agents of the invention.
Inhibition of SCD expression may also affect the fatty aac ^onpcsibor of membrane phospholipids, as well as production or levels of tngfycendes and. cholesterol esters. The fatty acid composition of phospholipids utrr^tety determines membrane fluidity, while the effects on the composition of triglycerides and chotesterol esters can affect lipoprotein metabolism and adiposity.
In carrying out the procedures of the present invention ft is erf course to be understood that reference to particular buffers, media, reagents, eels, culture conditions and the like are not intended to be limiting, but are to be read so as to include all related materials that one of ordinary skill in the art would recognize as being of interest or value in the particular context in which that discussion is presented. For example, it is often possible to substitute one buffer system or culture medium for another and still achieve similar, if not identical, results. Those of skMI in the art will have sufficient knowledge of such systems and methodologies so as to be able, without undue experimentation, to make such substitutions as wffl optimally serve their purposes in using the methods and procedures disclosed herein-
Pharmaceutical Compositions of the Invention and Administration
The present invention also relates to pharmaceutical composition containing the compounds of the invention disclosed herein. In one embodiment, the present invention relates to a composition comprising compounds of the invention in a pharmaceutically acceptable carrier and in an amount effective to modulate triglyceride level or to treat diseases related to dyslipidemia and disorders of lp*d metabolism, when administered to an animal, preferably a mammal, most preferably a human patient. In an embodiment of such composition, the patient has an elevated lipid level, such as elevated triglycerides or cholesterol, before administration of said compound of the invention and the compound of the invention is present in an amount effective to reduce said lipid level.

The pharmaceutical compositions useful herein also contain a pharmaceutical^ acceptable carrier, including any suitable diluent or excipient which includes any pharmaceutical agent that does not itself induce the production o^ antibodies harmful to the individual receiving the composition, and which may be admrustered without undue toxicity. Pharmaceutical^ acceptable carriers include, but are not Smted to Squids, such as water, saline, glycerol and ethanol, and the Bee. A thorough cfecussior of pharmaceutical^ acceptable carriers, diluents, and other excoents s presented m REMINGTON'S PHARMACEUTICAL SCIENCES fMack Pub Ce \ . current edition).
Those skilled in the art know how to determine suitable aoses a* the compounds for use in treating the diseases and disorders cortenptatec herein. Therapeutic doses are generally identified through a dose ranging study r humans based on preliminary evidence derived from animai studies. Doses must be sufficient to result in a desired therapeutic benefit without causing unwanted side-effects for the patient. The preferred dosage range for an animal is 0.001 mg/Kg to 10.000 mg/Kg, including 0.5 mg/Kg, 1.0 mg/Kg and 2.0 mg/Kg, though doses outside this range may be acceptable. The dosing schedule may be once or twice per day, although more often or less often may be satisfactory.
Those skilled in the art are also familiar with determining administration methods (oral, intravenous, inhalation, sub-cutaneous, etc.), dosage forms, suitable pharmaceutical excipients and other matters relevant to the delivery of the compounds to a subject in need thereof.
In an alternative use of the invention, the compounds of the invention can be used in in vitro or in vivo studies as exemplary agents for comparative purposes to find other compounds also useful in treatment of, or protection from, the various diseases disclosed herein.
Preparation of the Compounds of the Invention
It is understood that in the following description, combinations of substrtuents and/or variables of the depicted formulae are permissible onty if such contributions result in stable compounds.
It will also be appreciated by those skilled in the art that in the process described below the functional groups of intermediate compounds may need to be protected by suitable protecting groups. Such functional groups include hydroxy, amino, mercapto and carboxylic acid. Suitable protecting groups for hydroxy include trialkylsilyl or diarylalkylsilyl (e.g., f-butyldimethylsilyl, f-butyldiphenylsifyl or

trimethylsityl), tetrahydropyranyl, benzyl, and the like. Suitabte protecting groups for amino, amidino and guanidino include f-butoxycarborryl, benzytoxycart>orryt. and the like. Suitable protecting groups for mercapto include -CfOJ-R" (where R* is akyi, aryl or arylalkyl), p-methoxybenzyl, trityl and the like. Suitable protecting groups for carboxylic acid include alkyl, aryl or arylalkyl esters.
Protecting groups may be added or removed in accordance war standard techniques, which are well-known to those skiDed in the art anc as oescribec r>eretn.
The use of protecting groups is descrft>ed in detail n Greer - A arc c G.M. Wutz, Protective Groups in Organic Synthesis (1999). 3rd Ed. Wle* ~*Te protecting group may also be a polymer resin such as a Wang resin or a 2 1
It will also be appreciated by those skiBed in the art aftftougr SJCT protected derivatives of compounds of this invention may not possess pharmacological activity as such, they may be administered to a mammal and thereafter metabolized in the body to form compounds of the invention which are pharmacologically active. Such derivatives may therefore be described as "prodrugs". All prodrugs of compounds of this invention are included within the scope of the invention.
The following Reaction Schemes illustrate methods to make compounds of this invention. It is understood that one of those skilled in the art would be able to make these compounds by similar methods or by methods known to one skilled in the art. In general, starting components may be obtained from sources such as Sigma Aldrich, Lancaster Synthesis, Inc., Maybridge, Matrix Scientific, TCI, aid Ruorochem USA, etc. or synthesized according to sources known to those skilled in the art (see, e.g.. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. 5th edition (Wiley, December 2000)) or prepared as described in this invention. R\ R2. R3, R4, R5, R6, R7, R7a, R8, R8a, R9, R9a, R10, R10a and V are defined as in the Specification unless specifically defined otherwise. X is selected from CI or Br. PG represents a protecting group such as BOC, benzyl group and the like.
In general, the compounds of formula (I) of the invention where W is -C(0)N(R1)- and V is -C(O)-, -S(0)r or -C(R11)H- can be synthesized following the general procedure as described in Reaction Scheme 1.

equivalent) in a solvent, such as dichloromethane, chloroform or toluene, but not limited to, at 0°C in the presence of a base such as diisopropytethytamme. is added a solution of a compound of formula 102 (1 equivalent). The resulting mixture is stirred at ambient temperature for 8 - 24 h. The reaction ts quenched witr wafer The organic phase is washed with water, dried over a drying agent such as anhydrous Na-SO*. filtered and concentrated in vacuo to yield compound (103).
Compound (104): A solution of compound of formula of (1C3) aotamec above is dissolved in an adequate solvent and the protection group PG s nenwed under standard deprotection conditions such as hydrolysis or hydrogenatar i: otter: the amine of formula (104).
Compound (107): To a solution of 54Tydroxypyridne-2-caocaryic aad * equivalent) in a solvent such as dichloromethane, chloroform ortoiuene s added a base such as triethylamine, diisopropylethylamine, foflowed by l-hydnxybenzotriazote monohydrate (1 equivalent) and a coupling agent (1 equivalent) suc^ as EDCl. The resulting mixture is stirred for 15 - 60 min and the amine of formica (106) (1 equivalent) is added. After stirring for 18 - 24 hours, the reaction mixture is diluted with dichloromethane, washed with water, dried over anhydrous Na2S04, filtered and concentrated in vacuo. Purification by flash chromatography yields compound (107).
Compound (108): To a solution of compound of formula (107) obtained above (1 equivalent) at 0°C in a solvent such as dichloromethane is added triethylamine (1.5 to 2.5 equivalent) followed by dropwise addition of a solution of trifluoromethanesulfonic anhydride (1.1 to 1.5 equivalent) in a solvent such as dichloromethane. The resulting mixture is stirred at 0°C for 3 - 8 h and then quenched with water. The organic layer is separated, dried over anhydrous MgSO*. filtered and concentrated in vacuo. Purification by flash column chromatography affords compound (108).
Compound of Formula (I): This compound is obtained using BuchwaW reaction. In general, a flask under argon atmosphere is charged with a base such as cesium carbonate or potassium carbonate, palladium catalyst such as palladium diacetate and a ligand such as BINAP. A solution of compound (108) and compound (104) in toluene is added via syringe. The reaction mixture is then heated at 100°C for 26 h, cooled to ambient temperature, diluted with toluene, filtered and concentrated in vacuo. The crude product was purified via flash column chromatography affords compound of Formula (I).
Alternatively, the compounds of formula (I) of the invention where W is -C(0)NH- and V is -C(O)-, -S(0)2- or -C(R11)H- can be synthesized following the

the above reaction scheme as follows:
Compound 116. To a stirred solution of the amine of formula (114) (1 equivalent) in a solvent such as dichloromethane or toluene is added the solution of a chloride of formula (115) (1 equivalent) in a solvent such as dichtoromethane or toluene in the presence of a base such as triethylamine or Hunigs tjase The resulting mixture is stirred at ambient temperature for an adequate time penod and then quenched with water. The organic phase is washed with H70. fame dned over and then concentrated in vacuo to afford the product of formula (116)
Compound 117. A solution of compound of formula of (116) oexaned aoove is dissolved in an adequate solvent and the protection group PG is remote unoer standard deprotection conditions such as hydrolysis or hydrogenabor t obtain the amine of formula (117).
Compound 119. The mixture of a pyridine compound of fbrmusa (117) (1 equivalent) and the compound of formula (118) (1.5 equivalent) in an adequate solvent is heated at reflux for 4-24 hours. To the reaction mixture is added a basic solution such as NaOH solution. The aqueous layer is extracted by an organic solvent such as dichloromethane or ethyl acetate. The combined organic phase is dried, then evaporated to dryness. The crude compound is purified by column chromatography or crystallization to afford the compound of formula (119).
Compound 120. The nitro compound of formula (119) can be reduced to the corresponding amine compound of formula (120) using a standard hydrogenation process known to one skilled in the art.
Compound of formula (I):
Method A: To a stirred solution of compound of formula (120) (1 equivalent) in a solvent such as dichloromethane, acetonitrile or toluene is added the solution of a compound of formula (121) (1 equivalent) in the presence of a base such as triethylamine or Hunigs base (1 equivalent) at 0°C. The resulting mature is stirred at ambient temperature for 8-24 hours and then quenched with water. The organic phase is washed with H20, brine, dried and then concentrated in vacuo to.afford the compound of formula (I) where W is -C(0)NH- and V is -C(0}-, -S(0)r- or -C(R')H-.
Method B: To a solution of the compound of formula (122) (1 equivalent) in a solvent such as dichloromethane, toluene or THF is added a base such as triethylamine or Hunigs base (2.5 equivalent), followed by the addition of a coupling agent such as (3-dimethylaminopropyl)ethyl carbodiimide (1.1 equivalent). The resulting mixture is stirred for 15 minutes to an hour and an amine of formula (120) (1.1 equivalent) is added. The mixture is stirred at ambient temperature for 8-24 hours,

then washed with water, dried and concentrated in vacuo. Purification by column chromatography or crystallization from a suitable solvent affords the compound of formula (I) where W is -C(0)NH- and V is -0(0)-, -S(0)r or -C(FT)B-
Alternatively, the compounds of formula (I) of the invention where W s -NHC(0)NH- and V is -0(0)-, -S(0)z- or -C(R11)H- can be synthesized fotowing the general procedure as described in Reaction Scheme 3.
REACTION SCHEME 3

Formula (I)
The starting materials for the above reaction scheme are commercially available or can be prepared according to methods known to one skSed in the art or by methods disclosed herein. In general, the compounds of the invention are prepared in the above reaction scheme as follows:
Compound of formula (I). To a stirred solution of the compound of formula (120) (1 equivalent) in an anhydrous solvent such as dimethytformamide is added an isocyanate of formula (123) (3 equivalent), and the mixture is then heated to 60 - 80°C for 4 -24 hours. The mixture is concentrated in vacuo. Purification of the crude product by column chromatography or crystallization from a suitable solvent affords the compound of formula (I) where W is -NHC(0)NH- and V is -C(O)-, -S(0)r or -C(R11)H-.
Alternatively, the compounds of formula (I) of the invention where W is

-S(0)2NH- and V is -0(0)-, -S(0)2- or -C(R11)H- can be synthesized fotowmg the general procedure as described in Reaction Scheme 4.
REACTION SCHEME 4

Formula (I)
The starting materials for the above reaction scheme are commerciafly available or can be prepared according to methods known to one staled rt the art or by methods disclosed herein. In general, the compounds of the invention are prepared in the above reaction scheme as follows:
Compound of formula (I): To a solution of compound of formula (118) (1 equivalent) in a solvent such as dichloromethane, acetonrtrite or toluene is added slowly the solution of compound of formula (124) (1 equivalent) at 0*C- The resulting mixture is stirred at ambient temperature for 8-24 hours and then quenched with water. After removal of solvent, the product was purified by chromatography to afford the compound of formula (I) where W is -S(0)2NH- and V is -0(0)-, -S(0)2- or -C(R11)H-.
PREPARATION 1 SYNTHESIS OF PIPERAZIN-1-YL-(2-TRIFLUOROMETHYLPHENYL)METHANONE A. To a stirred solution of 1-Boc-piperazine (0.50 g, 2.7 mmol) and

diisopropylethylamine (1.75 g, 13.5 mmol) in dichloromethane at 0*C was added a solution of 2-trifluoromethylbenzoyl chloride (0.626 g, 3.0 mmol). The resulting mbcture was stirred at room temperature for 20 h and then quenched with water (25 mL). The organic phase was washed with water, dried over anhydrous NajSO*. fiftered and concentrated in vacuo to yield 4-(2-trifluoromethyIberuoyl)p«perazrTe-i B. A solution of 4^2-trifluoromethylbenzoyr)Qiperazre-*H3rtx3fyfc aad ferf-butyl ester (0.948 g, 2.65 mmol) in 50 mL of a 1:4 mixture of trftjor^acebc aoc anddichloromethane was stirred at room temperature for 20 h. After concentrator *i vacuo, the residue was dissolved in dichloromethane (100 mL) and wa&ncd **?* * N NaOH (10 mL), water (15 mL), and brine (15 mL). The organic phase was dned over anhydrous Na2S04, filtered and concentrated in vacuo to yiekj the tide compound as a light brown oil (0.657 g, 2.54 mmol). 1H NMR (300 MHz, CDCy 5 7.69 7.54. 7.30. 3.78, 3.15, 2.94, 2.76. MS (ES+) mfr 259.3 (M+1).
PREPARATION 2
SYNTHESIS OF TRIFLUOROMETHANESULFONIC ACID 6-(3-
PHENYLPROPYLCARBAMOYL)PYRIDIN-3-YL ESTER
A. To a solution of 5-hydroxypyridine-2-carboxylic acid (0.103 g, 0.74
mmol) in dichloromethane was added diisopropylethylamine (0.279 mL 1.6 mmol),
followed by 1-hydroxybenzotriazole monohydrate (0.012 g, 0.8 mmoQ and EDCI (0.153
g, 0.8 mmol). The resulting mixture was stirred for 15 minutes and 3-phenyM-
propylamine (0.108 g, 0.8 mmol) was added. After stirring for 22 h. the reaction
mixture was diluted with dichloromethane (80 mL), washed with water, dried over
anhydrous Na2S04and concentrated in vacuo. Purification by column chromatography
afforded 5-hydroxypyridine-2-carboxylic acid (3-phenylpropyf)amkie as white crystals
(0.116 g, 61% yield). MS (ES+) nVz 257.2 (M+1).
B. To a solution of 5-hydroxypyridine-2-carboxyiic acid (3-
phenylpropyl)amide obtained above (0.097 g, 0.378 mmol) at 0°C in efichtoromethane
(5 mL) was added triethylamine (0.079 mL, 0.567 mmol) followed by dropwise addition
of a solution of trifluoromethanesulfonic anhydride (0.077 mL, 0.454 mmol) in
dichloromethane (2 mL). The mixture was stirred at 0°C for 5 h and quenched with
water (25 mL). The organic phase was separated, dried over anhydrous MgS04,
filtered and concentrated in vacuo. The residue was purified by column
chromatography and the title compounds was obtained as a clear oil (0.124 g, 84%

EXAMPLE 2 SYNTHESIS OF 4-PHENYL-/V-{5-[4-(2-TRIFLUOROMETHYLBENZOYL>PiPERAZIN-
1-YL]-PYRIDlN-2-YL}BUTYRAMIDE To a solution of [4-(6-aminopyridin-3-yI)pipera2irM-^^ methanone (0.035 g, 0.10 mmol) in dichloromethane was added diisopropytethylamine (0.084 ml_, 0.48 mmol), followed by 1-hydroxybenzotriazole monohydrate (0.018 g, 0.12 mmol), EDCI (0.023 g, 0.12 mmol) and DMAP (0.015 g, 0.12 mmol). The resulting mixture was stirred for 15 minutes and 3-phenyl-1-propylamine (0.020 g, 0.12 mmol) was added. After stirring for 18 h, the reaction mixture was diluted with ethyl acetate, washed with brine, dried over anhydrous MgS04, filtered and concentrated in vacuo. Purification by preparative thin layer chromatography afforded the titte compound as a pale white solid (6.2 mg, 12.5% yield). 1H NMR (300 MHz, CDCfe) 5 8.12. 7.97. 7.87. 7.72, 7.59, 7.34, 7.10-7.29, 3.98, 3.34, 3.22, 3.02, 2.70, 2.37, 2.08. MS (ES+) m/z 497.2 (M+1).
EXAMPLE 2.1 The following compounds were synthesized by the similar procedure as described in Example 2:

EXAMPLE 4 SYNTHESIS OF HEXANE-1-SULFONIC ACID {5-[4^2-TR!FLUOROMETHYLBENZOYL)-PIPERAZlN-1-YL]PYRIDIN-2-YL}AMlDE To a solution of [4-(6-aminopyridin-3-yi)piperazin-1-yIH^ methanone (0.035 g, 0.10 mmol) in pyridine (3 ml_) was added hexanesutfonyi chloride (0.022 mL? 0.12 mmol). After heating at 60°C for 20 h, the mixture was cSuted with ethyl acetate (100 ml_), washed with brine, dried over anhydrous MgSO* and concentrated in vacuo. Purification by preparative thin layer chromatography afforded the title compound as a white solid (3.8 mg, 8% yield). 1H NMR (300 MHz. CDCfe) 5 7.66, 7.29, 4.08, 3.91, 3.38, 3.27, 3.08,1.84, 1.35,1.27, 0.87. MS (ES+) m EXAMPLE 4.1 The following compounds were synthesized by the similar procedure as described in Example 4:
Pentane-1 -sulfonic acid {5-[4-(2-trifluoromethylbenzoyl)piperazin-1-yI]pyridin-2-

3-Phenylpropane-1 -sulfonic acid {5-[4^2-trifluoromethylbenzoy1>operazin-1-y!]pyridin-2-yI}amide.
EXAMPLE 5
MEASURING STEAROYL-COA DESATURASE INHIBITION ACTIVE ZF * TES'
COMPOUND USING MOUSE LIVER MICROSOMES
The identification of compounds of the invention as SCD inhfcrtors was readiy
accomplished using the SCD enzymes and microsomal assay procedu* flescrfeog ir.
Brownlie et a/, PCT published patent application, WO 01/62954.
Preparation of Mouse Liver Microsomes:
Male ICR mice, on a high-carbohydrate, low fat diet under Bght hatohane (15% in mineral oil) anesthesia are sacrificed by exsanguination during periods of high enzyme activity. Livers are immediately rinsed with cold 0.9% NaCI solution, weighed and minced with scissors. All procedures are performed at4°C unless specified otherwise. Livers are homogenized in a solution (1:3 w/v) containing 0.25 M sucrose, 62 mM potassium phosphate buffer (pH 7.0), 0.15 M KCI, 1.5 mM /V-acetyleysteine, 5 mM MgCI2, and 0.1 mM EDTA using 4 strokes of a Potter-Efvehjem tissue homogenizer. The homogenate is centrifuged at 10,400 x g for 20 mm to eiminate mitochondria and cellular debris. The supernatant is filtered through a 3-iayer cheesecloth and centrifuged at 105,000 x g for 60 min. The microsomal petet is gentiy resuspended in the same homogenization solution with a small glass/teflon homogenizer and stored at -70°C. The absence of mitochondrial contamination is enzymatically assessed. The protein concentration is measured using bovine serum albumin as the standard.
Incubation of Mouse Liver Microsomes with Test Compounds:
Reactions are started by adding 2 mg of microsomal protein to pre-incubated tubes containing 0.20 nCi of the substrate fatty acid (1-14C palmitic acid) aa a final concentration of 33.3 p.M in 1.5 ml of homogenization solution, containing 42 mM NaF, 0.33 mM niacinamide, 1.6 mM ATP, 1.0 mM NADH, 0.1 mM coenzyme A and a 10 \iM concentration of test compound. The tubes are vortexed vigorously and after 15 min

incubation in a shaking water bath (37°C), the reactions are stopped and fatty acids are analyzed.
Fatty acids are analyzed as follows: The reaction mixture is saponified with 10% KOH to obtain free fatty acids which are further methylated using 3F? r. methanol. The fatty acid methyl esters are analyzed by high performance liquid arornaEDgraphy (HPLC) using a Hewlett Packard 1090, Series II chromatograph eqtrippec wtfr a 3jode array detector set at 205 nm, a radioisotope detector (Mode* 171, Becianar; CA, wrtr 3 solid scintillation cartridge (97% efficiency for ^C-detecfon) and a reverse-prase DDS (C-18) Beckman column (250 mm x 4.6 mm i.d.; 5 pjn partcte size) d*Uu'*ec to a are-column with a fjBondapak C-18 (Beckman) insert Fatty acid methyt esters are separated isocratically with acetonrtrite/water (95:5 vrv) at a flow rate erf * mL/mr anc are identified by comparison with authentic standards. Alternatively fatty add me&V esters may be analyzed by capillary column gas-chromatograpfty (GC) or Thin Layer Chromatography (TLC).
Those skilled in the art are aware of a variety of modifications to this assay that can be useful for measuring inhibition of stearoyl-CoA desaturase activity in microsomes by test compounds.
Representative compounds of the invention showed activity as inhibitors of SCD when tested in this assay. The activity was defined in terms of % SCD enzyme
activity remaining at the desired concentration of the test compound.
*****
All of the U.S. patents, U.S. patent application publications, U.S. paient applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference, in their entirety.
From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of iBusiration. various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims

WHAT IS CLAIMED IS
1. A method of inhibiting human stearoyf-CoA desaturase (hSCD) activity comprising contacting a source of hSCD with a compound of formula (!)

wherein:
x and y are each independently 1, 2 or 3:
W is -O-, -N(R1h -C(Oh -S(0)r; (where t is 0,1 or2). -N(R*;S/0>^. -S(0)2N(R1)-, -OS(0)2N(R1)-, -C(0)N(R1K -OC(0)N(R>, -C(S)N(R>, ^>C{S>*(RV. -N(R1)C(0)- or -N(R1)C(0)N(R1)-;
V is -C(O)-, -C(S)-, -C(0)N(R1)-, -C(0)0-, -S(0)2~, -S(OhN(R> or -C(R11)H-;
each R1 is independently selected from the group consisting of hydrogen, d-C12alkyI, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyf and Cr-CioaraJkyl;
R2 is selected from the group consisting of CrC^alkyl, C2-Ci2alkenyl, C2-Ci2hydroxyalkylt C2-C12hydroxyalkenyl, C2-C12alkoxyaikyI, C3-Ci2cydo^kyi. C4-C12cycloaikyIalkyl, aryl, Cy-dgaralkyl, C3-Ci2heterocydyi, C3-C12heterocyc)yiaJkyl. Ci-C12heteroaryl, and C3-C12heteroarylaIkyl;
or R2 is a mufti-ring structure having 2 to 4 rings whereri the rings are independently selected from the group consisting of cyctoalkyl, heterocydyl. aryl and heteroaryl and where some or all of the rings may be fused to each other
R3 is selected from the group consisting of (VC,2alkyl. Cr-C-^cenyi. C2-C12hydroxyalkyI, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl. Cr-Circyctoaicyl C4-C12cycIoalkylaIkyl, aryl, C7-Ci9aralkyl, C3-C12heterocycfyl, C^^heterocydylalkyt CrC12heteroaryl and C3-C12heteroarylalkyl;
or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cyctoalkyl, heterocyctyi. aryl and heteroaryl and where some or all of the rings may be fused to each other;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or-N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10 and R10a are each independently selected

5. The method of Claim 4 wherein the disease or condition is Type I!
diabetes.
6. The method of Claim 4 wherein the disease or condition is obesity.
7. The method of Claim 4 wherein the disease or condition s *netaboic
syndrome.
8. The method of Claim 4 wherein the disease or condition s fatty wwr
9. The method of Claim 4 wherein the disease or concfitior is nor-aicanoic
steatohepatitis.
10. A compound of formula (Ha):

C3-C12heterocyclylalkyl, d-Ci2 heteroaryl and C3-C12heteroarytaikyi;
R4, R5 and R6 are each independently selected from hydrogen, ftuoro. chloro, methyl, methoxy, trifluoromethyl, cyano, nltro or-N(R'3)i:
R7, R7a, RB, RBa, R9, R93, R10, and R10a are each independently selected from hydrogen or d-C3alkyl;
or R9and R93 together, or R10 and R10a together form an cxc OTDUC *hie the remaining R7, R7a, R8, R83, R9, R93, R10, and R10a are each independency saectec from hydrogen or CVCaalkyi;
or one of R7, R7a, R10 and R10a, together with one of R*P R^ =^and=^ form an alkylene bridge, while the remaining Rt0, R10a. R\ FT*. R*, R** R* anc R* are each independently selected from hydrogen or d-Caalkyt. and
each R13 is independently selected from hydrogen or C-C-afcyt
a stereoisomer, enantiomer or tautomer thereof, a pharmaceLfca*y acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof
11. The compound of Claim 10 wherein:
x and y are each 1;
R1 is hydrogen or d-Cealkyl;
R2 is selected from the group consisting of Cr-C^alky!, C3-C-2alkenyl C7-Ci2hydroxyalkyl, C2-C12alkoxyalkyl, C3-Ci2hydroxyalkenyI, C3-C12cycloafkyi, C4-Ci2cycloalkyIalkyl, C13-Ci9aralkyl, C3-C12heterocyclylalkyl, and C3-Ci2hetero^ylalkyl:
R3 is selected from the group consisting of Cr-d^ky!* d-C-^aicenyi. C3-C12hydroxyaIkyl, C3-C12hydroxyalkenyl, C3-C12atkoxy, d-Ci^koxya&y*. C3-d2cycloalkyl, d-C^cycloalkylalkyl, aryl, Cy-C^aralkyl, C^-Ciiheterocfdtyi. C3-Ci2heterocyclylalkyl, d-Ci2 heteroaryl and C3-C12heteroarylalkyl;
R4, R5 and R6 are each hydrogen; and
R7, R7a, R8, R8a, R9, R93, R10, and R10a are each hydrogen.
12. A method of treating a disease or condition mediated by stearoyi-CoA desaturase (SCD) in a mammal, wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of Claim 10.
13. A pharmaceutical composition comprising a pharmaceutical^ acceptable excipient and a therapeutically effective amount of a compound of Claim 10.

14. A compound of formula (lib):

wherein:
x and y are each independently 1, 2 or 3:
R1 is selected from the group consisting erf hydrogen. C—C«jafcy-C2-C12hydroxyaIkyl, C4-C12cycloalkylalkyt and Cr-Cigaraflcyi,
R2 is selected from the group consisting of Ct-C12aflcyf, Cx-C^^afcenyt C2-C12hydroxyalkyI, C2-C12hydroxyalkenyl, d-Cealkoxy, C3-Ci2aIkoxyalkyi_ C3-Ci2cycloalkyl, C4-Ci2cycloalkylalkyl, Cr-Cigaralkyi, C^-C-.z heterocydyl. C3-C12heterocyclylalkyl, Ci-Ci2heteroaryl and C3-Ci2heteroary!alkyI;
or R2 is phenyl optionally substituted with one or more substituents selected from halo and CrC6trihaloalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocydyl, aryl and heteroaryl, where some or all of the rings may be fused to each other;
R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, Ci-Cealtyl Ci-C$irihaiaaBcytT Ci-C6trihaloalkoxy, d-CealkylsuIfonyl, -N(R12)2, -OC(0)R12, -C(0)OR12, -Sp^R"2)* cycloalkyl, heterocydyl, heteroaryl and heteroarylcycloalkyl, provided that R3 Js not phenyl substituted with optionally substituted thienyl;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or-N(R13)2;
R7, R7a, R8, R8a, R9, R93, R10, and R10a are each independently setected from hydrogen or C^Caalkyl;
or R9and R9a together, or R10 and R10a together form an oxo group, while the remaining R7, R7a, R8, R83, R9, R9a, R10, and R10a are each independently selected from hydrogen or d-C3alkyl;
or one of R7, R7a, R10 and R10a, together with one of R8, R83, Rs and R93, form an alkylene bridge, while the remaining R10, R10a, R7, R7a, R8, R83, R9, and R93 are each independently selected from hydrogen or Ci-C3alkyl; and

each R12 is independently selected from hydrogen. d-daky*. C3-C6cycloalkyl, aryl or aralkyl; and
each R13 is independently selected from hydrogen or d-da§cyt;
a stereoisomer, enantiomer or tautomer thereof, a pharmacsutica&y acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof
15. The compound of Claim 14 wherein:
x and y are each 1;
R1 is hydrogen or Ci-C6aBcyl;
R2 is selected from the group consisting of C-C-jalkyi. Cr-C-rafceny* C2-Ci2hydroxyalkylf d-C^hydroxyalkenyf, C:-C5a!koxy, d-C^aJkoxyaicy C3-Ci2cycloalkyl, d-C^cycloalkylalkyl, Cr-dgaralky!, d-C-2 helerocydyt, C3-d2heterocycIylaIkyl, d-C12heteroaryt and C3-d2heteroarytaky{;
or R2 is phenyl optionally substituted with one or more subsftuerte selected from halo and Ci-C6trihaloalkyl;
R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-dalkyl, d-Cetrihaloaflcyl, d-Cetrihaloalkoxy, d-C6alkylsulfonyIf -N(R12)2, -OC(0)R12, -C(0)OR12 and -S(0)2N(R12)2;
R4, R5 and R6 are each hydrogen;
R7, R7a, R8, R8a, R9f R9a, R10, and R10a are each hydrogen; and
each R12 is independently selected from hydrogen, d-C$akyL d-dcycloalkyl, aryl or aralkyl.
16. The compound of Claim 15 wherein:
R2 is C7-C12aralkyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C3alkyl and d-dtrihatoafcyt and
R3 is phenyl optionally substituted by one or more substituents setected from the group consisting of halo, d-C6alkyl, d-C6trihaloalkyl and d-dtrfraioalkoxy.
17. The compound of Claim 16 selected from the group consistng of the
following:
3-(4-Fluoro-phenyI)-N^5-[4-(2-trifluorom
propionamide; 4-Phenyl-N^5-[4-(2-trifluoromethyl-benzoy!)^^ 4-(4-Fluoro-phenyI)-N^5-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-pyridin-2-yl)-

butyramide; and ^Phenyl-N^544-(2-trifluoromethy^benzoyO
18. The compound of Claim 15 wherein:
R2 is Ci-Ci2alkyl or C2-C12alkenyl; and
R3 is phenyl optionally substituted by one or more substituents seteasd from the group consisting of halo, d-C6alkyl d-C6trihaloaIkyf and d-CstnhaKsafcory
19. The compound of Claim 18 setected from the group consistent of !he
following:
Hexanoic acid {5-[4-(24rifluoromethyt4>enzoyl}-piperaa^
Heptanoic acid {5-[4-(2-trifluoromethyt-benzoyl)-pipe^ and
5-Methylpentanoic acid {5-[4-(24rifluoromethyl-benzoyi)-piperazirh^ amide.
20. The compound of Claim 15 wherein:
R2 is C3-Ci2heteroarylalkyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C3alkyl and d-Cetrihaloalkyl; and
R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C6alkyl, CrC6trihaloalkyl and d-Cetrihaloalkoxy.
21. The compound of Claim 20, namely, 3-Pyridin-3-yl-N-{5^4-{2-trifluoromethyl-benzoyl)-piperazin-1-yl]-pyridin-2-y[}-propionamide.
22. The compound of Claim 15 wherein:
R2 is phenyl optionally substituted with one or more substituerts selected from halo and CrC6trihaloalkyl; and
R3 is phenyl optionally substituted by one or more substituents setected from the group consisting of halo, d-C6alkyl, d-C6trihaloalkyl and C1-CetrtialoaBcoxy.
23. The compound of Claim 22, namely, 4-Fluoro-N-{5-{4-(2-trifluoromethylben2oyl)piperazin-1-yl]pyridin-2-yI}benzamide.
24. A method of treating a disease or condition mediated by stearoyl-CoA desaturase (SCD) in a mammal, wherein the method comprises administering to a

29. The compound of Claim 28 wherein:
R2 is Ci-C12alkyl or C2-Ci2alkenyl; and
R3 is phenyl optionally substituted by one or more substituents seiected from the group consisting of halo, Ci-C6alkyl, Ci-C6trihaloalkyi and C--C^tnhajoafitoxy
30. The compound of Claim 29 selected from the group consisting dt rne
following:
Pentane-1-sulfonic acid {5-[4-(2-trifluoromethyi-benzoyt)^^
amide; and Hexane-1-sulfonic acid {5-[4-(2-trifluoromethyUbenzoy1)-p^
amide.
31. The compound of Claim 28 wherein:
R2 is C7-C12aralkyl optionally substituted by one or more subsftue^rts selected from the group consisting of halo, d-C3aIkyi and Ci-C5trihaloalkyl: and
R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, d-Cealkyl, CTCetrihaloalkyl and Ci-Cstrihatoaftcoxy.
32. The compound of Claim 31, namely, 3-Phenyl-propane-1-sulfonic acid {5-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-pyridin-2-yl}-amide.
33. A method of treating a disease or condition mediated by stearoyt-CoA desaturase (SCD) in a mammal, wherein the method comprises administer**; to a mammal in need thereof a therapeutically effective amount of a compound of Claim 26.
34. A pharmaceutical composition comprising a pharmaceutica&y acceptable excipient and a therapeutically effective amount of a compound of Oaken 26.
35. A compound of formula (IV):

wherein:
x and y are each independently 1, 2 or 3:
Va is -C(O)-, -C(S)-, -C(0)N(RV. -C(0>0-, -S(Oh- or -$(0)-N{=>" -
each R1 is independently selected from the group consist*^ cf hydrogen, C^-C^alky!, C^C^hydroxyalkyl, C4-C12cyctoalkytaflcyl and Cr-C-sarafcy?
R2 is selected from the group consisting of C1-Ci2a&yl, Cr-C-2akerryl. C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl1 C3-C12alkoxyalkyl, Cr-Ci2cyctoafcyytafcyt. Ci-Ci2heteroaryl and C3-C12heteroarylalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other,
R3 is selected from the group consisting of C^C^alkyl, C2-C12alkenyi, C2-Ci2hydroxyalkyl, C2-Ci2hydroxyalkenyl, C2-C12alkoxyalkyl, C3-Ci2cyctoalkyL C4-Ci2cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyI, C;rC12heterocyc*ytaIlcyi. Ci-Ci2heteroaryl and C3-C12heteroarylalkyl;
or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, ary! and heteroaryl and where some or all of the rings may be fused to each other
R4, R5 and R6 are each independently selected from hydrogen, fluoro. chloro, methyl, methoxy, trifluoromethyl, cyano, n'rtroor-N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently setecied from hydrogen orCi-C3alkyl;
or R7 and R7a together, or R8and R8a together, or R9and R9* together, or R10 and R10a together are an oxo group, provided that when Va is -C(O)-, R7and R7a together or R8 and R8a together do not form an oxo group, while the remaining R7, R7i, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or CrC3aikyl;
or one of R10, R10a, R7, and R7a together with one of R8, R8*, R9 and R93

form an alkylene bridge, while the remaining R10, R10at R7, R7a, R8. Rtat Rs. and R* are each independently selected from hydrogen or Ci-C3alkyi; and
each R13 is independently selected from hydrogen or C—Ceaficy4;
a stereoisomer, enantiomer or tautomer thereof, a pharmaceuteafry acceptable salt thereof, a pharmaceutical composition thereof or a prodrug tr>ereof
36. The compound of Claim 35 wherein:
x and y are each 1;
Va is -C(O)-;
each R1 is independently hydrogen or d-Ceakyt: R2 is selected from the group consisting of C-d^alcyl. Cr-C-7a*kery. C2-C12hydroxyalkyl, C^C^hydroxyalkenyl, C;rd2aikoxyalkyf. Cr-d2cyc*oa*y C4-Ci2cycloalkylalkyl, aryl, Cr-dsaralkyl, C3-C12 heterocycty!, CrCi2heterocycMattcyl. d-C12heteroaryl and C3-C12heteroarylaIkyl;
R3 is selected from the group consisting of C1-C12alkyl, C2-C^2^kenyl C2-C12hydroxyaIkyl, C2-C12hydroxyalkenyl, C2-Ci2alkoxyalkyl, C3-d2cyctoaIkyi, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyI, C3-C12heterocyctytalkyi. C-i-C12heteroaryl and C3-C12heteroarylalkyl;
R4, R5 and R6 are each hydrogen; and
R7, R7a, RB, R8a, R9, R9a, R10, and R10a are each hydrogen.
37. The compound of Claim 36 wherein:
R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-C&alkyl, d-CetrihaJoaBcyl d-Cetrihaloalkoxy, d-C6alkylsulfonyl, -N(R12)2l -OC(0)R12, -C(0)OR12, -S(ObN(R'%. cycloalkyl, heterocyclyl, heteroaryl and heteroarylcycloalkyl; and
each R12 is independently selected from hydrogen, d-daHcy*. C3-C6cycloalkylf aryl or aralkyl.
38. The compound of Claim 37 wherein:
R2 is d-C12alkyl or C2-C12alkenyl; and
R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C6a!kyl, d-C6trihaloalkyl and d-C6trihaloalkoxy.
39. The compound of Claim 38 selected from the group consisting of the
following:

1-(3-MethyI-butyl)-3^5-[4-(2-trffl^
1 -Pentyl-3-{5-[4-(2-trifluoromethyl-benzoyl)-piperazin-1 -yf]-pyridin-2-yf}^urea; and
1 -Butyl-3-{5-[4-(2-trifluoromethyl-benzoyl}-pipera2in-1 -yl}-pyridin-2-yf}~urea.
40. The compound of Claim 37 wherein:
R2 is C7-C12aralkyl optionally substituted by one or more subsfcfeients selected from the group consisting of halo, d-C3alkyi and C-Cgtrihaioa&yt: anc
R3 is phenyl optionally substituted by one or more substituents «jecte.£ from the group consisting of halo, Ci-Ceallcyi, d-Cetrihaioalcyi and C*-C^riTaicaic3r>
41. The compound of Claim 40 selected from the group constsfcng 3f ihe
following:
1-[3-(4-Fluoro-phenyl)-propyI}-3^5-[4^2-tr^
2-yI}-urea;
1-Phenethyl-3-{5-[4-(2-trifluoromethyl-benzoyI^ and
1-Benzyl-3^5-[4-(2-trifluoromethyl-benzoyl^
42. A method of treating a disease or condition mediated by stearoyl-CoA desaturase (SCD) in a mammal, wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of Claim 35.
43. A pharmaceutical composition comprising a pharmaceutical^ acceptable excipient and a therapeutically effective amount of a compound of CSaim 35.
44. A compound of formula (V):

wherein:
x and y are each independently 1, 2 or 3;
Wa is -0-, -N(R1)- or -S(0)r (where t is 0, 1 or 2);

Wa is -O-;
Va is -C(0)-;
R1 is hydrogen or d-C5alkyI;
R2 is selected from the group consisting of C-C12a!kyl. d-C-jafttenyl-C2-C12hydroxyalkyI, C2-Ci2hydroxyaIkenyI, C3-C12alkoxyalkylt Cr-C-zcyctoalky*. C4-Ci2cycloalkylaIkyl, aryl, C7-C19aralkyl, C3-C12 heterocyctyl, d-C-2heterocy^ytafiry' d-Ci2heteroaryl and C3-C12heteroarylalkyl;
R3 is selected from the group consrsting of d-C-jaBcyl Cr-C^-afcer** d-C^hydroxyalkyl, C2-C12hydroxyalkenyl, CVC-^lkoxyalkyl. C3-C-2cyck3alr?». C4-C12cycloalkylalkyI, aryl, d-dgaralkyl, C3-d2heterocyctyl. CrC^heterocycJytafcy d-C12heteroaryl and C3-Ci2heteroaryialkyi;
R4, R5 and R6 are each hydrogen; and
R7, R7a, R8, R8a, R9, R93, R10, and R10a are each hydrogen.
46. The compound of Claim 45 wherein:
R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-dalkyl, Ci-C6trihatoalkyt. d-dtrihaloalkoxy, d-C6alkylsulfonyl, -N(R12)2) -OC(0)R12, -C(0)OR12, -S(0)2N(R12)2, cycloalkyl, heterocyclyl, heteroaryl and heteroarylcycloalkyl; and
each R12 is independently selected from hydrogen, d-C6aIkyI, C3-C6cycloalkyl, aryl or aralkyl.
47. The compound of Claim 44 wherein:
x and y are each 1;
Wais-N(R1K
Va is -C(O)-;
R1 is hydrogen or d-dalkyl;
R2 is selected from the group consisting of d-C12aIkyl, d-Ct2aikenyL C2-Ci2hydroxyalkyl, C2-C12hydroxyalkenyl, C3-C12aIkoxyalkyl, C3-d2cycloalky!. C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12 heterocyclyl, d-Ci2heterocydyta§cyi. CrC^heteroaryl and C3-C12heteroarylalkyl;
R3 is selected from the group consisting of d-d^Ikyl, d-Ci^kenyi, C2-Ci2hydroxyalkyl, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl, drdzcycloalkyl, C4-C12cycloalkylaIkyl, aryl, C7-d9aralkyl, C3-Ci2heterocyclyl, d-C^heterocydylalkyl, d-C12heteroaryl and C3-C12heteroarylalkyl;
R4, R5 and R6 are each hydrogen; and

A pharmaceutical composition comprising a pharmaceutical^ acceptable excipient and a therapeutically effective amount of a compound of C*aim 44.
53. A compound of formula (Via):

x and y are each independently 1, 2 or 3;
R1 is selected from the group consisting of hydrogen, C1-C12alkyt! C2-C12hydroxyalkyl, C4-C12cycloalkyIaIkyl and C7-C19aralkyl;
R2 is selected from the group consisting of Cy-C^alky!, C3-C12alkenylf C7-Ci2hydroxyalkyl, C2-C12alkoxyaIkyl, C3-Ci2hydroxyaIkenyl, (VC^cycIoalkyl, C4-Ci2cycloalkylalkyl, Ci3-Ci9aralkyl, C3-Ci2heterocycIyIalkyI, and C3-C12heteroarylaJkyf;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyctyi, ary! and heteroaryl, where some or all of the rings may be fused to each other
R3 is selected from the group consisting of C3-C12alkyl, C3-C12afcenyt. C3-Ci2hydroxyalkyl, C3-C12hydroxyalkenyl, C3-C12alkoxy, C3-C12alkoxyalkyf, C3-Ci2cycloalkyl, C4-C12cycloaIkylaIkyI, aryl, C7-C19aralkyl, C3-C12heterocyctyL C3-Ci2heterocyclylalkyl, C5-C12 heteroaryl and C3-C12heteroarylaIkyl;
or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyi, aryl and heteroaryl and where some or all of the rings may be fused to each other
R4, R5 and R6 are each independently selected from hydrogen, fkxxo. chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or-N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or d-C3alkyl;
or R7 and R7a together, or R8and R8a together, or R9and R93 together, or R10 and R10a together are an oxo group, provided that when Va is -C(O)-, R7and R7a

57. A compound of formula (Vlb):

wherein:
x and y are each independently 1, 2 or 3;
each R1 is independently selected from the group consisting of hydrogen, d-C^alkyl, C2-C12hydroxyaIkyl, C4-Ci2cyctoafkytalky1 and C-C-r^arafcy*
R2 is selected from the group consisting of C1-C12a8cy!, Cr-Ci2akeny*. C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, d-Ci^lkoxyalkyl, d-d2cyctoalkyt, C4-Ci2cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12 heterocyclyl, d-d2heterocyc*ytafcyl, C^C^heteroaryl and C3-C12heteroarylaIkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other;
R3 is naphthyl or phenyl, each optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, d-C6alkyl, d-Cetrihaloalkyl, d-C6trihaIoalkoxy, d-daikylsulfonyi, -N(R12)2) -OC(0)R12, -C(0)OR12, -S(0)2N(R12)2, cycloalkyl, heterocyclyl, heteroaryl and heteroaryicycloalkyl, provided that R3 is not phenyl substituted with optionally substituted thienyl, and provided that when R3 is naphthyl, R2 can not be d-CeafcyL C2-C6hydroxyalkyl or phenyl substituted by amino;
R4, R5 and R6 are each independently selected from hydrogen, fiuoro. chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or-N(R13)2;
R7, R7a, R8, R8a, R9, R93, R10, and R10a are each independently selected
from hydrogen ord-dalkyl;
or R7 and R7a together, or R8and R8a together, or R9and R93 together, or R10 and R10a together are an oxo group, provided that when Va is -C(O)-, R7and R7s together or R8 and R8a together do not form an oxo group, while the remaining R'. R a. R8, RBa, R9, R9a, R10, and R10a are each independently selected from hydrogen or d-C3alkyl;
or one of R10, R10a, R7, and R7a together with one of R8, R8a, R9 and R93

5-[4-(6-TrifluoromethyLcyclohexa-1^
carboxylic acid (2-cyclohexyl~ethyI)-amide; and 5-[4-(2-TrifIuoromethyl-benzoyl)-piperazirv1-yl]-pyridine-2^artx)xyf»c ackj
cyclohexylmethyl-amide.
65. The compound of Claim 58 wherein:
R2 is C3-Ci2heterocydylaIkyt optionally substituted by one or more substituents selected from the group consisting of hato, cyano, nitro. hydroxy d-Cealkyl, CrC6trihaloalkylt Ct-Cetrihaloalkoxy, C-C5aIkytsu!fonyi. -*4(R*2>2. -OC(0)R12, -C(0)OR12 and -S(0)2N(R12)2;
R3 is phenyl optionally substituted by one or more substituents se^caec from the group consisting of halo, d-C6alkyl, Ci-Cstrihaloalkyl and C^-C^tri^oattcDxy and
each R12 is independently selected from hydrogen, C?-C$a!kyt. C3-C6cycloalkyl, aryl or aralkyl.
66. The compound of Claim 65 wherein R2 is 2-piperazinylethyl optiona&y substituted by-C(0)OR12.
67. The compound of Claim 66, namely, 4-[2-({5-[4-(2-Trifluoromethyl-benzoyl)-piperazin-1-yl]-pyridine-2^arbonyl}-amino)^thyl]-piperazine-1-c3rtx3xylica^ tert-butyl ester.
68. The compound of Claim 58 wherein:
R2 is CrC12araIkyl optionally substituted by one or more substituents selected from the group consisting of halo, d-C^Iky! and Ci-C6trihaloa!kyl; and
R3 is naphthyl optionally substituted by one or more substituents selected from the group consisting of halo, Ci-C6alkyl, C^Cetrihaloalkyl and d-Cetrihaloalkoxy.
69. The compound of Claim 68 selected from the group consisting of the
following:
5-[4-(Naphthalene-1-carbonyl)-piperazin-1-yl]-pyridine-2-carboxylicackj (3-phenyf-
propyl)-amide; and 5-[4-(Naphthalene-1-carbonyl)piperazin-1-yl]pyridine-2-carboxylicacid phenethylamide.

70. A method of treating a disease or condition mediated by stearoyt-CoA
desaturase (SCD) in a mammal, wherein the method comprises administering to a
mammal in need thereof a therapeutically effective amount of a compound of Ctarn 57
71. A pharmaceutical composition comprising a pharmaceutical^
acceptable excipient and a therapeutically effective amount of a compound Off
Claim 57.

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Patent Number

234746

Indian Patent Application Number

356/CHENP/2006

PG Journal Number

29/2009

Publication Date

17-Jul-2009

Grant Date

15-Jun-2009

Date of Filing

27-Jan-2006

Name of Patentee

XENON PHARMACEUTICALS INC

Applicant Address

3650 Gilmore Way, Burnaby, British Columbia V5G 4W8

Inventors:

#	Inventor's Name	Inventor's Address
1	ABREO, Melwyn	3373 Armagosa Way, Jamul, CA 91932
2	KONDRATENKO, Mikhail, A.,	12820 Via Nieve #73, San Diego, CA 92130
3	LI, Wenbao	11674 Castile Way, San Diego, CA 92128
4	KODUMURU, Vishumurthy	211-6577 Royal Oak Avenue, Burnaby, British Columbia V5H 3P3
5	WINTHER, Michael, D.	1935 West 14th Avenue, Vancouver, British Columbia V6J 2K1
6	GSCHWEND, Heinz, W.	161 Meadowcroft Way, Santa Rosa, CA 9540
7	CHAKKA, Nagasree	211-6577 Royal Oak Avenue, Burnaby, British Columbia V5H 3P3
8	SVIRIDOV, Serguei	1904-5885 Olive Avenue, Burnaby, British Columbia V5H 4N8
9	HARVEY, Daniel, F.	6254 Lakewood Street, San Diego, CA 92122
10	KAMBOJ, Rajender	5809 Sperling Avenue, Burnaby, British Columbia V5E 2T6
11	LIU, Shifeng	15-2615 Fortress Drive, Port Coquitlam, British Columbia V3C 6E8
12	SUN, Shaoyi	407-1029 East Broadway, Vancouver, British Columbia V5T 1Y8

PCT International Classification Number

A61K31/00

PCT International Application Number

PCT/US2004/024542

PCT International Filing date

2004-07-29

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	60/491,140	2003-07-29	U.S.A.
2	60/491,080	2003-07-30	U.S.A.
3	60/491,116	2003-07-30	U.S.A.
4	60/491,141	2003-07-30	U.S.A.
5	60/491,322	2003-07-30	U.S.A.