HK1105890A - Nicotinamide derivatives and their use as therapeutic agents - Google Patents

Description

Nicotinamide derivatives and their use as therapeutic agents

Technical Field

The present invention relates generally to inhibitors of stearoyl-coa desaturase, such as nicotinamide derivatives, and also to the use of such compounds in the treatment and/or prevention of a variety of human diseases, including those mediated by stearoyl-coa desaturase (SCD), preferably SCD1, particularly diseases associated with elevated lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome, and the like.

Background

Acyl desaturases catalyze the formation of double bonds in de novo synthesized fatty acids from dietary sources or in the liver. Mammals synthesize at least three different chain length specific fatty acid desaturases that catalyze the introduction of double bonds at the delta-9, delta-6, and delta-5 positions. stearoyl-CoA desaturase enzymes (SCDs) introduce a double bond at the C9-C10 positions of saturated fatty acids. Preferred substrates are palmitoyl-CoA (16: 0) and stearoyl-CoA (18: 0) converted to palmitoyl-CoA (16: 1) and oleoyl-CoA (18: 1), respectively. The resulting monounsaturated fatty acids are substrates for binding to phospholipids, triglycerides and cholesterol esters.

A large number of mammalian SCD genes have been cloned. For example, two genes (SCD1, SCD2) have been cloned from rats and four SCD genes (SCD1, 2, 3, and 4) have been isolated from mice. Although the basic biochemical role of SCD in rats and mice has been known since the 70's of the 19 th century (Jeffcoat, R.et al, Elsevier Science (1984), Vol.4, pp.85-112; de Antueno, RJ, Lipids (1993), Vol.28, No.4, pp.285-290), its basic biochemical role in the course of human disease has not been directly implied until recently.

A single SCD gene, SCD1, has been characterized in humans. SCD1 is described in published PCT patent application WO 01/62954 to Brownlie et al, the disclosure of which is incorporated herein by reference in its entirety. A second subtype of human SCD has recently been identified and, because of its little sequence homology with rat or mouse subtypes, is named human SCD5 or hSCD5 (published PCT patent application WO 02/26944, the entire contents of which are incorporated herein by reference).

To date, non-small molecule drug-like compounds that specifically inhibit or modulate SCD activity are known. Historically, SCD activity has been studied using certain long chain hydrocarbons. Known examples include thio fatty acids, cyclopropene fatty acids, and certain conjugated linoleic acid isomers. In particular, cis-12, trans-10-conjugated linoleic acid is believed to inhibit SCD enzyme activity and reduce the abundance of SCD1 mRNA, whereas cis-9, trans-11-conjugated linoleic acid is not. Cyclopropene fatty acids such as those found in phoenix tree (stercula) seeds and cotton seeds are also known to inhibit SCD activity. For example, phoenix (8- (2-octylcyclopropyl) octanoic acid) and malvalic (7- (2-octylcyclopropyl) heptanoic acid) are C18 and C16 derivatives, respectively, having cyclopropenyl rings at C9-C10 positions. These substances are believed to inhibit the enzymatic activity of SCD by direct interaction with the enzyme, thus inhibiting delta-9 desaturation. Other substances that may inhibit SCD activity include thio fatty acids such as 9-thio stearic acid (also known as 8-nonyl thio octanoic acid) and other fatty acids having a sulfinyl (sulfoxy) moiety.

These known modulators of delta-9 desaturase activity cannot be used to treat diseases and disorders associated with SCD 1. Known SCD inhibitor compounds are not selective for SCD or delta-9 desaturases, as they also inhibit other desaturases and enzymes. Thio fatty acids, conjugated linoleic acid and cyclopropene fatty acids (malvalic and sterculic acids) can neither be used at reasonable physiological doses nor are they specific inhibitors of the biological activity of SCD1, however they show cross-inhibitory effects on other desaturases, especially on delta-5 and delta-6 desaturases.

The lack of small molecule inhibitors of SCD enzyme activity is a major scientific and medical frustration, as compelling evidence now suggests that SCD activity is directly involved in the common human disease process: see, e.g., Attie, A.D.et al, "Relationship between stearoyl-CoAdesaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia," Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia, "Lipid Res. (2002) Vol.43, No.11, pp.1899-907; cohen, P.et al, "" Role for stearoyl-CoAdesaturase-1 in leptin-mediated weight Loss "(" Role of stearoyl-CoA desaturase-1 in leptin-mediated weight Loss "), Science (2002), Vol.297, No.5579, pp.240-3, Ntambi, J.M.et al," "Loss of stearoyl-CoA desaturase-1function protection mice against obesity" (Loss of stearoyl-CoA desaturase-1 function) Proc.Natl.Acad.Sci.USA. (2002), Vol.99, No.7, pp.11482-6.

The present invention solves the above problems by providing a new class of compounds useful for modulating SCD activity and modulating lipid levels, particularly plasma lipid levels, which compounds are useful in the treatment of SCD-mediated diseases such as diseases associated with dyslipidemia and disorders of lipid metabolism, particularly in the treatment of diseases associated with elevated lipid levels, cardiovascular diseases, diabetes, obesity, metabolic syndrome and the like.

Relevant documents

U.S. Pat. No. 6,677,452 discloses novel pyridine carboxamide or pyridine sulfonamide derivative compounds.

Summary of The Invention

The present invention provides methods of using nicotinamide derivatives to modulate the activity of stearoyl-coa desaturase. Pharmaceutical compositions containing such derivatives are also included.

Accordingly, it is an object of the present invention to provide a method of treating an SCD-mediated disease or condition in a mammal, wherein said method comprises administering to said mammal in need thereof a therapeutically effective amount of a compound of formula (I):

wherein:

m is 1, 2 or 3;

n is 1, 2, 3 or 4;

p is 2, 3 or 4;

v is-C (O) -, -S (O) -or-S (O)₂-；

R¹Is hydrogen, alkyl, alkenyl, aryl, heteroaryl, aralkyl, aralkenyl or cycloalkyl;

R²Selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

R³selected from hydrogen, -R⁹-OR⁸、-R⁹-N(R⁸)₂Alkyl, alkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenylOptionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl and optionally substituted heteroaralkenyl;

each R⁴Independently hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl, cyano, nitro, -R⁹-OR⁸、-R⁹-N(R⁸)₂or-S (O)_tR¹⁰(wherein t is 0, 1 or 2);

each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

Or, an R⁵And one R⁶May together form a linear or branched alkylene bridge;

each R⁷Independently a straight or branched alkylene chain or alkenylene chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

each R⁹Independently a direct bond or a straight or branched alkylene or alkenylene chain; and

R¹⁰is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

the compounds may be a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a tautomer;

or a pharmaceutically acceptable salt thereof, a prodrug thereof, a solvate thereof, or a polymorph thereof.

The invention also relates to a method of treating, or preventing, a disease or condition mediated by stearoyl-coa desaturase (SCD), in a subject, wherein the method comprises administering to a subject having, or at risk of having, the disease or condition, a therapeutically effective amount of a compound that, when administered to the subject, inhibits SCD activity in the subject.

The invention also relates to methods of treating a class of diseases involving lipid metabolism using compounds identified by the methods disclosed herein. Thus, disclosed herein is a class of compounds having such activity, based on screening assays, identifying therapeutic agents from a library of test compounds that modulate the biological activity of SCD and that can be used to treat human disorders or conditions associated with serum levels of lipids such as triglycerides, VLDL, HDL, LDL, and/or lipids such as total cholesterol.

It is another object of the present invention to provide compounds or pharmaceutical compositions for the treatment, prevention and/or diagnosis of diseases or disease states associated with SCD biological activity, such as diseases comprising cardiovascular disorders and/or metabolic syndrome (including dyslipidemia, insulin resistance and obesity).

It is another object of the present invention to provide a method for preventing or treating a disease or condition associated with elevated lipid levels, such as plasma lipid levels, in particular elevated triglyceride or cholesterol levels, in a patient having elevated lipid levels, said method comprising administering to said patient a therapeutically or prophylactically effective amount of a composition as disclosed herein. The invention also relates to novel compounds having the therapeutic ability to reduce lipid levels, particularly triglyceride and cholesterol levels, in animals.

The invention also relates to a pharmaceutical composition containing the compound of the general formula (I) and a pharmaceutically acceptable excipient. In one embodiment, the invention relates to a pharmaceutical composition comprising an amount of a compound of the invention in a pharmaceutically acceptable carrier effective, when administered to an animal, preferably a mammal, most preferably a human patient, to modulate triglyceride levels or treat diseases and disorders of lipid metabolism associated with dyslipidemia. In an embodiment of such a composition, the patient has an elevated lipid level, such as elevated plasma triglycerides or cholesterol, prior to administration of the compound and prior to the presence of an amount of the compound effective to reduce the lipid level.

The invention also relates to compounds of general formula (I):

wherein:

m is 1, 2 or 3;

n is 1, 2, 3 or 4;

p is 2, 3 or 4;

v is-C (O) -, -S (O) -or-S (O)₂-；

R¹Is hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl or cycloalkyl;

R²selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

R³Selected from cycloalkyl substituted with one or more substituents independently selected from alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclylAlkyl, heteroaryl, heteroaralkyl, -R⁹-OR⁸、-R⁹-N(R⁸)₂、-R⁹-C(O)R⁸、-R⁹-C(O)OR⁸、-R⁹-C(O)N(R⁸)₂、-R⁹-N(R⁸)C(O)OR₁₀、-R⁹-N(R⁸)C(O)R₁₀、-R⁹-N(R⁸)(S(O)_tR¹⁰) (wherein t is 1 or 2), -R⁹-S(O)_tOR¹⁰(wherein t is 1 or 2), -R⁹-S(O)_tR¹⁰(wherein t is 0, 1 or 2) and-R⁹-S(O)_tN(R⁸)₂(wherein t is 1 or 2);

each R⁴Independently hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl, cyano, nitro, -R⁹-OR⁸、-R⁹-N(R⁸)₂or-S (O)_tR¹⁰(wherein t is 0, 1 or 2);

each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

or, an R⁵And one R⁶May together form a linear or branched alkylene bridge;

each R⁷Independently a straight or branched alkylene chain or alkenylene chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

each R⁹Independently a direct bond or a straight or branched alkylene or alkenylene chain; and

R¹⁰is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

The compounds may be a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a tautomer;

or a pharmaceutically acceptable salt thereof, a prodrug thereof, a solvate thereof, or a polymorph thereof.

Brief description of the drawings

Figure 1 shows the dose response curves for two compounds of the invention. Compounds on the left side of the figure (IC)₅₀100nM) shows the compound (IC) to the right₅₀2.4. mu.M) higher inhibitory ability.

Detailed description of the invention

Definition of

Unless expressly indicated to the contrary, the following terms used in the specification and appended claims have the following meanings:

"alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, free of unsaturation, having from 1 to 12 carbon atoms, preferably from 1 to 8 carbon atoms, and attached by a single bond to the rest of the molecule, such as methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, 1-dimethylethyl (tert-butyl), and the like.

"alkenyl" means a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing at least one double bond, having from 1 to 12 carbon atoms, preferably from 1 to 8 carbon atoms, and attached to the rest of the molecule by a single bond, such as ethenyl, 1-propenyl, 1-but-1-enyl, 1-pentenyl, 1, 4-pentadienyl, and the like.

"aryl" refers to an aromatic monocyclic or polycyclic hydrocarbon ring system, said aryl being exclusivelyConsisting of carbon atoms and hydrogen atoms, having 6 to 19 carbon atoms, wherein 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 otherwise specifically stated in the specification, the term "aryl" or the prefix "aryl" (for example in "aralkyl") is intended to include aryl groups optionally substituted with one or more substituents independently selected from alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, -R⁹-OR⁸、-R⁹-N(R⁸)₂、-R⁹-C(O)R⁸、-R⁹-C(O)OR⁸、-R⁹-C(O)N(R⁸)₂、-R⁹-N(R⁸)C(O)OR¹⁰、-R⁹-N(R⁸)C(O)R¹⁰、-R⁹-N(R⁸)(S(O)_tR¹⁰) (wherein t is 1 or 2), -R⁹-S(O)_tOR¹⁰(wherein t is 1 or 2), -R⁹-S(O)_tR¹⁰(wherein t is 0, 1 or 2) and-R⁹-S(O)_tN(R⁸)₂(wherein t is 1 or 2) wherein each R⁸、R⁹And R¹⁰As defined in the summary of the invention above.

"aralkyl" refers to the formula-R_aR_bWherein R is_aIs an alkyl group as defined above and R_bIs one or more aryl groups as defined above, aralkyl being for example benzyl, benzhydryl and the like. The aryl group may be optionally substituted as described above.

"aralkenyl" refers to the formula-R_cR_bWherein R is_cIs an alkenyl group as defined above and R_bIs one or more aryl groups as defined above, which may be optionally substituted as described above.

"alkylene" and "alkylene chain" refer to a straight or branched divalent hydrocarbon chain connecting the remainder of the molecule to a group, consisting only of carbon and hydrogen atoms, containing no unsaturation, and having from 1 to 12 carbon atoms, preferably from 1 to 8 carbon atoms, such as methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain may be linked to the rest of the molecule and the group by any two carbons in the chain.

"alkylene" and "alkylene bridge" refer to a straight or branched chain divalent hydrocarbon bridge that connects two different carbons of the same ring structure, consists only of carbon atoms and hydrogen atoms, contains no unsaturation, and has 1 to 12 carbon atoms, preferably 1 to 8 carbon atoms, for example, methylene, ethylene, propylene, n-butylene, and the like. The alkylene bridge may connect any two carbons in the ring structure.

"alkenylene" and "alkenylene chain" refer to a straight or branched divalent hydrocarbon chain connecting the rest of the molecule to a group, consisting only of carbon and hydrogen atoms, containing at least one double bond, and having from 2 to 7 carbon atoms, such as for example ethenylene, propenylene, n-butenyl, and the like. The alkenylene chain may be connected to the rest of the molecule by single bonds and to groups by double or single bonds. The point of attachment of the alkenylene chain to the rest of the molecule and its point of attachment to a group may be any two carbons in the chain.

"cycloalkyl" refers to a stable non-aromatic monocyclic or bicyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms and having from 3 to 15 carbon atoms, preferably from 3 to 10 carbon atoms, which is saturated or unsaturated and is linked to the remainder of the molecule by a single bond, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, decahydronaphthyl and the like. Unless otherwise specifically stated in the specification, the term "cycloalkyl" is intended to include cycloalkyl groups optionally substituted with one or more substituents independently selected from alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkylRadical, heteroaryl, heteroaralkyl, -R⁹-OR⁸、-R⁹-N(R⁸)₂、-R⁹-C(O)R⁸、-R⁹-C(O)OR⁸、-R⁹-C(O)N(R⁸)₂、-R⁹-N(R⁸)C(O)OR¹⁰、-R⁹-N(R⁸)C(O)R¹⁰、-R⁹-N(R⁸)(S(O)_tR¹⁰) (wherein t is 1 or 2), -R⁹-S(O)_tOR¹⁰(wherein t is 1 or 2), -R⁹-S(O)_tR¹⁰(wherein t is 0, 1 or 2) and-R⁹-S(O)_tN(R⁸)₂(wherein t is 1 or 2) wherein each R⁸、R⁹And R¹⁰As defined in the summary of the invention above.

"Cyclohydrocarbylalkyl" refers to the formula-R_aR_dWherein R is_aIs an alkyl group as defined above and R_dIs a cyclic hydrocarbyl group as defined above. The alkyl groups and cycloalkyl groups may be optionally substituted as described above.

"halo" refers to bromo, chloro, fluoro, or iodo.

"haloalkyl" refers to an alkyl group as defined above substituted with one or more halo groups as defined above, such as trifluoromethyl, difluoromethyl, trichloromethyl, 2, 2, 2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, 3-bromo-2-fluoropropyl, 1-bromomethyl-2-bromoethyl, and the like.

"haloalkenyl" refers to an alkenyl group as defined above substituted with one or more halo groups as defined above, such as 2-bromovinyl, 3-bromoprop-1-enyl, and the like.

"heterocyclyl" refers to a stable 3-to 18-membered non-aromatic cyclic group consisting of carbon atoms and 1 to 5 heteroatoms selected from nitrogen, oxygen, sulfur. For the purposes of the present invention, the heterocyclyl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic system, which may include fused or bridged ringsIs a step of; and the nitrogen, carbon or sulfur atom in the heterocyclyl group may be optionally oxidized; the nitrogen atoms may optionally be quaternized; and the heterocyclyl group may be partially or fully saturated. Examples of such heterocyclyl groups include, but are not limited to, dioxolanyl, decahydroisoquinolinyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidinonyl, pyrrolidinyl, pyrazolidinyl, thiazolidinyl, tetrahydrofuranyl, trithianyl, tetrahydropyranyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, and 1, 1-dioxo-thiomorpholinyl. Unless otherwise specifically stated in the specification, the term "heterocyclyl" is intended to include a heterocyclyl group as defined above optionally substituted with one or more substituents independently selected from alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, -R ⁹-OR⁸、-R⁹-N(R⁸)₂、-R⁹-C(O)R⁸、-R⁹-C(O)OR⁸、-R⁹-C(O)N(R⁸)₂、-R⁹-N(R⁸)C(O)OR¹⁰、-R⁹-N(R⁸)C(O)R¹⁰、-R⁹-N(R⁸)(S(O)_tR¹⁰) (wherein t is 1 or 2), -R⁹-S(O)_tOR¹⁰(wherein t is 1 or 2), -R⁹-S(O)_tR¹⁰(wherein t is 0, 1 or 2) and-R⁹-S(O)_tN(R⁸)₂(wherein t is 1 or 2) wherein each R⁸、R⁹And R¹⁰As defined in the summary of the invention above.

"Heterocyclylalkyl" refers to the formula-R_aR_eWherein R is_aIs an alkyl group as defined above and R_eIs a heterocyclic group as defined above and if said heterocyclic group is a nitrogen-containing heterocyclic groupThe heterocyclic group may then be attached to the alkyl group at the nitrogen atom. The heterocyclyl group may be optionally substituted as described above.

"heteroaryl" refers to a 3-to 18-membered aromatic ring group consisting of carbon atoms and 1 to 5 heteroatoms selected from nitrogen, oxygen, sulfur. For the purposes of the present invention, the heterocyclyl group may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused or bridged ring systems; and the nitrogen, carbon or sulfur atom in the heteroaryl group may be optionally oxidized; the nitrogen atoms may optionally be quaternized. Examples include, but are not limited to, azanyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzothiadiazolyl, benzonaphthofuranyl (benzonaphthofuranyl), benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothiophenyl (benzothiophenyl), benzotriazolyl, benzo [4, 6 ] benzo ]Imidazo [1, 2-a ]]Pyridyl, carbazolyl, cinnolinyl, dibenzofuranyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazatrolyl, oxazolyl, oxiranyl, phenazinyl, phenothiazinyl, phenoxazinyl, 2, 3-naphthyridinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolyl, quinuclidinyl, isoquinolyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl. Unless otherwise specifically stated in the specification, the term "heteroaryl" is intended to include heteroaryl groups as defined above optionally substituted by one or more substituents selected from alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, -R⁹-OR⁸、-R⁹-N(R⁸)₂、-R⁹-C(O)R⁸、-R⁹-C(O)OR⁸、-R⁹-C(O)N(R⁸)₂、-R⁹-N(R⁸)C(O)OR¹⁰、-R⁹-N(R⁸)C(O)R¹⁰、-R⁹-N(R⁸)(S(O)_tR¹⁰) (wherein t is 1 or 2), -R⁹-S(O)_tOR¹⁰(wherein t is 1 or 2), -R⁹-S(O)_tR¹⁰(wherein t is 0, 1 or 2) and-R ⁹-S(O)_tN(R⁸)₂(wherein t is 1 or 2) wherein each R⁸、R⁹And R¹⁰As defined in the summary of the invention above.

"Heteroaralkyl" means a group of the formula-R_aR_fWherein R is_aIs an alkyl group as defined above and R_fIs a heteroaryl group as defined above. The heteroaryl group may be optionally substituted as described above.

"Heteroaralkenyl" means a group of formula-R_bR_fWherein R is_bIs an alkenyl group as defined above and R_fIs a heteroaryl group as defined above. The heteroaryl group may be optionally substituted as described above.

"prodrug" is intended to mean a compound that can be converted to the biologically active compounds of the invention under physiological conditions or by solvolysis. Thus, the term "prodrug" relates to a metabolic precursor of a compound of the invention, which is pharmaceutically acceptable. When administered to a subject in need thereof, the prodrug may be inactive, but may be converted in vivo to the active compound of the invention. Prodrugs are generally rapidly converted in vivo, for example, by hydrolysis in blood, to yield the parent compound of the invention. Prodrug compounds often provide advantageous solubility, histocompatibility, or delayed release in the organs of mammals (see Bundgard, h., Design of produgs (1985), pp.7-9, 21-24(Elsevier, Amsterdam)).

Higuchi, T.T., et al, "Pro-drugs as Novel Delivery Systems," (prodrugs as the Novel Delivery system) A.C.S.Sympossium Series, Vol.14 and BioversibleCarriers in Drug Design, ed.Edward B.Roche, American Pharmaceutical Association and Pergamon Press, 1987 provide a discussion of prodrugs, the entire contents of which are incorporated herein by reference.

The term "prodrug" is also intended to include any covalently bonded carriers that release the active compounds of the present invention in vivo when the prodrug is administered to a mammalian subject. Prodrugs of the compounds of the present invention are prepared by modifying functional groups present in the compounds of the present invention in such a way that: where the modification is cleaved, either in routine manipulation or in vivo, to the parent compound of the invention. Prodrugs include compounds of the present invention wherein a hydroxy, amino, or sulfhydryl group is bonded to any group that, when the prodrug of the compound of the present invention is administered to a mammalian subject, dissociates to form a free hydroxy, free amino, or free sulfhydryl group, respectively. Examples of prodrugs include, but are not limited to, ester or amide derivatives of hydroxy, carbonyl, mercapto or amino functional groups in the compounds of the present invention, and the like.

"stable compounds" and "stable structures" are intended to mean that the compounds are sufficiently stable to be isolated in useful purity from a reaction mixture and formulated into an effective therapeutic agent.

"mammal" includes humans and domestic animals, such as cats, dogs, pigs, cattle, sheep, goats, horses, rabbits, and the like.

"any" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. For example, "optionally substituted aryl" means that the aryl group may or may not be substituted, and that the description includes both substituted aryl groups and unsubstituted aryl groups.

A "pharmaceutically acceptable carrier, diluent or excipient" includes, but is not limited to, any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye/colorant, flavor enhancer, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier that is acceptable for use by the U.S. food and drug administration in humans and livestock.

"pharmaceutically acceptable salts" include acid addition salts and base addition salts.

"pharmaceutically acceptable acid addition salts" refer to those salts that retain biological effectiveness and free base properties, which are not biologically or otherwise unsuitable and are formed using inorganic acids such as, but not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, or organic acids such as, but not limited to, acetic acid, 2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, camphoric acid, camphor-10-sulfonic acid, capric acid, hexanoic acid, octanoic acid, carbonic acid, cinnamic acid, citric acid, cyclohexylsulfamic acid, dodecylsulfuric acid, ethane-1, 2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, mucic acid (galactaric acid), Gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid (mucic acid), naphthalene-1, 5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid, undecylenic acid, and the like.

"pharmaceutically acceptable base addition salts" refers to those salts that retain biological effectiveness and free acid properties, and are not biologically or otherwise unsuitable. These salts are prepared by the inorganic or organic addition of an inorganic or organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Preferred inorganic salts are ammonium, sodium, potassium, calcium and manganese salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary and tertiary amines, salts of substituted amines including naturally occurring substituted amines, salts of cyclic amines and basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, benzylamine, phenylenediamine, ethylenediamine, glucosamine, methylglucamine, theobromine, triethanolamine, tromethamine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, and the like. Particularly preferred organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.

The compounds of the present invention may, and typically are, present in solid form, which includes crystalline solids that can be crystallized from common solvents such as ethanol, N-dimethylformamide, water, or the like. Depending on the crystallization conditions, the crystallization process can provide a variety of polymorphic structures. In general, the more thermodynamically stable polymorph is advantageous for commercial scale preparation of the compounds of the present invention and is the preferred form of the compound. Such polymorphs are also considered to be within the scope of the present invention.

Crystallization often yields solvates of the compounds of the invention. As used herein, the term "solvate" refers to an aggregate comprising one or more molecules of the compound of the present invention with one or more molecules of a 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 in the form of hydrates, including the monohydrate, dihydrate, hemihydrate, sesquihydrate, trihydrate, tetrahydrate, and the like, as well as in the corresponding solvated forms. The compounds of the present invention may be true solvates, while in other cases the compounds of the present invention may also retain only adventitious water or the compounds may be mixtures of water and certain adventitious solvents.

"pharmaceutical composition" refers to a formulation formed from a compound of the present invention and a vehicle generally accepted in the art for delivery of biologically active compounds to a mammal, such as a human. Such a medium therefore includes all pharmaceutically acceptable carriers, diluents or excipients.

A "therapeutically effective amount" refers to an amount 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 the compound of the present invention that constitutes a "therapeutically effective amount" will vary depending on the compound, the disease state and its severity, and the age of the mammal to be treated, but can be routinely determined by one of ordinary skill in the art based on his knowledge and this disclosure.

As used herein, "treating" and "treatment" encompass treating a disease or condition of interest in a mammal, preferably a human, having the disease or condition of interest, including:

(i) preventing a disease or condition from occurring in a mammal, particularly when such mammal is susceptible to said disease condition, but has not yet been diagnosed as having such disease condition;

(ii) Inhibiting, i.e. preventing the occurrence of, said disease or disease state;

(iii) alleviating the disease or condition, even if the disease or condition subsides.

As used herein, the terms "disease" and "disease state" may be used interchangeably or may be different in that a particular disease or disease state may not have a known causative agent (and therefore cannot be resolved etiologically) and is therefore not recognized as a disease but rather an inappropriate disease state or symptom, where a more or less specific set of symptoms has been identified by a clinician.

The compounds of the present invention, or pharmaceutically acceptable salts thereof, may contain one or more asymmetric centers and may thus give rise to enantiomers, diastereomers and other stereoisomeric forms, which may be defined as (R) -or (S) -or as (D) -or (L) -of amino acids, in terms of absolute stereochemistry. The present invention is intended to include all such possible isomers, as well as racemic and optically pure forms thereof. Optically active (+) and (-), (R) -and (S) -or (D) -and (L) -isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques such as HPLC using a chiral column. When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, the compounds are intended to include both E and Z geometric isomers unless specifically indicated otherwise. Likewise, all tautomeric forms are also intended to be included.

"stereoisomers" refers to compounds made up of the same atoms bonded by the same bonds, but having different three-dimensional structures that are not interchangeable. The present invention includes various stereoisomers and mixtures thereof and includes "enantiomers" which refer to two stereoisomers whose molecules are nonsuperimposable mirror images of each other.

"tautomer" refers to the movement of a proton from one atom of a molecule to another atom of the same molecule. The invention includes tautomers of any of the compounds.

The chemical nomenclature and structure diagrams used herein are used and depend on the chemical nomenclature used in chemdraw version 7.0.1 (available from Cambridge corp., Cambridge, MA). For a complex chemical name as used herein, a substituent is named before the group to which it is attached. In the chemical structure diagrams, all bonds are equivalent except for certain carbon atoms that are assumed to bond enough hydrogen atoms to complete the valency. For example, the compound of the formula is named herein as 6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide.

Embodiments of the invention

With respect to the various embodiments of the invention described in the summary of the invention above, one group of embodiments relates to a method of treating an SCD-mediated disease or condition in a mammal, wherein the compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2 or 3; v is-C (O) -or-S (O) ₂-；R¹Is hydrogen or alkyl; r²Selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group; r³Is alkyl, alkenyl or-R⁹-N(R⁸)₂(ii) a Each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸(ii) a Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl; or, an R⁵And one R⁶May together form a linear or branched alkylene bridge; each R⁷Independently a straight or branched alkylene chain or alkenylene chain; each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl; each R⁹Independently a direct bond or a straight or branched alkylene chain; and R ¹⁰Is alkyl, aryl orAn aralkyl group.

With respect to this group of embodiments, a subset of embodiments relate to the method, wherein the compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl; r³Is an alkyl group; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl; each R⁷Is a straight or branched alkylene chain; each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, and aralkyl; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this subgroup of embodiments, one class of embodiments relates to said method, wherein said compound of formula (I) is a compound of formula (I) wherein m is 1; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2) or alkyl; r³Is an alkyl group; r⁴Is hydrogen; r⁵Is hydrogen; each R⁶Is hydrogen; r⁷Is a straight or branched alkylene chain; r ⁸Is hydrogen or alkyl; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this set of embodiments above, another subgroup of embodiments relates to said method, wherein said compound of general formula (I) is a compound of general formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2 or 3; v is-C (O) -or-S (O)₂-；R¹Is hydrogen or alkyl; r²Selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heteroalkenylCyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkenyl; r³Is alkyl or-R⁹-N(R⁸)₂(ii) a Each R⁴Independently hydrogen, alkyl, halo or haloalkyl; and each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl; or, an R⁵And one R⁶May together form a linear or branched alkylene bridge; r⁷Is a direct bond; and each R⁸Independently hydrogen or alkyl.

With respect to this subgroup of embodiments, one class of embodiments relates to said method, wherein said compound of formula (I) is a compound of formula (I) wherein m is 1; n is 1; p is 2 or 3; v is-C (O) -or-S (O) ₂-；R¹Is hydrogen or alkyl; r²Selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl; r³Is alkyl or-R⁹-N(R⁸)₂；R⁴Is hydrogen, alkyl, halo or haloalkyl; and each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl; or, an R⁵And one R⁶May together form a methylene bridge; r⁷Is a direct bond; and each R⁸Independently hydrogen or alkyl.

With respect to the various embodiments of the invention described in the summary of the invention above, another set of embodiments is directed to a method of treating an SCD-mediated disease or condition in a mammal, wherein the compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted arylOptionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl and optionally substituted heteroaralkenyl; r ³Is an optionally substituted cycloalkyl, an optionally substituted cycloalkylalkyl, an optionally substituted cycloalkylalkenyl; each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸(ii) a Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl; each R⁷Independently a straight or branched alkylene chain or alkenylene chain; each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl; r⁹Is a direct bond or is a straight or branched alkylene chain; and R¹⁰Independently an alkyl, aryl or aralkyl group.

With respect to this group of embodiments, a subset of embodiments relate to the method, wherein the compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl; r³Is optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl; each R ⁴Independently hydrogen, alkyl, halo or haloalkyl; each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl; each R⁷Independently a straight or branched alkylene chain; each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; and R¹⁰Independently an alkyl, aryl or aralkyl group.

With respect to this subgroup of embodiments, one class of embodiments relates to said method, wherein said compound of formula (I) is a compound of formula (I) wherein m is 1; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2) or alkyl; r³Is optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl; r⁴Is hydrogen; r⁵Is hydrogen; each R⁶Is hydrogen; r⁷Is a straight or branched alkylene chain; r⁸Is hydrogen or alkyl; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this set of embodiments above, another subgroup of embodiments relates to said method, wherein said compound of general formula (I) is a compound of general formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, and optionally substituted heteroaralkenyl; r ³Is optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; and each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

With respect to this subgroup of embodiments, one class of embodiments relates to said method, wherein said compound of formula (I) is a compound of formula (I) wherein m is 1; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl; r³Is an optionally substituted cycloalkyl groupOr optionally substituted cycloalkylalkyl; r⁴Independently hydrogen, alkyl, halo or haloalkyl; r⁵Independently hydrogen, oxo, alkyl, halo or haloalkyl; and each R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

With respect to the various embodiments of the invention described in the summary of the invention above, another set of embodiments is directed to a method of treating an SCD-mediated disease or condition in a mammal, wherein the compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r ¹Is hydrogen or alkyl; r²Selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group; r³Is an optionally substituted aryl group; each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸(ii) a Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl; each R⁷Independently a straight or branched alkylene chain or alkenylene chain; each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl; r⁹Is a direct bond or is a straight or branched alkylene chain; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this group of embodiments, a subset of embodiments relate to the method, wherein the compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C ( O)-；R¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl; r³Is an optionally substituted aryl group; each R⁴Independently is hydrogen, alkyl, halo, haloalkyl or-R⁹-OR⁸(ii) a Each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl; each R⁷Is a straight or branched alkylene chain; each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; r⁹Is a direct bond or is a straight or branched alkylene chain; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this subgroup of embodiments, one class of embodiments relates to said method, wherein said compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an optionally substituted cycloalkyl group or an optionally substituted cycloalkylalkyl group; r³Is an optionally substituted aryl group; each R⁴Independently is hydrogen, halo, haloalkyl or-R⁹-OR⁸；R⁵Is hydrogen; each R⁶Is hydrogen; r⁷Is a straight or branched alkylene chain; r ⁸Is hydrogen or alkyl; r⁹Is a direct bond or is a straight or branched alkylene chain; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this set of embodiments above, another subgroup of embodiments relates to said method, wherein said compound of general formula (I) is a compound of general formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from optionally substituted aryl, optionally substituted arylOptionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl and optionally substituted heteroaralkenyl; r³Is an optionally substituted aryl group; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; and each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

With respect to this subgroup of embodiments, one class of embodiments relates to said method, wherein said compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl; r ³Is an optionally substituted aryl group; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; r⁵Is hydrogen, oxo, alkyl, halo or haloalkyl; and each R⁶Independently hydrogen, alkyl, halo or haloalkyl.

With respect to the various embodiments of the invention described in the summary of the invention above, another set of embodiments is directed to a method of treating an SCD-mediated disease or condition in a mammal, wherein the compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkene groupA group; r³Is optionally substituted heteroaryl, optionally substituted heteroaralkyl or optionally substituted heteroaralkenyl; each R⁴Independently hydrogen, alkyl, alkenyl, halo, haloalkyl or aryl; each R ⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl; each R⁷Independently a straight or branched alkylene chain or alkenylene chain; each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this group of embodiments, a subset of embodiments relate to the method, wherein the compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl; r³Is optionally substituted heteroaryl, optionally substituted heteroaralkyl or optionally substituted heteroaralkenyl; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl; each R⁷Is a straight or branched alkylene chain; each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; and R ¹⁰Is alkyl, aryl or aralkyl.

With respect to this subgroup of embodiments, one class of embodiments relates to said method, wherein said compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2) or alkyl; r³Is optionally substituted heteroaryl, optionally substituted heteroaralkyl or optionally substituted heteroaralkenyl; each R⁴Independently hydrogen, halo or haloalkyl; r⁵Is hydrogen; each R⁶Is hydrogen; r⁷Is a straight or branched alkylene chain; r⁸Is hydrogen or alkyl; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this set of embodiments above, another subgroup of embodiments relates to said method, wherein said compound of general formula (I) is a compound of general formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, and optionally substituted heteroaralkenyl; r³Is optionally substituted heteroaryl, optionally substituted heteroaralkyl or optionally substituted heteroaralkenyl; each R ⁴Independently hydrogen, alkyl, halo or haloalkyl; and each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

With respect to this subgroup of embodiments, one class of embodiments relates to said method, wherein said compound of formula (I) is a compound of formula (I) wherein m is 1; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl; r³Is optionally substituted heteroaryl, optionally substituted heteroaralkyl or optionally substituted heteroaralkenyl; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; r⁵Is hydrogen, oxo, alkyl, halo or haloalkyl; and each R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

With respect to the various embodiments of the invention described in the summary of the invention above, another set of embodiments is directed to a method of treating an SCD-mediated disease or condition in a mammal, wherein the compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r ¹Is hydrogen or alkyl; r²Selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group; r³Is an optionally substituted aralkyl group or an optionally substituted aralkenyl group; each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸(ii) a Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl; each R⁷Independently a straight or branched alkylene chain or alkenylene chain; each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl; r⁹Is a direct bond or is a straight or branched alkylene chain; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this group of embodiments, a subset of embodiments relate to the method, wherein the compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r ¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl orOptionally substituted cycloalkylalkenyl; r³Is an optionally substituted aralkyl group or an optionally substituted aralkenyl group; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl; each R⁷Is a straight or branched alkylene chain; each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this subgroup of embodiments, one class of embodiments relates to said method, wherein said compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is O, 1 or 2) or alkyl; r³Is an optionally substituted aralkyl group or an optionally substituted aralkenyl group; each R⁴Independently hydrogen, halo or haloalkyl; r⁵Is hydrogen; each R⁶Is hydrogen; r⁷Is a straight or branched alkylene chain; r⁸Is hydrogen or alkyl; and R¹⁰Is alkyl, aryl or aralkyl.

With respect to this set of embodiments above, another subgroup of embodiments relates to said method, wherein said compound of general formula (I) is a compound of general formula (I) wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r ¹Is hydrogen or alkyl; r²Selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, and optionally substituted heteroaralkenyl; r³Is an optionally substituted aralkyl group or an optionally substituted aralkenyl group; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; and each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

With respect to this subgroup of embodiments, one class of embodiments relates to said method, wherein said compound of formula (I) is a compound of formula (I) wherein m is 1 or 2; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl; r³Is an optionally substituted aralkyl group or an optionally substituted aralkenyl group; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; r⁵Is hydrogen, oxo, alkyl, halo or haloalkyl; and each R ⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

With respect to the various embodiments of the invention described in the summary of the invention above, another set of embodiments is directed to a method of treating an SCD-mediated disease or condition in a mammal, wherein the mammal is a human. With respect to this group of embodiments, a subset of embodiments pertain to the methods wherein the disease or condition is one associated with serum levels of triglycerides, VLDL, HDL, LDL, total cholesterol, or reverse transport of cholesterol. Another subset of embodiments relates to the method, wherein the disease or condition is a disease or condition associated with serum triglyceride levels. Another subset of embodiments relates to the method, wherein the disease or condition is a disease or condition associated with serum cholesterol levels. Another subset of embodiments relates to the method, wherein the disease or condition is selected from the group consisting of type II diabetes, impaired glucose tolerance, insulin resistance, hypertension, obesity, hypertriglyceridemia, low HDL, dyslipidemia, microalbuminemia (microalbuminemia), hyperuricemia, hypercoagulable state (hypercoagulability), hyperleptinemia, metabolic syndrome, and any combination thereof. Of these subgroups, several classes of embodiments relate to said method, wherein said disease or condition is type II diabetes, obesity, dyslipidemia, and/or metabolic syndrome.

With respect to the pharmaceutical compositions of the present invention described in the summary of the invention above, one set of embodiments is directed to the pharmaceutical compositions wherein the therapeutically effective amount of the compound of formula (I) is an amount effective, when administered to a mammal, to modulate the lipid level of the mammal. Within this group of embodiments, a subset of embodiments are wherein the lipid is a triglyceride. Another subset of embodiments is wherein the lipid is cholesterol. Another group of embodiments is directed to pharmaceutical compositions wherein the therapeutically effective amount of a compound of formula (I) is an amount effective to modulate HDL-cholesterol levels when administered to a mammal.

With respect to the compounds of formula (I) described in the summary of the invention above, one group of embodiments relates to compounds of formula (I) wherein m is 1, 2 or 3; n is 1, 2, 3 or 4; p is 2, 3 or 4; v is-C (O) -, -S (O) -or-S (O)₂-；R¹Is hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl or cycloalkyl; r²Selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group; r ³Selected from cycloalkyl substituted with one or more substituents independently selected from alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, -R⁹-OR⁸、-R⁹-N(R⁸)₂、-R⁹-C(O)R⁸、-R⁹-C(O)OR⁸、-R⁹-C(O)N(R⁸)₂、-R⁹-N(R⁸)C(O)OR¹⁰、-R⁹-N(R⁸)C(O)R¹⁰、-R⁹-N(R⁸)(S(O)_tR¹⁰) (wherein t is 1 or 2), -R⁹-S(O)_tOR¹⁰(wherein t is 1 or 2), -R⁹-S(O)_tR¹⁰(wherein t is 0, 1 or 2) and-R⁹-S(O)_tN(R⁸)₂(wherein t is 1 or 2); each R⁴Independently hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl, cyano, nitro, -R⁹-OR⁸、-R⁹-N(R⁸)₂or-S (O)_tR¹⁰(wherein t is 0, 1 or 2); each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl; or, an R⁵And one R⁶May together form a linear or branched alkylene bridge; each R⁷Independently a straight or branched alkylene chain or alkenylene chain; each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl; each R⁹Independently a direct bond or a straight or branched alkylene or alkenylene chain; and R¹⁰Is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl.

Within this group of embodiments, a subset of the embodiments pertain to the compounds, where R³Is cyclopropyl substituted with optionally substituted aryl or optionally substituted heteroaryl.

One class of embodiments of this subgroup of embodiments relates to said compounds, wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl groupOptionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl and optionally substituted heteroaralkenyl; each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸(ii) a Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl; each R⁷Independently a straight or branched alkylene chain or alkenylene chain; each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl; r ⁹Is a direct bond or is a straight or branched alkylene chain; and R¹⁰Is alkyl, aryl or aralkyl.

Within this class of embodiments, a subclass of embodiments relates to said compounds, wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, and optionally substituted heteroaralkenyl; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

Within this subclass of embodiments, one set of embodiments pertains to said compounds, wherein m is 1; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Is optionally substituted aralkyl, optionally substituted heteroaralkyl or optionally substituted heterocyclylaryl; r³Is cyclopropyl substituted by phenyl; r⁴Is hydrogen, alkyl, halo or haloalkyl; r⁵Is hydrogen, oxo, alkyl, halo or haloalkyl; and each R⁶Is hydrogen.

Within the above class of embodiments, another subclass of embodiments relates to the compounds, wherein m is 1 or 2; n is 1 or 2; p is 2; v is-C (O) -; r ¹Is hydrogen or alkyl; r²Is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl; each R⁴Independently hydrogen, alkyl, halo or haloalkyl; each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl; each R⁷Is a straight or branched alkylene chain; each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, and aralkyl; and R¹⁰Is alkyl, aryl or aralkyl.

Within this subclass of embodiments, one set of embodiments pertains to said compounds, wherein m is 1; n is 1; p is 2; v is-C (O) -; r¹Is hydrogen or alkyl; r²Selected from alkyl, -R⁷-OR⁸、-R⁷-N(R⁸)₂or-R⁷-S(O)_tR¹⁰(wherein t is 0); r³Is cyclopropyl substituted by phenyl; r⁴Is hydrogen; r⁵Is hydrogen; each R⁶Is hydrogen; r⁷Is a straight or branched alkylene chain; r⁸Is hydrogen or alkyl; and R¹⁰Is alkyl, aryl or aralkyl.

Of the above compounds, the most preferred compounds are selected from the following:

6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

N- (1-methyl-3-phenyl-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

N- (3-isopropoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide; and

n- (2-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide. In addition to the compounds described above, other specific embodiments of the present invention are set forth in example 10 below.

In another embodiment, the methods of the invention relate to the treatment and/or prevention of diseases mediated by stearoyl-coa desaturase (SCD), especially human SCD (hscd), preferably diseases associated with dyslipidemia and disorders of lipid metabolism, and especially diseases associated with elevated plasma lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome, and the like, by administering an effective amount of an agent of the invention.

Effect and testing of Compounds of the invention

The present invention relates to compounds, pharmaceutical compositions and methods of using the same for the treatment and/or prevention of diseases mediated by stearoyl-coa desaturase (SCD), particularly human SCD (hscd), preferably diseases associated with dyslipidemia and disorders of lipid metabolism, and particularly diseases associated with elevated plasma lipid levels, particularly cardiovascular diseases, diabetes, obesity, metabolic syndrome and the like, by administering to a patient in need thereof an effective amount of a modulator, particularly an inhibitor, of SCD.

In general, the present invention provides a method of treating a patient suffering from, or preventing the development of, a disease and/or disorder associated with dyslipidemia, wherein the lipid level of an animal, especially a human, is outside the normal range (i.e. abnormal lipid levels, such as elevated plasma lipid levels), especially higher than normal, preferably wherein the lipid is a fatty acid, such as a free or conjugated fatty acid, a triglyceride, a phospholipid, or cholesterol, for example wherein the LDL-cholesterol level is elevated or the HDL-cholesterol is reduced, or any combination thereof, or wherein the disease state or condition associated with lipid is an SCD-mediated disease or condition, in a patient suffering from, or preventing the development of, a disease and/or disorder associated with dyslipidemia, in a patient, which method comprises administering to the animal a therapeutically effective amount of a compound of formula (I) or a pharmaceutical composition comprising a compound of formula (I), such as a mammalian, especially human, patient, wherein the compound modulates the activity of SCD, preferably human SCD 1.

All of these compounds modulate, preferably inhibit, the activity of human SCD enzyme, particularly the activity of human SCD 1.

The general value of the compounds of the present invention in modulating, especially inhibiting, SCD activity is demonstrated by the data in table 3, below, in example 10, which discloses the ability of such compound samples to inhibit SCD biological activity. Alternatively, the usual values for the compounds to treat conditions and diseases may be established in industry standard animal models in order to demonstrate the effectiveness of the compounds in treating obesity, diabetes or elevated triglyceride or cholesterol levels or in improving glucose tolerance. Such models include Zucker obese fa/fa rats (available from Harlan Sprague Dawley, Inc. (Indianapolis, Indiana)) or Zucker diabetic fatty rats (ZDF/GmiCrl-fa/fa) (available from Charles River Laboratories (Montre al, Quebec)).

The present invention also relates to pharmaceutical compositions containing the novel compounds disclosed herein. In one embodiment, the invention relates to compositions comprising an amount of a compound of the invention, which is effective to modulate triglyceride levels or treat diseases and disorders of lipid metabolism when administered to an animal, preferably a mammal, most preferably a human patient, in a pharmaceutically acceptable carrier. In one embodiment of the composition, the patient has an elevated lipid level, such as elevated triglycerides or cholesterol, prior to administration of the compound of the invention and in the presence of an amount of the compound of the invention effective to lower the lipid level.

The compounds of the present invention are inhibitors of delta-9 desaturase and are useful in the treatment of diseases and conditions of humans or other organisms, including all those caused by abnormal delta-9 desaturase biological activity, or which can be ameliorated by modulation of delta-9 desaturase biological activity.

As defined herein, SCD-mediated diseases or disease states include, but are not limited to, cardiovascular disease, dyslipidemia (including, but not limited to, disorders of triglyceride serum levels, hypertriglyceridemia, VLDL, HDL, LDL, fatty acid desaturation index (e.g., 18: 1/18: 0 fatty acids or ratios of fatty acids as defined elsewhere herein), cholesterol and total cholesterol, hypercholesterolemia, and 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, or diseases or disease states associated therewith, the compounds of the invention will raise the HDL levels and/or lower the levels of triglycerides and/or lower LDL or non-HDL cholesterol levels in a patient.

SCD-mediated diseases or conditions also include metabolic syndrome (including but not limited to dyslipidemia, obesity and insulin resistance, hypertension, microalbuminemia, hyperuricemia, and hypercoagulable state of blood), syndrome X, diabetes, insulin resistance, impaired 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 disorders. In a preferred embodiment, the compounds of the present invention are useful for the treatment of diabetes and obesity.

The term "metabolic syndrome" as used herein is a recognized clinical term used to describe disease states including a combination of type II diabetes, impaired glucose tolerance, insulin resistance, hypertension, obesity, increased abdominal circumference, hypertriglyceridemia, low HDL, hyperuricemia, blood hypercoagulable state, and/or microalbuminemia.

SCD-mediated diseases or conditions also include fatty liver, hepatic steatosis, hepatitis, nonalcoholic steatohepatitis (NASH), alcoholic hepatitis, acute fatty liver, fatty liver in pregnancy, drug-induced hepatitis, erythropoietic protoporphyrinemia (erythrohepatosis), iron overload disorders, hereditary hemochromatosis, liver fibrosis, cirrhosis, liver cancer, and conditions associated therewith.

SCD-mediated diseases or disease states also include, but are not limited to, primary hypertriglyceridemia, secondary hypertriglyceridemia associated with another disorder or disease, hypertriglyceridemia of unknown etiology or unspecified etiology, or a disease or disease state associated therewith. Such as hyperlipoproteinemia, familial histiocytosis reticulocytosis, lipoprotein lipase deficiency, apolipoprotein deficiency (e.g. ApoCII deficiency or ApoE deficiency) and the like.

SCD-mediated diseases or conditions also include disorders of polyunsaturated fatty acid (PUFA) abnormalities or skin disorders including, but not limited to, eczema, acne, psoriasis, keloid scarring or prevention, diseases associated with mucosal production or mucosal secretions such as monounsaturated fatty acids, wax esters, and the like.

SCD-mediated diseases or conditions also include, but are not limited to, inflammation, sinusitis, asthma, pancreatitis, osteoarthritis, rheumatoid arthritis, cystic fibrosis, and premenstrual syndrome.

SCD-mediated diseases or conditions also include, but are not limited to, cancer, neoplasia, malignancy, metastasis, tumor (benign or malignant), carcinogenesis, liver cancer, and the like, or a disease or condition associated therewith.

SCD-mediated diseases or conditions also include conditions in which an increase in lean body mass or lean muscle mass is desired, such as where enhanced function through muscle building is desired. Also included herein are myopathies and lipid myopathies, such as carnitine palmitoyl transferase deficiency (CPT I or CPT II). These treatments may be used in the human and animal husbandry industries, including administration to cattle, swine, avian livestock or any other animal to reduce triglyceride production and/or provide a leaner meat product and/or a healthier animal.

SCD-mediated diseases or conditions also include neurological diseases, psychiatric diseases, multiple sclerosis, ocular diseases, and immune disorders, or diseases or conditions associated therewith.

SCD-mediated diseases or conditions also include viral diseases or infections, or diseases or conditions associated therewith, including but not limited to all positive strand RNA viruses, coronaviruses, SARS viruses, SARS-associated coronaviruses, togaviruses, picornaviruses, coxsackieviruses, yellow fever viruses, flaviviridae, alphaviruses (togaviridae), including rubella viruses, eastern equine encephalitis viruses, western equine encephalitis viruses, venezuelan equine encephalitis viruses, Sindbis viruses (Sindbis viruses), Semliki forest viruses (Semliki forest viruses), Chikungunya viruses (Chikungunya viruses), O 'nyong' nyong viruses, ross river viruses, mayalo viruses (Mayaro viruses), alphaviruses; astroviridae, which includes astrovirus, human astrovirus; caliciviridae, which include porcine herpes simplex virus, Norwalk virus (Norwalk virus), Calicivirus (calicivirus), bovine calicivirus, porcine calicivirus, hepatitis E; coronaviridae including coronavirus, SARS virus, avian infectious bronchitis virus, bovine coronavirus, canine coronavirus, feline infectious peritonitis virus, human coronavirus 299E, human coronavirus OC43, murine hepatitis virus, porcine epidemic diarrhea virus, porcine hemagglutinating encephalomyelitis virus, porcine transmissible gastroenteritis virus, rat coronavirus, turkey coronavirus, rabbit coronavirus, berney virus, brigda virus (Breda virus); flaviviridae, including hepatitis c virus, West Nile virus (West Nile virus), yellow fever virus, st lous encephalitis virus, dengue genus, hepatitis g virus, epidemic encephalitis b virus, Murray Valley encephalitis virus (Murray Valley encephalitis virus), middle european tick-borne encephalitis virus, far east tick-borne encephalitis virus, kosarou forest virus (Kyasanur for estvirus), skip virus (Louping virus), Powassan virus (Powassan virus), ompask hemorrhagic fever virus (ompsk hemorrhagic fever virus), Kumilinge virus, Absetarov anhalova virus, ileus virus, roci encephalitis virus (rociensis virus), Langat virus, diarrhea virus, swine virus, reo genus, rienya genus, tyaovirus, rinokay genus, rinokra virus; picornaviridae, which includes coxsackie a virus, rhinovirus, hepatitis a virus, encephalomyocarditis virus, mengo virus (Mengovirus), ME virus, human poliovirus 1, coxsackie B virus; POTYVIRIDAE (POTYVIRIDAE), which includes potyvirus, lolium mosaic virus (Rymovirus), barley yellow mosaic virus (Bymovirus). In addition, diseases or disease states caused by or associated with hepatitis virus, hepatitis B virus, hepatitis C virus, Human Immunodeficiency Virus (HIV), and the like may also be mentioned. Treatable viral infections include viral infections (hepatitis or HIV) in which the virus uses an RNA intermediate as part of the replication cycle; in addition, diseases or disease states caused by or associated with RNA negative strand viruses such as influenza and parainfluenza viruses are also possible.

The compounds identified in the present specification achieve inhibition of desaturation of various fatty acids (e.g., C9-C10 desaturation of stearoyl-CoA) by delta-9 desaturases, such as stearoyl-CoA desaturase 1(SCD 1). These compounds likewise inhibit the production of various fatty acids and their downstream metabolites. This can lead to the accumulation of stearoyl-coa or palmitoyl-coa and other upstream precursors of various fatty acids; this may create a negative feedback loop, causing the fatty acid metabolism to be totally altered. Any of these results may ultimately bring about the overall therapeutic benefit provided by these compounds.

Generally, a successful SCD-inhibiting therapeutic will meet some or all of the following criteria. The oral availability is equal to or greater than 20%. The efficacy of the animal model is less than about 2mg/Kg, 1mg/Kg or 0.5mg/Kg and the target human dose is 50 to 250mg/70Kg, although doses outside this range are also acceptable ("mg/Kg" refers to milligrams of compound per kilogram of body weight of the subject to which it is administered). The therapeutic index (or the ratio of toxic to therapeutic dose) should be greater than 100. Potency (by IC)₅₀Values expressed) should be below 10 μ M, preferably below 1 μ M and most preferably below 50 nM. IC (integrated circuit) ₅₀("inhibitory concentration-50%") is a measure of the amount of compound required to achieve 50% inhibition of SCD activity in a specific time period in an SCD biological activity assay. Any method of determining SCD enzyme activity, preferably mouse or human SCD enzyme activity, can be used to assay the activity of a compound used in the methods of the present invention in inhibiting said SCD activity. Compounds of the invention exhibit IC in a 15 minute microsomal assay₅₀Preferably less than 10. mu.M, less than 5. mu.M, less than 2.5. mu.M, less than 1. mu.M, less than 750nM, less than 500nM, less than 250nM, less than 100nM, less than 50nM and most preferably less than 20 nM. The compounds of the invention may exhibit reversible inhibition (i.e., competitive inhibition) and preferably do not inhibit iron binding proteins. The desired administration should preferably not exceed about once or twice a day or not more than the number of meals.

Identification of compounds of the invention as SCD inhibitors can be readily accomplished using the SCD enzyme and microsomal assay procedures described in brown et al, supra.

Table 3 in example 10 below provides data on the SCD inhibition effect of the compounds of the present invention tested in this assay. In particular, table 3 presents the percent SCD activity remaining at 10 μ M of the compound of the present invention in the assay.

These results provide the basis for the analysis of the structure-activity relationship (SAR) between test compounds and SCD. Certain R groups tend to provide more effective inhibitory compounds. One of the tools of the skilled person is the SAR analysis, which can now be used to identify preferred embodiments of the compounds of the invention for use as therapeutic agents.

Other methods of testing the compounds disclosed herein are also readily available to those skilled in the art. Thus, in addition to this, the contact can also be achieved in vivo. In one such embodiment, the contacting in step (a) is accomplished by administering the chemical agent to an animal having a disorder associated with Triglyceride (TG) or Very Low Density Lipoprotein (VLDL), and subsequently detecting plasma triglyceride levels in the animal, thereby identifying a therapeutic agent that can be used to treat the disorder associated with Triglyceride (TG) or Very Low Density Lipoprotein (VLDL). In this embodiment, the animal can be a human, such as a human patient suffering from the condition and in need of treatment for the condition.

In a specific embodiment of this in vivo method, said alteration of SCD1 activity in said animal is a decrease in activity, preferably wherein said SCD1 modulator does not substantially inhibit the biological activity of a delta-5 desaturase, delta-6 desaturase or fatty acid synthetase.

Model systems for compound evaluation may include, but are not limited to, the use of liver microsomes, such as from mice maintained on a high carbohydrate diet, or from human donors including people with obesity. Immortalized cell lines such as HepG2 (from human liver), MCF-7 (from human breast cancer) and 3T3-L1 (from mouse adipocytes) can also be used. Primary cell lines such as mouse primary hepatocytes may also be used to test the compounds of the invention. When whole animals are used, mice used as a source of primary hepatocytes may also be used, wherein the mice are maintained on a high carbohydrate diet to increase SCD activity in microsomes and/or to increase plasma triglyceride levels (i.e., a ratio of 18: 1/18: 0); alternatively, mice fed a normal diet or mice with normal triglyceride levels can be used. A mouse model using transgenic mice designed for hypertriglyceridemia can also be used as a mouse phenotyping database. Rabbits and hamsters can also be used as animal models, in particular animal models expressing CETP (cholesterol ester transfer protein).

Another suitable method for determining the in vivo efficacy of a compound of the invention is to indirectly measure its effect on SCD enzyme inhibition by measuring the desaturation index of an individual after administration of said compound. As used herein, "desaturation index" refers to the ratio of product to substrate of the measured SCD enzyme from a given tissue sample. Three different equations 18: 1 n-9/18: 0 (oleic acid to stearic acid) can be used; 16: 1 n-7/16: 0 (palmitoleic acid to palmitic acid); and/or 16: 1n-7+ 18: 1 n-7/16: 0 (measuring the ratio of total reaction product to 16: 0 substrate for 16: 0 desaturation). The desaturation index is measured mainly in liver or plasma triglycerides, but can also be measured in other selected lipid fractions from various tissues. In general, the desaturation index is a tool for plasma lipid profiling.

A number of human diseases and conditions are the result of aberrant SCD1 biological activity and may be ameliorated by modulating SCD1 biological activity using the therapeutic agents of the present invention.

Inhibition of SCD expression may also affect the fatty acid composition of membrane phospholipids and the production or levels of triglycerides and cholesterol esters. The fatty acid composition of phospholipids ultimately determines membrane fluidity, while the effect on the combination of triglycerides and cholesterol esters can affect lipoprotein metabolism and obesity.

In carrying out the practice of the present invention, it will of course be understood that reference to particular buffers, media, reagents, cells, culture conditions and the like are not intended to be limiting, but should be taken to include reference to all relevant materials which one of ordinary skill in the art would recognize as being of interest or value in the particular context of this patent. For example, it is often possible to use one buffer system or medium in place of another and achieve similar, but not identical, results. Those skilled in the art have sufficient knowledge and methodology regarding the system to be able to make such substitutions without undue experimentation to best achieve the objectives achieved using the methods and operations disclosed herein.

Pharmaceutical compositions and administration of the invention

The invention also relates to pharmaceutical compositions containing the compounds of the invention disclosed herein. In one embodiment, the present invention relates to a pharmaceutical composition comprising an amount of a compound of the present invention, which is effective to modulate triglyceride levels or treat diseases and disorders of lipid metabolism associated with dyslipidemia, in a pharmaceutically acceptable carrier when administered to an animal, preferably a mammal, most preferably a human patient. In an embodiment of such a composition, the patient has an elevated lipid level, such as elevated triglycerides or cholesterol, prior to administration of the compound of the invention and in the presence of an amount of the compound of the invention effective to reduce the lipid level.

As used herein, a pharmaceutical composition contains a pharmaceutically acceptable carrier, including any suitable diluent or excipient, which includes any pharmaceutical agent that does not itself induce the production of antibodies harmful to the individual receiving the composition, and which can be administered without undue toxicity. Pharmaceutically acceptable carriers include, but are not limited to, liquids such as water, saline, glycerol, and ethanol, among others. There is a detailed discussion of pharmaceutically acceptable carriers, diluents, and other excipients in REMINGTON' S pharmaceutical excipients (Mack pub.

One skilled in the art would know how to determine an appropriate dosage of a compound for treating the diseases and disorders of interest herein. Therapeutic doses are generally identified by studies on dose ranges in humans based on preliminary evidence from animal studies. The dosage must be sufficient to achieve the desired therapeutic effect without causing unwanted side effects to the patient. For animals, the preferred dosage range is 0.001mg/Kg to 10,000mg/Kg, including 0.5mg/Kg, 1.0mg/Kg and 2.0mg/Kg, although dosages outside this range are also acceptable. The dosing regimen may be once or twice daily, although greater or lesser numbers of administrations are also satisfactory.

Those skilled in the art are also familiar with determining methods of administration (oral, intravenous, inhalation, subcutaneous, etc.), dosage forms, appropriate pharmaceutical excipients, and other materials relevant to the delivery of a compound to a subject in need thereof.

In another use of the invention, the compounds of the invention may be used for in vitro or in vivo studies as exemplary agents for the comparison to find other compounds that are also useful for the treatment or prevention of the various diseases disclosed herein.

Preparation of the Compounds of the general formula (I)

It is to be understood that in the following description combinations of substituents and/or variants of the formulae are also permissible only if such combinations of substituents and/or variants of the formulae lead to stable compounds.

It will be appreciated by those skilled in the art that in the methods described below, the functional groups of the intermediate compounds may need to be protected by suitable protecting groups. These functional groups include hydroxyl, amino, mercapto and carboxylic acid. Suitable hydroxy protecting groups include trialkylsilyl or diaralkylsilyl groups (e.g.tert-butyldimethylsilyl, tert-butyldiphenylsilyl or trimethylsilyl), tetrahydropyranyl, benzyl and the like. Suitable amino, amidino and guanidino protecting groups include tert-butoxycarbonyl, benzyloxycarbonyl and the like. Suitable thiol protecting groups include-C (O) -R "(where R" is alkyl, aryl or aralkyl), p-methoxybenzyl, trityl and the like. Suitable carboxylic acid protecting groups include alkyl, aryl or aralkyl esters.

Protecting groups may be introduced or removed according to standard techniques well known to those skilled in the art and described herein.

The use of protecting Groups is described in detail in Green, t.w. and p.g.m. Wutz, Protective Groups in organic synthesis (1999), 3rd ed., Wiley. The protecting group may also be a polymer resin, such as Wang resin or 2-chlorotrityl chloride resin.

It will also be appreciated by those skilled in the art that while these protected derivatives of the compounds of the present invention may not possess pharmaceutical activity, they are administered to a mammal and thereafter metabolized in vivo to produce the compounds of the present invention which possess pharmaceutical activity. Accordingly, such derivatives may be described as "prodrugs". All prodrugs of the compounds of the present invention are included within the scope of the present invention.

The following reaction scheme illustrates a method for preparing the compounds of the present invention. Unless otherwise indicated, the various R groups in the reaction schemes have the same meaning as described in the summary of the invention above. It is understood that these compounds can be prepared by similar methods or by methods known to those skilled in the art. In general, starting components are obtained from sources such as Sigma Aldrich, Lancaster Synthesis, Inc., Maybrid, Matrix Scientific, TCI, and Fluorochem USA, or are synthesized according to sources known to those skilled in the art (see, e.g., Advanced Organic Chemistry: Reactions, Mechanisms, and structures), 5th edition (Wiley, December 2000)), or are prepared as described herein.

The following reaction scheme 1 illustrates the preparation of the compounds of the present invention by solid phase techniques.

Reaction scheme 1-solid phase Process

Experimental procedures-solid phase method

Preferred synthetic schemes use solid phase synthesis and Kan^TMA reactor. Kan^TMThe reactor is a rigid vessel with a meshed outer wall. A single compound is synthesized in each reactor, each containing a unique micro rfid and a real solid phase resin.

The Kan reactor is designed to be loaded with solid phase resin beads and Rf tags. The synthesis was performed by flowing the reactants through the outer mesh wall of Kan. The synthesis was performed using common laboratory glassware and equipment for heating, cooling, mixing, etc.

There are 3 different sizes of Kan reactors with AccuTag systems that can be used interchangeably, namely micro kans, MiniKans and macro kans. Typically, about 30-300mg of the most commercially available resin is loaded into the Kan, leaving enough room for the resin to swell and remain loose in the Kan.

The synthesis was performed by flowing the reactants through the cell walls of Kan. With the AccuTag system, the Kan reactor allows practically any synthetic chemistry to be carried out using bulk solid phase resins and conventional laboratory glassware.

Kan is made of high grade polypropylene and polypropylene mesh outer wall. Kan was filled with solid phase resin and radio frequency identification before use in synthesis. One skilled in the art of Kan technology can select a suitable size of Kan.

Further information on the Irori Kan technology can be obtained from Discovery Partners, inc. of www.discoverypartners.com.

All reagents, amines and carboxylic acids required to perform the following syntheses are available from widely available commercial sources.

Kans 1(12 Kans) containing indole resin (90 mg per Kan, 0.9mmol/g) was suspended in anhydrous trimethyl orthoformate (40 mL). Amine 2(10mmol, 10eq) was added and the reaction was shaken at room temperature for 16 h. Sodium cyanoborohydride (1.3g, 20eq) was added and the reaction was shaken at room temperature for 1 hour. Aqueous acetic acid (3.2mL, 8% v/v) was added slowly and the reaction was shaken at room temperature for 3 hours. MiniKans 3 was washed with MeOH and DCM alternately for 4 cycles and dried in vacuo.

Kans containing 3 from 7 reactions (84 MiniKans total) were suspended in anhydrous DMF (250 mL). 6-Chloronicotinic acid (11.2g, 10eq), diisopropylethylamine (25mL, 20eq) and HATU (26.2g, 10eq) were added and the reaction was shaken at room temperature for 24 h. Kans 5 was washed with MeOH and DCM alternately for 4 cycles and dried in vacuo.

Kans containing 5 was suspended in dry N-methylpyrrolidone (250 mL). Piperazine 6(12.0g, 20eq) and diisopropylethylamine (49mL, 40eq) were added and the reaction mixture was heated at 80 ℃ for 48 hours. MiniKans containing 7 was washed with 4 cycles of alternating MeOH and DCM and dried in vacuo.

After sorting, Kans containing 7 (12 Kans) were suspended in anhydrous DMF (40 mL). Carboxylic acid 8(10mmol, 10eq), diisopropylethylamine (3.5mL, 20eq) and HATU (3.8g, 10eq) were added and the reaction was shaken at room temperature for 24 h. Kans containing 9 was washed with 5 cycles of alternating MeOH and DCM and dried in vacuo.

Kans containing 9 (3 Kans) were treated with 20% TFA/DCM (9mL) for 2 hours at room temperature. Pyridylpiperazine 10 was obtained and purified by HPLC.

The solid phase process is used to prepare the compounds of the invention. Examples of amines and carboxylic acids used in solid phase processes for producing compounds of the present invention are provided in tables 1 and 2 below.

TABLE 1 examples of amines

TABLE 2 examples of carboxylic acids

Another synthetic scheme for preparing the compounds of the present invention includes a convergent liquid phase process, as illustrated in scheme 2 below. For example, the acid chloride 12 may be prepared from the corresponding acid 11 by reaction with thionyl chloride under conditions known to those skilled in the art or the acid chloride 12 may be purchased from commercial sources such as aldrich chemical Co. Reaction of 12 with piperazine 13 under conditions known to those skilled in the art yields an amide bond of 14, where the protecting group can be removed in an acidic medium such as trifluoroacetic acid in dichloromethane to yield compound 15 under conditions known to those skilled in the art. Alternatively, 6-chloronicotinic acid (16) is converted to its chloride 17 under conditions known to those skilled in the art, and the chloride 17 is then combined with amine 18 to provide nicotinamide 19. The combination of 15 and 19 provides the final product 20 under conditions known to those skilled in the art.

Reaction scheme 2

Alternatively, the compounds of the present invention are prepared according to the synthetic methods described in the following reaction scheme 3. Methyl 6-chloronicotinate (21) is combined with piperazine 22 under conditions known to those skilled in the art to provide compound 23, which compound 23 is then reacted with acid chloride 12 under conditions known to those skilled in the art to produce compound 24. The methyl ester is hydrolyzed using a base such as lithium hydroxide under conditions known to those skilled in the art to give an acid 25, which acid 25 is reacted with the amine 18 under conditions known to those skilled in the art to provide the final product 26.

Reaction scheme 3

Alternatively, the compounds of the present invention are prepared according to the synthetic procedures described in the following reaction scheme 4,wherein R is⁴is-OCH₃or-OH. The 2, 6-dichloronicotinic acid 27 is converted to its ester 28 under conditions known to those skilled in the art, wherein the chloro group at the 2-position is then substituted with a methoxy group under conditions known to those skilled in the art to yield compound 29. Conjugation to piperazine under conditions known to those skilled in the art 29 produces compound 30, which compound 30 reacts with acid chloride 12 under conditions known to those skilled in the art to produce compound 31. After hydrolysis, acid 32 is reacted with amine 18 under conditions known to those skilled in the art to produce nicotinamide 33. The methyl group in compound 33 is removed by using a Lewis acid such as trimethylsilicon iodide generated in situ under conditions known to those skilled in the art to provide compound 34.

Reaction scheme 4

All reagents and reaction conditions used in these syntheses are well known to those skilled in the art and may be obtained from common commercial sources. The compounds of the present invention are prepared according to the methods described above or by the methods disclosed in the following experiments using known starting materials and experimental parameters by a person skilled in the art. In addition, the compounds of the present invention can be prepared by methods disclosed in U.S. Pat. No. 6,677,452, which is incorporated herein by reference in its entirety, by those skilled in the art.

All compounds of the invention prepared above and below in the form of the free base or free acid may be converted into their pharmaceutically acceptable salts by treatment with a suitable inorganic or organic base or acid. Salts of the compounds prepared herein can be converted to their free bases or free acids by standard techniques.

The following specific examples are provided as guidance to aid in the practice of the invention, but are not meant to limit the scope of the invention.

Example 1

N- (2-cyclopropylethyl) -6- [4- (5-fluoro-2-trifluoromethylbenzoyl) piperazin-1-yl ] nicotinamide

To 6- [4- (5-fluoro-2-trifluoromethylbenzoyl) piperazin-1-yl ]To a solution of nicotinic acid (0.100g, 0.25mmol) and 1-hydroxybenzotriazole hydrate (0.041g, 0.30mmol) in dichloromethane (20mL) was added 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide (0.047g, 0.30mmol) and ethyldiisobutylamine (0.065g, 0.50 mmol). The resulting mixture was stirred at room temperature for 15 minutes, then a solution of 2-cyclopropylethylamine (0.021g, 0.25mmol) in 5mL of dichloromethane was added. The reaction mixture was stirred at room temperature for 24 hours, then diluted with dichloromethane (50 mL). The organic phase was washed with water, brine solution, anhydrous Na₂SO₄Dried and concentrated in vacuo to yield a white solid. Purify the white solid using column chromatography (2: 1, ethyl acetate: hexanes) to give the title compound as a white solid (0.087g, 75% yield);

¹H NMR(CDCl₃，300MHz)δ8.52(d，J＝2.4Hz，1H)，7.92(dd，J＝2.4，6.6Hz，1H)，7.72(d，J＝7.8Hz，1H)，7.61-7.5(m，2H)，7.34(d，J＝7.5Hz，1H)，6.62(d，J＝9Hz，1H)，6.14(t，J＝5.1Hz，1H)，3.98-3.92(m，1H)，3.87-3.78(m，1H)，3.75-3.66(m，2H)，3.6-3.47(m，4H)，3.29-3.25(m，2H)，1.52-1.45(m，2H)，0.72-0.65(m，1H)，0.49-0.43(m，2H)，0.1-0.04(m，2H)。¹³C NMR(CDCl₃75MHz) delta 167.5, 165.7, 159.7, 147.1, 136.9, 134.4, 134.3, 132.3, 129.3, 127.4, 126.74, 126.68, 126.62, 120.0, 105.8, 46.5, 44.4, 41.3, 40.1, 34.3, 8.6, 4.1(2 peaks). MS (ES +) M/z447(M + 1).

Example 2

N- (2-cyclobutylethyl) -6- [4- (5-fluoro-2-trifluoromethylbenzoyl) piperazin-1-yl ] nicotinamide

The title compound was obtained as a white solid (0.053g, yield 44%) according to the procedure described in example 1;

¹H NMR(CDCl₃，300MHz)：δ8.51-8.50(m，1H)，7.94-7.90(m，1H)，7.75-7.7(m，1H)，7.21-7.19(m，1H)，7.07-7.04(m，1H)，6.63(d，J＝9Hz，1H)，5.94(t，J＝5.5Hz，1H)，3.96-3.89(m，1H)，3.87-3.77(m，1H)，3.75-3.68(m，2H)，3.65-3.58(m，2H)，3.37-3.27(m，4H)，2.38-2.28(m，1H)，2.12-1.98(m，2H)，1.94-1.73(m，3H)，1.7-1.58(m，3H)。¹³C NMR(CDCl₃，75MHz)：δ165.9，165.6，162.5，159.5，146.9，137.1，136.95，129.6，129.5，129.48，129.42，125.0，121.4，120.1，116.7，116.4，114.9，114.6，105.99，46.5，44.5，41.4，38.2，36.5，33.85，28.3，18.7。MS(ES+)：m/z479.1(M+1)。

Example 3

N- (3-cyclopropyl-propyl) -6- [4- (5-fluoro-2-trifluoromethylbenzoyl) -piperazin-1-yl ] nicotinamide

The title compound was obtained as a white solid (0.086g, yield 77%) according to the procedure described in example 1;

¹H NMR(CDCl₃，300MHz)δ8.53(s，1H)，7.94-7.9(m，1H)，7.74-7.7(m，1H)，7.21-7.18(m，1H)，7.07-7.03(m，1H)，6.61(d，J＝8.7Hz，1H)，6.18(t，J＝5.4Hz，1H)，3.97-3.58(m，6H)，3.46-3.39(m，2H)，3.29-3.26(m，2H)，1.72-1.63(m，2H)，1.28-1.21(m，2H)，0.70-0.61(m，1H)，0.43-0.37(m，2H)，0.01-0.04(m，2H)。¹³C NMR(CDCl₃，75MHz)δ165.9，165.7，162.4，159.5，147.2，136.9，129.5，129.5，129.4，129.35，128.6，124.95，123.1，122.7，121.3，120.1，116.6，116.3，114.8，114.5，105.8，46.4，44.3，41.3，39.6，31.9，29.5，10.4，4.4。MS(ES+)m/z479.0(M+1)。

example 4

6- [4- (5-fluoro-2-trifluoromethylbenzoyl) piperazin-1-yl ] -N- (4-methylpentyl) -nicotinamide

The title compound was obtained as a white solid (0.075g, 66% yield) as described in example 1;

¹H NMR(CDCl₃，300MHz)δ 8.52(s，1H)，7.94-7.91(m，1H)，7.72-7.7(m，1H)，7.21-7.18(m，1H)，7.06-7.04(m，1H)，6.62(d，J＝9Hz，1H)，6.02(br.t，1H)，3.98-3.55(m，6H)，3.43-3.34(m，2H)，3.3-3.26(m，2H)，1.62-1.48(m，3H)，1.25-1.18(m，2H)，0.86(d，J＝6.6Hz，6H)。¹³CNMR(CDCl₃，75MHz)δ165.9，165.7，162.5，159.5，147.1，137.02，129.6，129.5，129.4，129.38，128.6，127.6，124.5，122.7，121.4，120.1，117.7，116.6，116.4，114.8，114.5，105.8，46.4，44.4，41.3，40.1，36.0，27.7，27.5，22.4。MS(ES+)：m/z481.1(M+1)。

example 5

N- (3, 3-dimethylbutyl) -6- [4- (5-fluoro-2-trifluoromethylbenzoyl) piperazin-1-yl ] -nicotinamide

The title compound was obtained as a white solid (0.085g, yield 76%) according to the procedure described in example 1;

¹H NMR(CDCl₃，300MHz)δ 8.52(s，1H)，7.93-7.89(m，1H)，7.75-7.7(m，1H)，7.24-7.18(m，1H)，7.06-7.03(m，1H)，6.61(d，J＝9Hz，1H)，5.94(br，1H)，3.98-3.75(m，2H)，3.75-3.66(m，2H)，3.63-3.56(m，2H)，3.48-3.35(m，2H)，3.32-3.23(m，2H)，1.51-1.46(m，2H)，0.93(s，9H)。¹³C NMR(CDCl₃，75MHz)δ165.9，165.6，162.5，159.5，147.2，136.9，129.6，129.5，129.4，129.37，128.6，124.96，123.2，122.3，120.1，116.6，116.3，114.8，114.5，105.8，46.4，44.3，43.1，41.3，36.5，29.8，29.3。MS(ES+)m/z481.0(M+1)。

example 6

N- (2-Cyclopropylethyl) -6- [4- (2-trifluoromethylbenzoyl) -piperazin-1-yl ] -nicotinamide

Reacting 6- [4- (2-trifluoromethylbenzoyl) -piperazin-1-yl]A mixture of nicotinic acid (280mg, 0.738mmol), diisopropylethylamine (0.19mL, 1.1mmol), 1-hydroxybenzotriazole hydrate (130mg, 0.96mmol) and EDCI (0.19mL, 1.1mmol) in dichloromethane (5mL) was stirred for 15 min and 2-cyclopropylethylamine (70mg, 0.82mmol) was added. After stirring at room temperature for 10 min, the reaction mixture was diluted with dichloromethane (50mL), water, saturated NaHCO ₃Washed with brine and dried (anhydrous Na)₂SO₄) And concentrated. Purification by flash chromatography on silica gel (ethyl acetate) afforded N- (2-cyclopropylethyl) -6- [4- (2-trifluoromethylbenzoyl) -piperazin-1-yl]-nicotinamide (264mg, 80%).

¹HNMR：(400MHz，CDCl₃)δ 8.52(d，J＝1.9，1H)，7.94(dd，J＝1.9，8.7Hz，1H)，7.73(d，J＝9.2Hz，1H)，7.63(t，J＝8.5Hz，1H)，7.56(t，J＝8.5Hz，1H)，7.37(d，J＝8.7Hz，1H)，6.62(d，J＝9.2Hz，1H)，6.14(br，1H)，4.02-3.27(m，10H)，1.52(q，J＝6.7Hz，2H)，0.78-0.70(m，1H)，0.53-0.48(m，2H)，0.13-0.08(m，2H)。MS(ES+)m/z 447.2(M+1)。

Example 7

N- (2-Cyclopropylethyl) -2-methoxy-6- (4- (2-trifluoromethylbenzoyl) piperazin-1-yl ] nicotinamide

A. To a solution of 2, 6-dichloronicotinic acid (5.0g, 26mmol) in MeOH (100mL) was added SOCl₂(0.1 mL). The reaction mixture was heated to reflux overnight. The solvent was removed by evaporation. The residue was dissolved in ethyl acetate and taken up with saturated NaHCO₃And a brine wash; using anhydrous Na₂SO₄Dried and concentrated to give methyl 2, 6-dichloronicotinate (5.37g, 100%);

¹HNMR：(300MHz，CDCl₃)δ 8.13(d，J＝8.1Hz，1H)，7.33(d.J＝8.1Hz，1H)，3.94(s，3H)。

B. a solution of methyl 2, 6-dichloronicotinate (2.39g, 11.6mmol) and NaOMe (800mg, 14.06mmol) in THF (15mL) was stirred at room temperature for 3 days. By adding 10mL of 10% NH₄The reaction mixture was quenched with Cl solution and extracted with ether. Using anhydrous Na₂SO₄The combined organic layers were dried and concentrated to provide an inseparable mixture (1.7g) containing methyl 6-chloro-2-methoxynicotinate.

C. Dissolving the above crude material in CH₃CN (30ml), then piperazine (3.0g, 34.8mmol) was added. The reaction mixture was heated to reflux overnight. Acetonitrile was removed by evaporation to give crude 2-methoxy-6-piperazin-1-yl-nicotinic acid methyl ester (1.82 g). Et was added to the residue in dichloromethane (20mL) ₃N (1mL, 7.17mmol) and CoolCooling to 0 ℃. 2-Trifluoromethylbenzoic acid chloride (0.6mL, 4.05mmol) was added. The reaction mixture was stirred at room temperature for 2 hours, diluted with ethyl acetate and washed with water; with anhydrous Na₂SO₄Dried and concentrated. The residue was purified by silica gel chromatography to give methyl 2-methoxy-6- (4- (2-trifluoromethylbenzoyl) piperazin-1-yl) nicotinate (1.46g, 30% yield after 3 steps);

¹HNMR(300MHz，CDCl₃)δ8.04(d，J＝8.7 Hz，1H)，7.72(d，J＝7.8 Hz，1H)，7.61(dd，J＝7.5，7.8 Hz，1H)，7.53(dd，J＝7.5，7.8Hz，1H)，7.34(d，J＝7.8Hz，1H)，6.14(d，J＝8.7HZ，1H)，4.00-3.59(m，12H)，3.29-3.26(m，2H)。MS(ES⁺)m/z 446.0(M+Na)。

D. to a solution of methyl 2-methoxy-6- (4- (2-trifluoromethylbenzoyl) piperazin-1-yl) nicotinate (1.2g, 2.83mmol) in THF (30mL) and water (10mL) was added lithium hydroxide hydrate (476mg, 11.34 mmol). The reaction mixture was heated to reflux for 8 hours. The THF was removed by evaporation. The residue was neutralized with 5% HCl solution and extracted with ethyl acetate. The combined organic phases were washed with water and brine; using anhydrous Na₂SO₄Dried and concentrated to give 2-methoxy-6- (4- (2-trifluoromethylbenzoyl) piperazin-1-yl) nicotinic acid (1.08g, 96%);

¹HNMR(300MHz，CDCl₃)δ 8.19(d，J＝8.7Hz，1H)，7.73(d，J＝7.8Hz，1H)，7.62(dd，J＝7.5，7.8Hz，1H)，7.53(dd，J＝7.5，7.8Hz，1H)，7.34(d，J＝7.8 Hz，1H)，6.29(d，J＝8.7Hz，1H)，4.13-3.57(m，9H)，3.36-3.28(m，2H)；MS(ES⁺)m/z432.1(M+1)。

E. to a solution of 2-methoxy-6- (4- (2-trifluoromethylbenzoyl) piperazin-1-yl) nicotinic acid (440mg, 1.07mmol) in dichloromethane (20mL) was added diisopropylethylamine (0.5mL, 2.8mmol), 1-hydroxybenzotriazole hydrate (215mg, 1.5mmol) and EDCI (0.28mL, 1.5 mmol). The resulting mixture was stirred for 15 minutes; cyclopropylethylamine (110mg, 1.2mmol) was then added. After stirring for 20 hours, dichloromethane (100 m) is used L) dilution of the reaction mixture, washing with water, brine and use of anhydrous Na₂SO₄Dried and concentrated. Purification by flash chromatography on silica gel (ethyl acetate) and recrystallization from ethyl acetate and hexanes afforded N- (2-cyclopropylethyl) -2-methoxy-6- (4- (2-trifluoromethylbenzoyl) piperazin-1-yl) nicotinamide (340mg, 67%); m.p.49-51 ℃.

¹H NMR(300MHz，CDCl₃)δ8.32(d，J＝8.7Hz，1H)，7.80(t，J＝4.8Hz，1H)，7.72(d，J＝7.8Hz，1H)，7.63-7.50(m，2H)，7.34(d，J＝7.5Hz，1H)，6.25(d，J＝8.7Hz，1H)，3.96-3.80(m，4H)，3.74-3.66(m，2H)，3.56-3.47(m，4H)，3.29-3.26(m，2H)，1.49(q，J＝6.0 Hz，2H)，0.76-0.66(m，1H)，0.49-0.43(m，2H)，0.12-0.07(m，2H)；¹³C NMR(CDCl₃，75MHz)δ167.5，164.3，160.0，158.1，143.5，134.5，132.3，129.3，127.2，126.8，104.9，99.1，53.4，46.5，44.5，44.4，41.3，39.8，34.4，8.9，4.1。MS(ES⁺)m/z 477.4(M+1)。

Example 8

2-oxo-6- [4- (2-trifluoromethylbenzoyl) -piperazin-1-yl ] -1, 2-dihydro-pyridine-3-carboxylic acid (2-cyclopropylethyl) amide

To N- (2-Cyclopropylethyl) -2-methoxy-6- (4- (2-trifluoromethylbenzoyl) piperazin-1-yl) nicotinamide (270mg, 0.56mmol) and sodium iodide (332mg, 2.2mmol) in CH at 0 deg.C₃CN (5mL) mixture was added chlorotrimethylsilane (0.28mL, 2.2mmol) and 1 drop of water. The reaction mixture was stirred at room temperature overnight. The reaction was quenched by the addition of 5mL MeOH at 0 deg.C and concentrated. The residue was purified using silica gel chromatography (ethyl acetate) and recrystallized from ethyl acetate and hexane to give N- (2-cyclopropylethyl) -2-hydroxy-6- (4- (2-trifluoromethylbenzoyl) piperazin-1-yl) nicotinamide (79mg, 30%);

¹H NMR(300MHz，CDCl₃)δ8.02(d，J＝8.7Hz，1H)，7.80(t，J＝7.5Hz，1H)，7.64(t，J＝7.5Hz，1H)，7.50(d，J＝7.5Hz，1H)，5.92(br，1H)，3.75-3.05(m，10H)，1.34(q，J＝1.34Hz，2H)，0.71-0.57(m，1H)，0.44-0.28(m，2H)，0.08-0.03(m，2H)；MS(ES⁺)m/z 463.1(M+1)。

example 9

Representative compounds of the present invention are prepared according to the synthetic methods described in reaction schemes 1 and 2 above, or by using appropriately substituted starting materials in a manner analogous to the methods disclosed herein, or by methods known to those skilled in the art:

6- [4- (2-ethylbutanoyl) piperazin-1-yl ] -n- (3-phenylpropyl) nicotinamide; 423.3(M + 1);

6- [4- (4-methyl-hexanoyl) piperazin-1-yl ] -n- (3-phenylpropyl) nicotinamide; 423.2(M + 1);

6- [4- (2-ethylbutanoyl) -3-methylpiperazin-1-yl ] -n- (3-phenylpropyl) nicotinamide; 37.3(M + 1);

6- [4- (2-phenylcyclopropanecarbonyl) piperazin-1-yl ] -n- (3-phenylpropyl) nicotinamide; 469.1(M + 1);

6- [4- (3-cyclohexylpropionyl) piperazin-1-yl ] -n- (3-methylbutyl) nicotinamide; 415.3(M + 1);

6- [4- (2-cyclohexylacetyl) piperazin-1-yl ] -n-hexyl-nicotinamide; 415.2(M + 1);

n-butyl-6- [4- (3-cyclohexylpropionyl) piperazin-1-yl ] nicotinamide; 401.2(M + 1);

6- [4- (2-cyclohexylacetyl) piperazin-1-yl ] -n-pentyl-nicotinamide; 401.2(M + 1);

6- [4- (3-cyclohexylpropionyl) piperazin-1-yl ] -n-pentyl-nicotinamide; 415.2(M + 1);

n- [2- (3-chlorophenyl) ethyl ] -6- [4- (3-cyclohexylpropionyl) piperazin-1-yl ] nicotinamide; 483.1(M + 1);

n- [2- (3-chlorophenyl) ethyl ] -6- [4- (2-cyclohexylacetyl) piperazin-1-yl ] nicotinamide 469.1(M + 1);

n-butyl-6- [4- (2-mercapto-benzoyl) piperazin-1-yl ] nicotinamide; 447.2(M + 1);

n- (3-methylbutyl) -6- [4- (2-o-tolylacetyl) piperazin-1-yl ] nicotinamide; 409.2(M + 1);

6- {4- [2- (2, 4-dimethylphenyl) -acetyl ] -piperazin-1-yl } -N- (3-methylbutyl) nicotinamide; 409.2(M + 1);

6- [4- (2-bromo-benzoyl) piperazin-1-yl ] -n- (3-ethoxy-propyl) nicotinamide; 475.1(M + 1);

6- {4- [2- (2-chloro-6-fluorophenyl) -acetyl ] -piperazin-1-yl } -N- (3-methylbutyl) nicotinamide; 447.1(M + 1);

n- (3-methylbutyl) -6- [4- (2-trifluoromethylbenzoyl) piperazin-1-yl ] nicotinamide; 449.0(M + 1);

n- (3-methylbutyl) -6- [4- (2-trifluoromethylbenzoyl) piperazin-1-yl ] nicotinamide hydrochloride; 448.7 (M-HCl);

n- (3-methylbutyl) -4-trifluoromethyl-6- [4- (2-trifluoromethylbenzoyl) piperazin-1-yl ] nicotinamide; 517.3(M + 1);

2-chloro-5-fluoro-N- (3-methylbutyl) -6- [4- (2-trifluoromethylbenzoyl) piperazin-1-yl ] nicotinamide; 501.1(M + 1);

2-chloro-N- (3-methylbutyl) -6- [4- (2-trifluoromethylbenzoyl) piperazin-1-yl ] nicotinamide; 483.1(M + 1);

n- (3-methylbutyl) -6- [ 3-oxo-4- (2-trifluoromethylbenzyl) piperazin-1-yl ] nicotinamide; 449.2(M + 1);

6- [4- (2, 5-dichloro-benzoyl) piperazin-1-yl ] -n- (3-imidazol-1-ylpropyl) nicotinamide; 487.0(M + 1);

6- [4- (2, 4-dichloro-benzoyl) piperazin-1-yl ] -n- (3-imidazol-1-ylpropyl) nicotinamide; 487.1(M + 1);

6- [4- (2-bromo-5-methoxy-benzoyl) piperazin-1-yl ] -n- (3-phenylpropyl) nicotinamide; 539.0(M + 1);

6- [4- (2-bromo-benzoyl) piperazin-1-yl ] -n- [2- (3H-imidazol-4-yl) ethyl ] nicotinamide; 483.0(M + 1);

n- [2- (3-chlorophenyl) ethyl ] -6- [4- (2, 4-dichloro-benzoyl) piperazin-1-yl ] nicotinamide; 519.1(M + 3);

6- [ 2-oxo-4- (2-trifluoromethylbenzoyl) piperazin-1-yl ] -n- (3-phenylpropyl) nicotinamide; 511.2(M + 1);

n- (3-methylbutyl) -6- [ 2-oxo-4- (2-trifluoromethylbenzoyl) piperazin-1-yl ] nicotinamide; 463.1(M + 1);

6- [4- (3-methyl-3H-114-thiophene-2-carbonyl) piperazin-1-yl ] -n-pentyl-nicotinamide; 401.1(M + 1);

n- [2- (3-chlorophenyl) ethyl ] -6- [4- (3-methyl-thiophene-2-carbonyl) piperazin-1-yl ] nicotinamide; 469.1(M + 1);

6- {4- [2- (4-chlorophenyl) propionyl ] -piperazin-1-yl } -N- (3-methylbutyl) nicotinamide; 443.0(M + 1);

6- [4- (2-phenylbutyryl) piperazin-1-yl ] -n- (3-phenylpropyl) nicotinamide; 471.3(M + 1);

n-pentyl-6- [4- (2-phenylcyclopropanecarbonyl) piperazin-1-yl ] nicotinamide; 421.2(M + 1);

n- (3-methylbutyl) -6- [4- (naphthalene-1-carbonyl) piperazin-1-yl ] nicotinamide; 431.5(M + 1);

n- (3-methylbutyl) -6- [4- (naphthalene-1-carbonyl) piperazin-1-yl ] nicotinamide; 431.2(M + 1);

N- [2- (3-chlorophenyl) ethyl ] -6- [4- (2-phenylcyclopropanecarbonyl) piperazin-1-yl ] nicotinamide; 489.2(M + 1);

6- [5- (2-ethylbutanoyl) -2, 5-diaza-bicyclo [2.2.1] hept-2-yl ] -n- (3-phenylpropyl) nicotinamide; 435.3(M + 1);

6- [4- (2-ethylbutyl) piperazin-1-yl ] -n- (3-phenylpropyl) nicotinamide; 409.3(M + 1);

6- [4- (butane-1-sulfonyl) piperazin-1-yl ] -n- (3-phenylpropyl) nicotinamide; 444.9(M + 1);

4- [5- (3-phenylpropylcarbamoyl) pyridin-2-yl ] -piperazine-1-carboxylic acid butanamide; 424.3(M + 1);

n- (3-ethoxy-propyl) -6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] nicotinamide;

n- (3-butoxy-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-methyl-butyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n-butyl-6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-ethylbutyryl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

N- (2-ethylsulfanyl-ethyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- (4-pentanoyl-piperazin-1-yl) -N-pentyl-nicotinamide;

n-hexyl-6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (1, 3-dimethylbutyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (2-methyl-butyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-ethylbutyryl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

n-butyl-6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

n- (3-isopropoxy-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

n- (2-methyl-butyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-dimethylamino-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- [2- (3-chlorophenyl) -1-methylethyl ] -6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -nicotinamide

N- [2- (3-chlorophenyl) -ethyl ] -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-ethylbutyryl) -piperazin-1-yl ] -nicotinamide;

6- (4-pentanoyl-piperazin-1-yl) -N- (4-phenyl-butyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- (4-pentanoyl-piperazin-1-yl) -N- (3-phenyl-propyl) nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- (4-pentanoyl-piperazin-1-yl) -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-ethylbutyryl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

N- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- (4-pentanoyl-piperazin-1-yl) -N-phenethyl-nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

n-butyl-6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

n-pentyl-6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

N- (3-butoxy-propyl) -6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide

N- (2-ethylsulfanyl-ethyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

N- (3-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

N- (1-methyl-3-phenyl-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

n-butyl-6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

n-butyl-6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-butoxy-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

N- (3-ethoxy-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

N- (3-methoxy-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-butoxy-propyl) -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (3-butoxy-propyl) -6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N-butyl-nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

n- (1-methyl-butyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

n- (1-methyl-butyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

n-butyl-6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

n-hexyl-6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

n-hexyl-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

n- (2-methyl-butyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

N- (3-ethoxy-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-methyl-butyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

N- (3-ethoxy-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n-butyl-6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

N- (2-ethylsulfanyl-ethyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

N- (1-methyl-butyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (2-cyclopropyl-ethyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-cyclopropyl-ethyl) -6- [4- (5-fluoro-2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-cyclopropyl-ethyl) -2-hydroxy-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-cyclobutyl-ethyl) -6- [4- (5-fluoro-2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-cyclopropyl-propyl) -6- [4- (5-fluoro-2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (5-fluoro-2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -N- (4-methyl-pentyl) -nicotinamide;

N- (3, 3-dimethylbutyl) -6- [4- (5-fluoro-2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-2-phenyl-ethyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-2-phenyl-ethyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n-phenethyl-6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2, 5-dichloro-phenyl) -acetyl ] -piperazin-1-yl } -N- (2-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-fluoro-4-methyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- [2- (3-chloro-phenyl) -ethyl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (2-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (5-phenyl-pentyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- [2- (3-chloro-phenyl) -ethyl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-difluoro-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

n-phenethyl-6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

n-phenethyl-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

N- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

N- (3-dimethylamino-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

n-pentyl-6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

N-hexyl-6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

n-butyl-6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

n- (2-methyl-butyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

N- (2-methyl-butyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n-hexyl-6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- {4- [2- (2-chloro-pyridin-3-yl) -acetyl ] -piperazin-1-yl } -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

N- (3-phenyl-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

N- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-ethoxy-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-dimethylamino-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-ethoxy-propyl) -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-ethoxy-propyl) -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n-butyl-6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-dimethylamino-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- {4- [2- (4-chloro-phenyl) -propionyl ] -piperazin-1-yl } -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (2-methylbutyl) -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-methylbutyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-methoxy-propyl) -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (2-methylbutyl) -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (1-methylbutyl) -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (2-methylbutyl) -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-isopropoxy-propyl) -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N-hexyl-nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (1-methylbutyl) -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (1, 3-dimethylbutyl) -nicotinamide;

N-butyl-6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (1, 3-dimethylbutyl) -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-methoxy-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-isopropoxy-propyl) -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N-pentyl-nicotinamide;

n- (3-butoxy-propyl) -6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N-hexyl-nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-methoxy-propyl) -nicotinamide;

n-hexyl-6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (4-phenyl-butyl) -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (1-methylbutyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N-pentyl-nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N-hexyl-nicotinamide;

n-butyl-6- {4- [2- (4-chloro-phenyl) -propionyl ] -piperazin-1-yl } -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N-pentyl-nicotinamide;

n-hexyl-6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (1, 3-dimethylbutyl) -nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-dimethylamino-propyl) -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

N- (3-butoxy-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-isopropoxy-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N-phenethyl-nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-phenyl-propyl) -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N-phenethyl-nicotinamide;

n- (3-phenyl-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- [2- (3-chloro-phenyl) -ethyl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-phenyl-propyl) -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- {4- [2- (4-chloro-phenyl) -propionyl ] -piperazin-1-yl } -nicotinamide;

N- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (4-phenyl-butyl) -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-phenyl-propyl) -nicotinamide;

n-phenethyl-6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (4-phenyl-butyl) -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N-phenethyl-nicotinamide;

n-phenethyl-6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

N- (tetrahydrofuran-2-ylmethyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

N-phenethyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

N- (1-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide; and

n- (2-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide.

Example 10

The compounds of the invention can be readily identified as SCD inhibitors using the SCD enzyme and microsomal assays described in published PCT patent application WO 01/62954 to Brownlie et al. Briefly, mouse or human liver microsomes (induced for SCD1 expression and containing cytochrome b)₅And cytochrome b₅Reductase) and NADH as well as the compound of the invention were suspended in buffer and the reaction was initiated by adding 0.025mM tritiated stearoyl-coa. The ligand is tritiated only at the C9 and C10 positions. The reaction is allowed to proceed at room temperature for 5 to 20 minutes and is interrupted by the addition of acid. Activated carbon is then added, mixed and centrifuged to separate the labelled substrate from the labelled water. The supernatant fraction was then tested for radioactivity using liquid scintillation counting. This can be used as a measure of delta-9 desaturase activity.

When tested using this assay, data for the inhibitory effect of the compounds of the invention on SCD are provided in table 3 below, which represents the percentage of SCD activity remaining at 10 μ M of the test compound in the indicated assay. Using the bulk bench test tube method, test compounds were pre-incubated with test compounds for 15 minutes at room temperature and desaturated for 15 minutes at room temperature in 100 μ g of mouse liver microsomes.

TABLE 3 SCD inhibitory Activity of selected Compounds

Compound (I)	Activity% 10. mu.M	Mol. weight
			6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl]-N- (2-ethylsulfanyl-ethyl) -nicotinamide	1.4	516.15
N- (3-phenyl-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl]-nicotinamide	1.3	458.13
			6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl]-N-pentyl-nicotinamide	0.7	496.21

Compound (I)	Activity% 10. mu.M	Mol. weight
			6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl]-N- (3-methylbutyl) -nicotinamide	1.3	492.12
6- [4- (2-bromo-benzoyl) -piperazin-1-yl]-N- (3-butoxy-propyl) -nicotinamide	0.8	448.21
			N-butyl-6- [4- (2-ethylbutanoyl) -piperazin-1-yl]-nicotinamide	2.0	448.14
N- (3-butoxy-propyl) -6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl]-nicotinamide	0.7	482.19
			N- (3-methyl-butyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl]-nicotinamide	3.2	442.27
6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl]-N- (1-methyl-3-phenyl-propyl) -nicotinamide	2.7	434.19
			6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl]-N-phenethyl-nicotinamide	1.1	496.14
6- [4- (2-ethylbutanoyl) -piperazin-1-yl]-N- (3-methylbutyl) -nicotinamide	1.7	448.21
			6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl]-N-pentyl-nicotinamide	1.2	482.13
N- (1, 3-dimethylbutyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl]-nicotinamide	1.8	458.13
			6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl]-N- (2-ethylsulfanyl-ethyl) -nicotinamide	1.4	448.14
6- [4- (2-bromo-benzoyl) -piperazin-1-yl]-N- (3-methoxy-propyl) -nicotinamide	1.2	462.22

Compound (I)	Activity% 10. mu.M	Mol. weight
			6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl]-N- (1-methylbutyl) -nicotinamide	2.1	430.24
6- [4- (2-bromo-benzoyl) -piperazin-1-yl]-N- (3-ethoxy-propyl) -nicotinamide	1.0	537.5
			N- (1-methyl-3-phenyl-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl]-nicotinamide	3.4	469
6- [4- (2-phenyl-butyryl) -piperazin-1-yl]-N- (3-phenyl-propyl) -nicotinamide	3.6	445.4
			N- (2-ethylsulfanyl-ethyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ]-nicotinamide	1.8	470.6
N- (3-phenyl-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl]-nicotinamide	3.9	408.5

All U.S. patents, U.S. patent application publications, U.S. patent 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 illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not to be restricted except in light of the attached claims.

Claims (61)

1. A method of treating an SCD-mediated disease or condition in a mammal, wherein said method comprises administering to said mammal in need thereof a therapeutically effective amount of a compound of formula (I):

wherein:

m is 1, 2 or 3;

n is 1, 2, 3 or 4;

p is 2, 3 or 4;

v is-C (O) -, -S (O) -or-S (O)₂-；

R¹Is hydrogen, alkyl, alkenyl, aryl, heteroaryl, aralkyl, aralkenyl or cycloalkyl;

R²selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

R³selected from hydrogen, -R⁹-OR⁸、-R⁹-N(R⁸)₂An alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

Each R⁴Independently hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl, cyano, nitro, -R⁹-OR⁸、-R⁹-N(R⁸)₂or-S (O)_tR¹⁰(wherein t is 0, 1 or 2);

each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

or, an R⁵And one R⁶May together form a linear or branched alkylene bridge;

each R⁷Independently a straight or branched alkylene chain or alkenylene chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloAn alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl group;

each R⁹Independently a direct bond or a straight or branched alkylene or alkenylene chain; and

R¹⁰is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

the compound is a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a tautomer;

or a pharmaceutically acceptable salt thereof, a prodrug thereof, a solvate thereof, or a polymorph thereof.

2. The method of claim 1, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2 or 3;

v is-C (O) -or-S (O)₂-；

R¹Is hydrogen or alkyl;

R²selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

R³is alkyl, alkenyl or-R⁹-N(R⁸)₂；

Each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸；

Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

or, an R⁵And one R⁶May together form a linear or branched alkylene bridge;

each R⁷Independently a straight or branched alkylene chain or alkenylene chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

each R⁹Independently a direct bond or a linear or branched alkenylene chain; and

R¹⁰Is alkyl, aryl or aralkyl.

3. The method of claim 2, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl;

R³is an alkyl group;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl;

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl;

each R⁷Is a straight or branched alkylene chain;

each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, and aralkyl; and

R¹⁰is alkyl, aryl or aralkyl.

4. The method of claim 3, wherein the compound of formula (I) is a compound wherein:

m is 1;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2) or alkyl;

R³is an alkyl group;

R⁴is hydrogen;

R⁵is hydrogen;

each R⁶Is hydrogen;

R⁷is a straight or branched alkylene chain;

R⁸is hydrogen or alkyl; and

R¹⁰is alkyl, aryl or aralkyl.

5. The method of claim 4, wherein the compound of formula (I) is selected from the group consisting of:

n- (3-ethoxy-propyl) -6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-methyl-butyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n-butyl-6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-ethylbutyryl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- (4-pentanoyl-piperazin-1-yl) -N-pentyl-nicotinamide;

n-hexyl-6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

N- (1-methyl-butyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (1, 3-dimethylbutyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (2-methyl-butyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-ethylbutyryl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

n-butyl-6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

n- (3-isopropoxy-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

n- (2-methyl-butyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

N- (1, 3-dimethylbutyl) -6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- (4-pentanoyl-piperazin-1-yl) -nicotinamide; and

n- (3-dimethylamino-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide.

6. The method of claim 2, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2 or 3;

v is-C (O) -or-S (O)₂-；

R¹Is hydrogen or alkyl;

R²selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, and optionally substituted heteroaralkenyl;

R³Is alkyl or-R⁹-N(R⁸)₂；

Each R⁴Independently hydrogen, alkyl, halo or haloalkyl; and

each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

or, an R⁵And one R⁶May together form a linear or branched alkylene bridge;

R⁷is a direct bond; and

each R⁸Independently hydrogen or alkyl.

7. The method of claim 6, wherein the compound of formula (I) is a compound wherein:

m is 1;

n is 1;

p is 2 or 3;

v is-C (O) -or-S (O)₂-；

R¹Is hydrogen or alkyl;

R²selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;

R³is alkyl or-R⁹-N(R⁸)₂；

R⁴Is hydrogen, alkyl, halo or haloalkyl; and

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl;

or, an R⁵And one R⁶May together form a methylene bridge;

R⁷is a direct bond; and

each R⁸Independently hydrogen or alkyl.

8. The method of claim 7, wherein the compound of formula (I) is selected from the group consisting of:

6- [4- (2-ethylbutanoyl) piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (4-methyl-hexanoyl) piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- [2- (3-chlorophenyl) -1-methylethyl ] -6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-ethylbutyryl) -piperazin-1-yl ] -nicotinamide;

6- (4-pentanoyl-piperazin-1-yl) -N- (4-phenyl-butyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- (4-pentanoyl-piperazin-1-yl) -N- (3-phenyl-propyl) -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- (4-pentanoyl-piperazin-1-yl) -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-ethylbutyryl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- (4-pentanoyl-piperazin-1-yl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- (4-pentanoyl-piperazin-1-yl) -N-phenethyl-nicotinamide;

6- [4- (2-ethylbutanoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-ethylbutanoyl) - [1, 4] diazepin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (2-ethylbutanoyl) -3-methyl-piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [5- (2-ethylbutanoyl) -2, 5-diaza-bicyclo [2.2.1] hept-2-yl ] -n- (3-phenyl-propyl) -nicotinamide;

6- [4- (butane-1-sulfonyl) piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

4- [5- (3-phenyl-propylcarbamoyl) pyridin-2-yl ] -piperazine-1-carboxylic acid butanamide.

9. The method of claim 1, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²Selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

R³is optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl;

each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸；

Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

each R⁷Independently a straight or branched alkylene chain or alkenylene chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

R⁹is a direct bond or is a straight or branched alkylene chain; and

R¹⁰is alkyl, aryl or aralkyl.

10. The method of claim 9, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl;

R³is optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl;

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl;

each R⁷Is a straight or branched alkylene chain;

each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, and aralkyl; and

R¹⁰is alkyl, aryl or aralkyl.

11. The method of claim 10, wherein the compound of formula (I) is a compound wherein:

m is 1;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2) or alkyl;

R³is optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl;

R⁴is hydrogen;

R⁵is hydrogen;

each R⁶Is hydrogen;

R⁷is a straight or branched alkylene chain;

R⁸is hydrogen or alkyl; and

R¹⁰independently an alkyl, aryl or aralkyl group.

12. The method of claim 11, wherein the compound of formula (I) is selected from the group consisting of:

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

n-butyl-6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

n-pentyl-6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

N- (3-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide; and

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide.

13. The method of claim 9, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted The heteroarylalkyl group of (a) and an optionally substituted heteroarylalkenyl group;

R³is optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl; and

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

14. The method of claim 13, wherein the compound of formula (I) is a compound wherein:

m is 1;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;

R³is optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl;

R⁴is hydrogen, alkyl, halo or haloalkyl;

R⁵independently hydrogen, oxo, alkyl, halo or haloalkyl; and

each R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

15. The method of claim 14, wherein the compound of formula (I) is selected from the group consisting of:

6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

N- (4-phenyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (3-cyclohexyl-propionyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide; and

6- [4- (2-cyclohexyl-acetyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide.

16. The method of claim 1, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

R³Is an optionally substituted aryl group;

each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸；

Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

each R⁷Independently a straight or branched alkylene chain or alkenylene chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

R⁹is a direct bond or is a straight or branched alkylene chain; and

R¹⁰is alkyl, aryl or aralkyl.

17. The method of claim 16, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl;

R³is an optionally substituted aryl group;

each R⁴Independently is hydrogen, alkyl, halo, haloalkyl or-R⁹-OR⁸；

Each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl;

each R⁷Is a straight or branched alkylene chain;

Each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, and aralkyl;

R⁹is a direct bond or is a straight or branched alkylene chain; and

R¹⁰is alkyl, aryl or aralkyl.

18. The method of claim 17, wherein the compound of formula (I) is a compound wherein:

a compound, wherein:

m is 1 or 2;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 01 or 2), alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl;

R³is an optionally substituted aryl group;

each R⁴Independently is hydrogen, halo, haloalkyl or-R⁹-OR⁸；

R⁵Is hydrogen;

each R⁶Is hydrogen;

R⁷is a straight or branched alkylene chain;

R⁸is hydrogen or alkyl;

R⁹is a direct bond or is a straight or branched alkylene chain; and

R¹⁰is alkyl, aryl or aralkyl.

19. The method of claim 18, wherein the compound of formula (I) is selected from the group consisting of:

n-butyl-6- [4- (2-mercapto-benzoyl) piperazin-1-yl ] nicotinamide;

n- (3-methylbutyl) -6- [4- (2-o-tolylacetyl) piperazin-1-yl ] nicotinamide;

6- {4- [2- (2, 4-dimethyl-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-methylbutyl) nicotinamide;

6- [4- (2-bromo-benzoyl) piperazin-1-yl ] -N- (3-ethoxypropyl) nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-methylbutyl) nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

n-butyl-6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

n-butyl-6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-butoxy-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

an amine;

n- (3-ethoxy-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

N-butyl-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

N-pentyl-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-butoxy-propyl) -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (3-butoxy-propyl) -6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N-butyl-nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

n- (1-methyl-butyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

n- (1-methyl-butyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

N-butyl-6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

n-butyl-6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

n-hexyl-6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

N-hexyl-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

n- (2-methyl-butyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

N-butyl-6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-methyl-butyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -4-trifluoromethyl-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

2-chloro-5-fluoro-N- (3-methylbutyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

N- (3-ethoxy-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n-butyl-6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

N- (2-ethylsulfanyl-ethyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

N- (3-butoxy-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

2-chloro-N- (3-methylbutyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-cyclopropyl-ethyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-cyclopropyl-ethyl) -2-methoxy-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-cyclopropyl-ethyl) -6- [4- (5-fluoro-2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

2-oxo-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -1, 2-dihydro-pyridine-3-carboxylic acid (2-cyclopropylethyl) amide;

N- (2-cyclopropyl-ethyl) -2-hydroxy-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (2-cyclobutyl-ethyl) -6- [4- (5-fluoro-2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-cyclopropyl-propyl) -6- [4- (5-fluoro-2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (5-fluoro-2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -N- (4-methyl-pentyl) -nicotinamide;

n- (3, 3-dimethylbutyl) -6- [4- (5-fluoro-2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide.

20. The method of claim 16, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2; v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, and optionally substituted heteroaralkenyl;

R³is an optionally substituted aryl group;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl; and

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

21. The method of claim 20, wherein the compound of formula (I) is a compound wherein:

m is 1;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;

R³is an optionally substituted aryl group;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl;

R⁵is hydrogen, oxo, alkyl, halo or haloalkyl; and

each R⁶Independently hydrogen, alkyl, halo or haloalkyl.

22. The method of claim 21, wherein the compound of formula (I) is selected from the group consisting of:

6- [4- (2, 5-dichloro-benzoyl) piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) ethyl ] -nicotinamide;

n- (1-methyl-2-phenyl-ethyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

N- (1-methyl-2-phenyl-ethyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

N- (1-methyl-3-phenyl-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (naphthalene-1-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-naphthalen-2-yl-acetyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

N-phenethyl-6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2, 5-dichloro-phenyl) -acetyl ] -piperazin-1-yl } -N- (2-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-fluoro-4-methyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- [2- (3-chloro-phenyl) -ethyl ] -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (2-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (5-phenyl-pentyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- [2- (3-chloro-phenyl) -ethyl ] -nicotinamide;

N- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

n-phenethyl-6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

n-phenethyl-6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2-bromo-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dimethyl-benzoyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-bromo-5-methoxy-benzoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (3-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

N- [2- (3-chlorophenyl) -ethyl ] -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (2, 4-dichloro-benzoyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

6- [4- (2, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (4-trifluoromethyl-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3, 5-dichloro-benzoyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2, 3, 4, 5-tetrafluoro-benzoyl) -piperazin-1-yl ] -nicotinamide;

6- [ 2-oxo-4- (2-trifluoromethyl-benzoyl) piperazin-1-yl ] -N- (3-phenylpropyl) -nicotinamide;

n- (3-methylbutyl) -6- [ 2-oxo-4- (2-trifluoromethyl-benzoyl) piperazin-1-yl ] -nicotinamide.

23. The method of claim 1, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

R³is optionally substituted heteroaryl, optionally substituted heteroaralkyl or optionally substituted heteroaralkenyl;

each R⁴Independently hydrogen, alkyl, alkenyl, halo, haloalkyl or aryl;

each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

each R⁷Independently a straight or branched alkylene chain or alkenylene chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl; and

R¹⁰is alkyl, aryl or aralkyl.

24. The method of claim 23, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl;

R³is optionally substituted heteroaryl, optionally substituted heteroaralkyl or optionally substituted heteroaralkenyl;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl;

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl;

each R⁷Is a straight or branched alkylene chain;

each R⁸Independently of each other is hydrogen,Alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl and aralkyl; and

R¹⁰is alkyl, aryl or aralkyl.

25. The method of claim 24, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl;

R³is optionally substituted heteroaryl, optionally substituted heteroaralkyl or optionally substituted heteroaralkenyl;

each R⁴Independently hydrogen, halo or haloalkyl;

R⁵is hydrogen;

each R⁶Is hydrogen;

R⁷is a straight or branched alkylene chain;

R⁸Is hydrogen or alkyl; and

R¹⁰is alkyl, aryl or aralkyl.

26. The method of claim 25, wherein the compound of formula (I) is selected from the group consisting of:

6- [4- (3-methyl-3H-114-thiophene-2-carbonyl) piperazin-1-yl ] -N-pentyl-nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-ethoxy-propyl) -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-methylbutyl) -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-isopropoxy-propyl) -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-methoxy-propyl) -nicotinamide;

n-pentyl-6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N-hexyl-nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (1, 3-dimethylbutyl) -nicotinamide;

n-butyl-6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (2-methylbutyl) -nicotinamide;

n- (2-methyl-butyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (1-methylbutyl) -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

N- (3-isopropoxy-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

n-hexyl-6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide; and

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-dimethylamino-propyl) -nicotinamide.

27. The method of claim 23, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen orAn alkyl group;

R²selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, and optionally substituted heteroaralkenyl;

R³is optionally substituted heteroaryl, optionally substituted heteroaralkyl or optionally substituted heteroaralkenyl;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl; and

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

28. The method of claim 27, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;

R³is optionally substituted heteroaryl, optionally substituted heteroaralkyl or optionally substituted heteroaralkenyl;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl;

R⁵Is hydrogen, oxo, alkyl, halo or haloalkyl; and

each R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

29. The method of claim 21, wherein the compound of formula (I) is selected from the group consisting of:

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (3-methyl-thiophene-2-carbonyl) piperazin-1-yl ] nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- {4- [2- (2-chloro-pyridin-3-yl) -acetyl ] -piperazin-1-yl } -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -N-phenethyl-nicotinamide;

6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (3-methyl-thiophene-2-carbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- (3-imidazol-1-yl-propyl) -nicotinamide;

6- [4- (2-chloro-pyridine-3-carbonyl) -piperazin-1-yl ] -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide.

30. The method of claim 1, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -

R¹Is hydrogen or alkyl;

R²selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

R³is an optionally substituted aralkyl group or an optionally substituted aralkenyl group;

each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸；

Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

each R⁷Independently a straight or branched alkylene chain or alkylideneAn alkenyl chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

R⁹Is a direct bond or is a straight or branched alkylene chain; and

R¹⁰is alkyl, aryl or aralkyl.

31. The method of claim 30, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl;

R³is an optionally substituted aralkyl group or an optionally substituted aralkenyl group;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl;

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl;

each R⁷Is a straight or branched alkylene chain;

each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, and aralkyl; and

R¹⁰is alkyl, aryl or aralkyl.

32. The method of claim 31, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2) or alkyl;

R³is an optionally substituted aralkyl group or an optionally substituted aralkenyl group;

Each R⁴Independently hydrogen, halo, haloalkyl;

R⁵is hydrogen;

each R⁶Is hydrogen;

R⁷is a straight or branched alkylene chain;

R⁸is hydrogen or alkyl; and

R¹⁰is alkyl, aryl or aralkyl.

33. The method of claim 32, wherein the compound of formula (I) is selected from the group consisting of:

6- {4- [2- (4-chlorophenyl) propionyl ] -piperazin-1-yl } -N- (3-methylbutyl) nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-ethoxy-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-dimethylamino-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-ethoxy-propyl) -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-ethoxy-propyl) -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (3-methyl-pentanoyl) -piperazin-1-yl ] -N- (4-phenyl-butyl) -nicotinamide;

n-butyl-6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-dimethylamino-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- {4- [2- (4-chloro-phenyl) -propionyl ] -piperazin-1-yl } -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (2-methylbutyl) -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-methylbutyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-methoxy-propyl) -nicotinamide;

N- (1-methyl-butyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (2-methylbutyl) -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (1-methylbutyl) -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (2-methylbutyl) -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-isopropoxy-propyl) -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N-hexyl-nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (1-methylbutyl) -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (1, 3-dimethylbutyl) -nicotinamide;

n-butyl-6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

N- (1, 3-dimethylbutyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (1, 3-dimethylbutyl) -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

n- (3-ethoxy-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-methoxy-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-isopropoxy-propyl) -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N-pentyl-nicotinamide;

n- (3-butoxy-propyl) -6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N-hexyl-nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-methoxy-propyl) -nicotinamide;

n-hexyl-6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (4-phenyl-butyl) -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (1-methylbutyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N-pentyl-nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N-hexyl-nicotinamide;

n-butyl-6- {4- [2- (4-chloro-phenyl) -propionyl ] -piperazin-1-yl } -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (2-ethylsulfanyl-ethyl) -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N-pentyl-nicotinamide;

N-hexyl-6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (1, 3-dimethylbutyl) -nicotinamide;

6- [4- (naphthalene-2-carbonyl) -piperazin-1-yl ] -N-pentyl-nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-dimethylamino-propyl) -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -nicotinamide;

n- (3-methoxy-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (2-methyl-butyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide; and

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-isopropoxy-propyl) -nicotinamide.

34. The method of claim 30, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from optionally substituted aryl groups,Optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl and optionally substituted heteroaralkenyl;

R³is an optionally substituted aralkyl group or an optionally substituted aralkenyl group;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl; and

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

35. The method of claim 34, wherein the compound of formula (I) is a compound wherein:

m is 1 or 2;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;

R³Is an optionally substituted aralkyl group or an optionally substituted aralkenyl group;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl; and

R⁵is hydrogen, oxo, alkyl, halo or haloalkyl; and

each R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

36. The method of claim 35, wherein the compound of formula (I) is selected from the group consisting of:

6- [4- (2-phenyl-butyryl) piperazin-1-yl ] -N- (3-phenyl-propyl) nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N-phenethyl-nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-phenyl-propyl) -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N-phenethyl-nicotinamide;

n- (3-phenyl-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- [2- (3-chloro-phenyl) -ethyl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-phenyl-propyl) -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- {4- [2- (4-chloro-phenyl) -propionyl ] -piperazin-1-yl } -nicotinamide;

n- [2- (3-chlorophenyl) -ethyl ] -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n-phenethyl-6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-phenyl-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (4-phenyl-butyl) -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-phenyl-propyl) -nicotinamide;

n-phenethyl-6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (1-methyl-3-phenyl-propyl) -nicotinamide;

N- (4-phenyl-butyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (4-phenyl-butyl) -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N-phenethyl-nicotinamide;

n-phenethyl-6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (4-chlorophenyl) -propionyl ] -piperazin-1-yl } -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

N- (4-phenyl-butyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- (tetrahydrofuran-2-ylmethyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-o-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [3- (3, 4-difluoro-phenyl) -propionyl ] -piperazin-1-yl } -N- (3-imidazol-1-yl-propyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-phenyl-butyryl) -piperazin-1-yl ] -nicotinamide;

n- (3-imidazol-1-yl-propyl) -6- [4- (2-p-tolyl-acetyl) -piperazin-1-yl ] -nicotinamide;

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide; and

6- {4- [2- (2-chloro-6-fluoro-phenyl) -acetyl ] -piperazin-1-yl } -N- [2- (3H-imidazol-4-yl) -ethyl ] -nicotinamide.

37. The method of claim 1, wherein the mammal is a human.

38. The method of claim 37, wherein the disease or condition is one associated with serum levels of triglycerides, VLDL, HDL, LDL, total cholesterol or the reverse process of cholesterol transport.

39. The method of claim 37, wherein the disease or condition is a disease or condition associated with serum triglyceride levels.

40. The method of claim 37, wherein the disease or condition is a disease or condition associated with serum cholesterol levels.

41. The method of claim 37, wherein the disease or condition is selected from the group consisting of type II diabetes, impaired glucose tolerance, insulin resistance, hypertension, obesity, hypertriglyceridemia, low HDL, lipidemia, dyslipidemia, microalbuminemia, hyperuricemia, a blood hypercoagulable state, hyperleptinemia, metabolic syndrome, and any combination thereof.

42. The method of claim 41, wherein the disease or condition is type II diabetes.

43. The method of claim 41, wherein the disease or condition is obesity.

44. The method of claim 41, wherein the disease or condition is dyslipidemia.

45. The method of claim 41, wherein the disease or condition is metabolic syndrome.

46. A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a therapeutically effective amount of a compound of formula (I):

wherein:

m is 1 to 3;

n is 1, 2, 3 or 4;

p is 2 or 3;

v is-C (O) -or-S (O)₂-；

R¹Is hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl or cycloalkyl;

R²selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

R³selected from hydrogen, -R⁹-OR⁸、-R⁹-N(R⁸)₂An alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

Each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸；

Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

or, an R⁵And one R⁶May together form a linear or branched alkylene bridge;

each R⁷Independently a straight or branched alkylene chain or alkenylene chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

each R⁹Independently a direct bond or a straight or branched alkylene or alkenylene chain; and

R¹⁰is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heteroCycloalkylalkyl, heteroaryl or heteroaralkyl;

the compound is a single stereoisomer, a mixture of stereoisomers, or a racemic mixture of stereoisomers;

or a pharmaceutically acceptable salt thereof, a prodrug thereof, a solvate thereof, or a polymorph thereof.

47. The pharmaceutical composition of claim 46, wherein the therapeutically effective amount of the compound of formula (I) is an amount effective to modulate the lipid level in a mammal when administered to said mammal.

48. The pharmaceutical composition of claim 47, wherein the lipid is a triglyceride.

49. The pharmaceutical composition of claim 47, wherein the lipid is cholesterol.

50. The pharmaceutical composition of claim 46, wherein the therapeutically effective amount of the compound of formula (I) is an amount effective to modulate HDL-cholesterol levels when administered to a mammal.

51. A method of treating a patient having, or preventing the development of, a disease or condition mediated by stearoyl-coa desaturase (SCD), wherein said method comprises administering to a patient having, or at risk of having, said disease or condition, a therapeutically effective amount of a compound that, when administered to said patient, inhibits SCD activity in the patient.

52. A compound of the general formula (I):

wherein:

m is 1, 2 or 3;

n is 1, 2, 3 or 4;

p is 2, 3 or 4;

v is-C (O) -, -S (O) -or-S (O)₂-；

R¹Is hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl or cycloalkyl;

R²selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

R³Selected from cycloalkyl substituted with one or more substituents independently selected from alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, -R⁹-OR⁸、-R⁹-N(R⁸)₂、-R⁹-C(O)R⁸、-R⁹-C(O)OR⁸、-R⁹-C(O)N(R⁸)₂、-R⁹-N(R⁸)C(O)OR¹⁰、-R⁹-N(R⁸)C(O)R¹⁰、-R⁹-N(R⁸)(S(O)_tR¹⁰) (wherein t is 1 or 2), -R⁹-S(O)_tOR¹⁰(wherein t is 1 or 2), -R⁹-S(O)_tR¹⁰(wherein t is 0, 1 or 2) and-R⁹-S(O)_tN(R⁸)₂(wherein t is 1 or 2);

each R⁴Independently hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl, cyano, nitro, -R⁹-OR⁸、-R⁹-N(R⁸)₂or-S (O)_tR¹⁰(wherein t is 0, 1 or 2);

each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

or, an R⁵And one R⁶May together form a linear or branched alkylene bridge;

each R⁷Independently a straight or branched alkylene chain or alkenylene chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

each R⁹Independently a direct bond or a straight or branched alkylene or alkenylene chain; and

R¹⁰is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

The compound is a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a tautomer;

or a pharmaceutically acceptable salt thereof, a prodrug thereof, a solvate thereof, or a polymorph thereof.

53. The compound of claim 52, wherein R³Is cyclopropyl substituted with optionally substituted aryl or optionally substituted heteroaryl.

54. The compound of claim 53, wherein;

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from hydrogen, -R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), an alkyl group, an alkenyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted aralkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted cycloalkylalkenyl group, an optionally substituted heterocyclic group, an optionally substituted heterocyclylalkyl group, an optionally substituted heterocyclylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heteroaralkyl group, and an optionally substituted heteroaralkenyl group;

each R⁴Independently is hydrogen, alkyl, alkenyl, halo, haloalkyl, aryl or-R⁹-OR⁸；

Each R⁵And R⁶Independently hydrogen, oxo, alkyl, alkenyl, halo, haloalkyl or aryl;

Each R⁷Independently a straight or branched alkylene chain or alkenylene chain;

each R⁸Independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;

R⁹is a direct bond or is a straight or branched alkylene chain; and

R¹⁰is alkyl, aryl or aralkyl.

55. The compound of claim 54, wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from the group consisting of optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, and optionally substituted heteroaralkenyl;

each R⁴Independently hydrogen, alkyl, halo or haloalkyl; to be provided withAnd

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl.

56. The compound of claim 55, wherein:

m is 1;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is optionally substituted aralkyl, optionally substituted heteroaralkyl or optionally substituted heterocyclylalkyl;

R³Is cyclopropyl substituted by phenyl;

R⁴is hydrogen, alkyl, halo or haloalkyl;

R⁵is hydrogen, oxo, alkyl, halo or haloalkyl; and

each R⁶Is hydrogen.

57. The compound of claim 56, selected from the group consisting of:

6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -N- (3-phenyl-propyl) -nicotinamide;

n- (4-phenyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-3-phenyl-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide

N-phenethyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -N- (tetrahydrofuran-2-ylmethyl) -nicotinamide;

n- [2- (3H-imidazol-4-yl) -ethyl ] -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide; and

n- (3-imidazol-1-yl-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide.

58. The compound of claim 54, wherein:

m is 1 or 2;

n is 1 or 2;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²is selected from-R⁷-OR⁸、-R⁷-N(R⁸)₂、-R⁷-S(O)_tR¹⁰(wherein t is 0, 1 or 2), alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted cycloalkylalkenyl;

Each R⁴Independently hydrogen, alkyl, halo or haloalkyl;

each R⁵And R⁶Independently hydrogen, oxo, alkyl, halo or haloalkyl;

each R⁷Is a straight or branched alkylene chain;

each R⁸Independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, and aralkyl; and

R¹⁰is alkyl, aryl or aralkyl.

59. The compound of claim 58, wherein:

m is 1;

n is 1;

p is 2;

v is-C (O) -;

R¹is hydrogen or alkyl;

R²selected from alkyl, -R⁷-OR⁸、-R⁷-N(R⁸)₂or-R⁷-S(O)_tR¹⁰(wherein t is 0);

R³is cyclopropyl substituted by phenyl;

R⁴is hydrogen;

R⁵is hydrogen;

each R⁶Is hydrogen;

R⁷is a linear or branched alkylene groupA chain;

R⁸is hydrogen or alkyl; and

R¹⁰is alkyl, aryl or aralkyl.

60. The compound of claim 59, selected from the group consisting of:

n- (3-ethoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (2-ethylsulfanyl-ethyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1, 3-dimethylbutyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

N- (3-methoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-butoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-pentyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-dimethylamino-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (3-isopropoxy-propyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n- (1-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-butyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide;

n-hexyl-6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide; and

n- (2-methyl-butyl) -6- [4- (2-phenyl-cyclopropanecarbonyl) -piperazin-1-yl ] -nicotinamide.

61. A method of treating a mammal having a disease or condition ameliorated by the inhibition of stearoyl-coa desaturase (SCD) activity, wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound that inhibits SCD activity in the mammal.