Substituted pyridones as inhibitors of poly(adp-ribose) polymerase (parp)

Abstract

The present invention relates to a series of 2,3,5-substituted pyridone derivatives of formula I: wherein R, R 1 , R 2 , R 3 and R 4 are as defined herein. This invention also relates to methods of making these compounds. The compounds of this invention are inhibitors of poly(adenosine 5′-diphosphate ribose) polymerase (PARP) and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases, including diseases associated with the central nervous system and cardiovascular disorders.

1 . A compound, or enantiomers, stereoisomers, or tautomers of said compound or pharmaceutically acceptable salts thereof, said compound having the structure shown in formula I: 
       
         
           
           
               
               
           
         
         wherein 
         R is hydrogen or C 1-6 alkyl; 
         R 1  is C 1-4 alkyl, C 1-4 alkenyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, wherein said alkyl or alkenyl is optionally substituted with one or more hydroxy or chlorine; 
         R 2  is Ar—Y, wherein
 Ar is substituted or unsubstituted aryl, aryloyl or heteroaryl wherein said substituents are selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkenyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, —NO 2 , —CH 2 NH 2 , —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —C(O)R 11 , —NHC(O)(C 1-4 alkyl), —SO 2 Cl, —SO 2 (C 1-4 alkyl), halogen and hydroxy; and 
 Y is hydrogen, —SO 2 NR 5 R 6 , —(CH 2 ) n NR 7 R 8 , —CH═N—OR 9 , —C(O)NR 7 R 8 , —C(O)R 9 , —CH(OH)R 9 , —(CH 2 ) n NHC(O)R 9 , —NHC(O)R 9 , —NHSO 2 R 9  and —(CH 2 ) n NHSO 2 R 9 ; 
 
         R 3  is hydrogen, C 1-4 alkyl, C 1-4 alkenyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, wherein said alkyl or alkenyl is optionally substituted with one or more hydroxy or chlorine; 
         R 4  is C 1-6 alkyl, C 1-6 alkenyl, C 3-8 cycloalkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1; or 
         R 3  and R 4  taken together with the carbon atoms to which they are attached form a C 4-8 cycloalkyl ring or a benzene ring; 
         R 5 , R 6 , R 7  and R 8  are the same or different and independently of each other selected from the group consisting of hydrogen, unsubstituted and at least monosubstituted C 1-10 alkyl, C 3-8  cycloalkyl, C 1-4  alkoxy-C 1-6 alkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, C 1-6 alkenyl, C 1-6 alkynyl, aryl, heteroaryl and heterocycle;
 wherein said substituents are selected from the group consisting of: aryl, heteroaryl, heterocycle, —O-aryl, fluorine, chlorine, bromine, —CF 3 , —OCF 3 , —NO 2 , —CN, —C(O)R 11 , —NHC(O)(C 1-3 alkyl), —NH 2 , hydroxy, C 1-6 alkyl, C 1-3  alkoxy, —NH(C 1-3  alkyl), —N(C 1-3  alkyl) 2 , —SO 2 NH 2 , —SO 2 (C 1-3  alkyl) and —NH—SO 2 (C 1 -C 3 -alkyl); and 
 aryl, heterocycle and heteroaryl may optionally be at least monosubstituted with fluorine, chlorine, bromine, oxo, —CF 3 , —OCF 3 , —NO 2 , —CN, heteroaryl, —NHC(O)(C 1-3 alkyl), —COOH, hydroxy, C 1-3 alkyl, C 1-3 alkoxy, —SO 2 NH 2 , —SO 2 NH(C 1-3 alkyl), —SO 2 N(C 1-3 alkyl) 2 , —C(O)NH 2 , —C(O)NH(C 1-3 alkyl), —C(O)N(C 1-3  alkyl) 2 , —SO 2 (C 1-3  alkyl), —NH 2 , —NH(C 1-3  alkyl) or —N(C 1-3 alkyl) 2 ; or 
 
         R 5  and R 6  taken together with the nitrogen atom to which they are attached form an unsubstituted or at least monosubstituted heterocycle; or 
         R 7  and R 8  taken together with the nitrogen atom to which they are attached form an unsubstituted or at least monosubstituted heterocycle;
 wherein said substituents are selected from: aryl, heteroaryl, heterocycle, oxo, fluorine, chlorine, bromine, —CF 3 , —OCF 3 , —NO 2 , —CN, —C(O)R 11 , —NHC(O)(C 1-3 alkyl), —NH 2 , hydroxy, C 1-3 alkyl, C 1-3 alkoxy, —NH(C 1-3 alkyl), —N(C 1-3 alkyl) 2 , —SO 2 NH 2 , —SO 2 (C 1-3 alkyl) and —NH—SO 2 (C 1-3 alkyl), and aryl, heterocycle and heteroaryl may optionally be at least monosubstituted with fluorine, chlorine, bromine, hydroxy, C 1-3 alkyl or C 1-3 alkoxy; 
 
         R 9  is hydrogen, unsubstituted or at least monosubstituted C 1-6 alkyl, phenyl, heteroaryl or heterocycle;
 wherein said substituents are selected from the group consisting of: fluorine, chlorine, bromine, aryl, heterocycle, heteroaryl, —CF 3 , —OCF 3 , —NO 2 , —CN, —C(O)R 11 , —NHC(O)(C 1-3 alkyl), —NH 2 , hydroxy, C 1-3 alkyl, C 1-3  alkoxy, —NH(C 1-3  alkyl), —N(C 1-3  alkyl) 2 , —SO 2 NH 2 , —SO 2  (C 1-3  alkyl) and —NH—SO 2  (C 1-3  alkyl); and 
 aryl, heterocycle and heteroaryl may optionally be at least monosubstituted with fluorine, chlorine, bromine, hydroxy, C 1-3 alkyl or C 1-3 alkoxy; 
 
         R 11  is hydroxy, C 1-3 alkoxy, —O-phenyl, —NH 2 , —NH(C 1-3 alkyl), —N(C 1-3  alkyl) 2  or phenyl; 
         n is an integer from 1 to 4; and wherein 
         heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclic heterocycle containing one or more heteroatoms selected from the group consisting of N, O and S; 
         aryl is a 6 to 10-membered, aromatic mono- or bicyclic ring; and 
         heterocycle is a 3 to 10-membered, non-aromatic, mono- or bicyclic heterocycle containing one or more heteroatoms selected from the group consisting of N, O and S; and 
         with the proviso that: 
         when Y and R are hydrogen, R 3  and R 4  are either hydrogen or methyl and R 1  is C 1-4  alkyl, then Ar is not 4(or 3)-hydroxyphenyl, 4(or 3)-methoxyphenyl, 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two C 1-4  alkyl substituents; 
         when Y is hydrogen, R is either hydrogen or methyl, R 1 ═R 3 ═R 4 =methyl, then Ar is not phenyl; and 
         when Y and R are hydrogen, R 3  and R 4  taken together with the carbon atoms to which they are attached form a benzene ring and R 1  is methyl, then Ar is not phenyl. 
       
     
     
         2 . The compound as set forth in  claim 1 , wherein R 2  is Ar—Y, wherein Ar is a substituted or unsubstituted aryl or aryloyl and Y is hydrogen. 
     
     
         3 . The compound as set forth in  claim 2 , wherein Ar is substituted or unsubstituted aryl. 
     
     
         4 . The compound as set forth in  claim 3 , wherein Ar is substituted phenyl. 
     
     
         5 . The compound as set forth in  claim 4 , wherein R is hydrogen, R 1  is hydrogen, methyl or ethyl, R 3  is hydrogen or methyl and R 4  is methyl, ethyl, propyl, isopropyl, isopropenyl or cyclopropyl. 
     
     
         6 . The compound as set forth in  claim 5 , which is selected from the group consisting of:
 3-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)benzonitrile;   3-(2,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)benzonitrile;   3-(5-ethyl-2,4-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)benzonitrile;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(morpholin-4-yl)methylbenzonitrile;   3-(5-n-propyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)benzonitrile;   3-(5-iso-propyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)benzonitrile;   3-(5-isopropenyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-benzonitrile;   3-(5-cyclopropyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-benzonitrile;   3-ethyl-6-methyl-5-phenyl-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(4-morpholin-4-ylmethyl-phenyl)-1H-pyridin-2-one hydrochloride;   3-(5-ethyl-6-oxo-1,6-dihydro-pyridin-3-yl)-benzonitrile; and   3-(2,5-diethyl-6-oxo-1,6-dihydro-pyridin-3-yl)-benzonitrile.   
     
     
         7 . The compound as set forth in  claim 4 , wherein R is hydrogen, R 1  is methyl, and R 3  and R 4  taken together form either cyclohexyl ring or benzene ring. 
     
     
         8 . The compound as set forth in  claim 7 , which is selected from the group consisting of:
 3-(3-methyl-1-oxo-1,2,5,6,7,8-hexahydroisoquinolin-4-yl)benzonitrile; and   3-(3-methyl-1-oxo-1,2-dihydroisoquinolin-4-yl)benzonitrile.   
     
     
         9 . The compound as set forth in  claim 2 , wherein Ar is substituted benzoyl. 
     
     
         10 . The compound as set forth in  claim 9 , wherein R is hydrogen, R 1  is methyl, R 3  is hydrogen and R 4  is ethyl. 
     
     
         11 . The compound as set forth in  claim 10 , which is 3-[(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridine)-3-carbonyl]benzonitrile. 
     
     
         12 . The compound as set forth in  claim 1 , wherein R 2  is Ar—Y, wherein Ar is substituted or unsubstituted heteroaryl and Y is hydrogen. 
     
     
         13 . The compound as set forth in  claim 12 , wherein the heteroaryl is selected from the group consisting of 1,2,3,-triazolyl, 1,3,4-triazolyl, 2H-1,2,4-triazolyl, 2-methyl-1,2,4-triazolyl, 2,5-dimethyl-1,2,4-triazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 5-methyl-1,3,4-oxadiazolyl, 3-methyl-1,2,4-oxadiazolyl, 5-methyl-1,2,4-oxadiazolyl, pyrazolyl, imidazolyl, pyrrolyl, furanyl, thiophenyl, and pyridinyl. 
     
     
         14 . The compound as set forth in  claim 13 , wherein R is hydrogen, R 1  is methyl, R 3  is hydrogen and R 4  is ethyl. 
     
     
         15 . The compound as set forth in  claim 14 , which is selected from the group consisting of:
 3-ethyl-6-methyl-5-(1,2,4-triazol-1-yl)-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-(1,2,3-triazol-2-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(1,2,3-triazol-1-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(2H-1,2,4-triazol-3-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(2-methyl-2H-1,2,4-triazol-3-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(5-methyl-2H-1,2,4-triazol-3-yl)-1H-pyridin-2-one;   5-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-3-ethyl-6-methyl-1H-pyridin-2-one;   3-ethyl-2-methoxy-6-methyl-5-(1,3,4-oxadiazol-2-yl)pyridine;   3-ethyl-6-methyl-5-(1,2,4-oxadiazol-5-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(1,2,4-oxadiazol-3-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(5-methyl-1,2,4-oxadiazol-3-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(3-methyl-1,2,4-oxadiazol-5-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(pyrazol-1-yl)-1H-pyridin-2-one hydrochloride;   3-ethyl-5-(imidazol-1-yl)-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-(pyrrol-1-yl)-1H-pyridin-2-one hydrochloride;   5-(5-aminomethyl-[1,3,4]oxadiazol-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one;   3-ethyl-6-methyl-5-[5-cyanofuran-2-yl]-1H-pyridin-2-one;   3-ethyl-6-methyl-5-[5-cyanothiophen-2-yl]-1H-pyridin-2-one;   3-ethyl-6-methyl-5-[5-nitrothiophen-2-yl]-1H-pyridin-2-one; and   5-ethyl-2-methyl-1H-[3,3′]bipyridinyl-6-one.   
     
     
         16 . The compound as set forth in  claim 1 , wherein Ar is substituted or unsubstituted thienyl, phenyl or pyridinyl. 
     
     
         17 . The compound as set forth in  claim 16 , wherein Ar is substituted or unsubstituted thienyl and Y is SO 2 NR 5 R 6  wherein
 R 5  and R 6  are the same or different and independently of each other selected from the group consisting of hydrogen, C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy-C 1-6 alkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, phenyl-C 0-4 alkyl, phenoxy-C 1-4 alkyl, phenyl-amino-C 1-4 alkyl, pyridinyl-C 0-4 alkyl, pyrazinyl-C 0-4 alkyl, furanyl-C 0-4 alkyl, tetrahydrofuranyl-C 0-4 alkyl, pyrrolidinyl-C 0-4 alkyl, morpholinyl-C 1-4 alkyl, imidazolyl-C 0-4 alkyl, indolyl-C 0-6 alkyl, benzimidazolyl-C 0-4 alkyl, piperidinyl-C 0-4 alkyl, piperazinyl-C 0-4 alkyl, pyrrolidinyl-C 0-4 alkyl, pyrazinyl-C 0-4 alkyl, dioxolanyl-C 0-4 alkyl and benzodioxolanyl-C 0-4 alkyl; or   R 5  and R 6  taken together with the nitrogen atom to which they are attached form a C 3-8 heterocycle ring optionally containing one or more heteroatoms selected from N, O or S;   and wherein where appropriate aforementioned groups are optionally substituted with one or more substituents selected from the group consisting of fluorine, chlorine, bromine, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, hydroxy-C 1-6 alkyl, hydroxy-C 1-6 alkoxy-C 1-6 alkyl, C 3-8 cycloalkyl-C 1-4 alkyl, trifluoromethyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, substituted or unsubstituted phenyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyrimidinyl-C 0-4 alkyl, substituted or unsubstituted pyrazinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidonyl-C 0-4 alkyl, substituted or unsubstituted piperidinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidinyl-C 0-4 alkyl, substituted or unsubstituted imidazolyl-C 0-4 alkyl, substituted or unsubstituted morpholinyl-C 0-4 alkyl, substituted or unsubstituted dioxolanyl-C 0-4 alkyl, substituted or unsubstituted bezodioxolanyl-C 0-4 alkyl, substituted or unsubstituted phenyl-amino-C 0-4 alkyl and substituted or unsubstituted benzoyl.   
     
     
         18 . The compound as set forth in  claim 17 , wherein R is hydrogen, R 1  is methyl, R 3  is hydrogen and R 4  is ethyl. 
     
     
         19 . The compound as set forth in  claim 18 , which is selected from the group consisting of:
 3-ethyl-6-methyl-5-[5-(4-phenylpiperazine-1-sulfonyl)thiophen-2-yl]-1H-pyridin-2-one;   3-ethyl-5-{5-[4-(4-fluorophenyl)piperazine-1-sulfonyl]thiophen-2-yl}-6-methyl-1H-pyridin-2-one;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid 4-trifluoromethylbenzylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid 3,5-difluorobenzylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid dimethylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (3,5-difluorobenzyl)methylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (pyridin-2-yl)methylamide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid 2-phenylaminoethylamide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-methoxyethyl)amide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (3-dimethylaminopropyl)amide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (5-methylfuran-2-yl)methylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-hydroxy-2-phenylethyl)methylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-morpholin-4-yl)ethylamide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (1-benzylpiperidin-4-yl)amide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-{1-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonyl]-1H-imidazol-4-yl}ethyl)amide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (1-tert-butyloxycarbonylpiperidin-4-yl)methylamide;   5-[5-ethyl-2-methyl-6-oxo-(1,6-dihydropyridin-3-yl)]thiophene-2-sulfonic acid (piperidin-4-yl)methylamide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid 1-(pyridin-2-yl)ethylamide hydrochloride;   3-ethyl-6-methyl-5-{5-[4-(2-piperidin-1-yl)ethylpiperizine-1-sulfonyl]thiophen-2-yl}-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-[5-(4-pyridin-4-yl)methylpiperizine-1-sulfonyl]thiophen-2-yl}-1H-pyridin-2-one dihydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophene-2-sulfonic acid (3-imidazol-1-yl)propylamide hydrochloride;   3-ethyl-6-methyl-5-{5-[4-(2-pyridin-2-yl)ethylpiperazine-1-sulfonyl]thiophen-2-yl}-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-{5-[4-(2-pyrrolidin-1-yl)ethylpiperazine-1-sulfonyl]thiophen-2-yl}-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-{5-[4-(3-pyrrolidin-1-yl)propylpiperazine-1-sulfonyl]thiophen-2-yl}-1H-pyridin-2-one dihydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-sulfonic acid (3-piperidin-1-yl-propyl)-amide hydrochloride;   5-{5-[4-(2-dimethylaminoethyl)piperazine-1-sulfonyl]thiophen-2-yl}-3-ethyl-6-methyl-1H-pyridin-2-one dihydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid 3-(4-methylpiperazin-1-yl)propylamide dihydrochloride;   3-ethyl-6-methyl-5-{5-[(4-pyrrolidin-1-yl)piperidine-1-sulfonyl]thiophen-2-yl}-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-{5-[(4-piperidin-1-yl)piperidine-1-sulfonyl]thiophen-2-yl}-1H-pyridin-2-one hydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophene-2-sulfonic acid (2-piperidin-1-yl)ethylamide hydrochloride;   3-ethyl-5-{5-[(3-imidazo-1-yl)methylpiperidine-1-sulfonyl]thiophene-2-yl}-6-methyl-1H-pyridin-2-one hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-dimethylamino-2-pyridin-3-yl)ethylamide dihydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophene-2-sulfonic acid 2-(morpholin-4-yl)-2-(pyridin-3-yl)ethylamide dihydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophene-2-sulfonic acid (6-methylpyrazin-2-yl)methylamide hydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophene-2-sulfonic acid (1-cyclopropylmethylpiperidin-4-yl)amide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (1-cyclohexylmethylpiperidin-4-yl)amide hydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]-thiophene-2-sulfonic acid [1-(4-chlorobenzyl)piperidin-4-yl]amide hydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophene-2-sulfonic acid methyl-(1-methylpiperidin-4-yl]amide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid [(6-dimethylaminopyridin-3-yl)methyl]amide hydrochloride;   3-ethyl-5-[5-(4-imidazol-1-yl)piperidine-1-sulfonyl)thiophen-2-yl]-6-methyl-1H-pyridin-2-one hydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophene-2-sulfonic acid (1-methylimidazol-2-yl)methyl]amide hydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophene-2-sulfonic acid [1-(pyridin-4-yl)methyl(piperidin-4-yl)]amide dihydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophene-2-sulfonic acid (1-imidazol-2-yl)methyl(piperidin-4-yl)]amide dihydrochloride;   5-[5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophene-2-sulfonic acid 4-(pyridin-3-ylbutyl)]amide hydrochloride;   3-ethyl-6-methyl-5-[5-(4-methylpiperazine-1-sulfonyl)thiophen-2-yl]-1H-pyridin-2-one;   3-ethyl-6-methyl-5-[5-(morpholine-4-sulfonyl)thiophen-2-yl]-1H-pyridin-2-one;   3-ethyl-5-[5-(4-hydroxypiperidine-1-sulfonyl)thiophen-2-yl]-6-methyl-1H-pyridin-2-one;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid [2-(1,3-dioxolan-2-yl)ethyl]amide;   4-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonyl]piperazine-1-carboxylic acid ethyl ester;   3-ethyl-5-[5-(3-hydroxymethylpiperidine-1-sulfonyl)thiophen-2-yl]-6-methyl-1H-pyridin-2-one;   3-ethyl-5-{5-[4-(2-hydroxyethyl)piperazine-1-sulfonyl]thiophen-2-yl}-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-[5-(4-methylpiperazine-1-sulfonyl)thiophen-2-yl]-1H-pyridin-2-one;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-dimethylaminoethyl)amide hydrochloride;   3-ethyl-6-methyl-5-[5-(piperazine-1-sulfonyl)thiophen-2-yl]-1H-pyridin-2-one hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)-thiophene-2-sulfonic acid (3-diethylaminopropyl)amide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)-thiophene-2-sulfonic acid (furan-2-ylmethyl)amide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)-thiophene-2-sulfonic acid (2-phenoxyethyl)amide;   3-ethyl-5-(5-{4-[2-(2-hydroxy-ethoxy)-ethyl]-piperazine-1-sulfonyl}-thiophen-2-yl)-6-methyl-1H-pyridin-2-one hydrochloride;   5-[5-(4-benzylpiperazine-1-sulfonyl)thiophen-2-yl]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)-thiophene-2-sulfonic acid (pyridin-3-ylmethyl)amide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)-thiophene-2-sulfonic acid (1,3-benzodioxol-5-ylmethyl)amide;   5-[5-(4-1,3-benzodioxol-5-ylmethylpiperazine-1-sulfonyl)-thiophen-2-yl]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)thiophene-2-sulfonic acid furan-2-yl-methyl-methylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-pyridin-3-yl-ethyl)amide hydrochloride;   5-[5-(4-benzylpiperidine-1-sulfonyl)thiophen-2-yl]-3-ethyl-6-methyl-1H-pyridin-2-one;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-pyridin-4-yl-ethyl)amide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (pyridin-4-ylmethyl)amide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid amide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (tetrahydrofuran-2-ylmethyl)amide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-hydroxypropyl)amide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-hydroxy-2-phenylethyl)amide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (2-hydroxyethyl)amide;   3-ethyl-6-methyl-5-{5-[(4-pyridin-2-yl)piperazine-1-sulfonyl]thiophen-2-yl}-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-[5-(4-pyrimidin-2-yl-piperazine-1-sulfonyl)thiophen-2-yl]-1H-pyridin-2-one hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)thiophene-2-sulfonic acid (1H-benzimidazol-2-ylmethyl)amide hydrochloride;   N-{2-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonylamino]ethyl}acetamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-sulfonic acid (3,5-difluoro-phenyl)-amide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid (1-methyl-1-pyridin-2-yl)ethylamide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid cyclopropyl (1-pyridin-2-yl)ethylamide dihydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-sulfonic acid (2-pyridin-2-yl-ethyl)-amide;   3-ethyl-6-methyl-5-[5-(4-methyl-[1,4]diazepane-1-sulfonyl)-thiophen-2-yl]-1H-pyridin-2-one;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-sulfonic acid benzylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-sulfonic acid 4-methoxy-benzylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-sulfonic acid 4-methanesulfonyl-benzylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-sulfonic acid (1H-indol-3-ylmethyl)-amide; or   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-sulfonic acid {3-[(1-ethyl-pyrrolidin-2-ylmethyl)-amino]-propyl}-amide.   
     
     
         20 . The compound as set forth in  claim 1 , wherein Ar is substituted or unsubstituted furanyl. 
     
     
         21 . The compound as set forth in  claim 20 , wherein Y is SO 2 NR 5 R 6  and wherein
 R 5  and R 6  are the same or different and independently of each other selected from the group consisting of hydrogen, C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy-C 1-6 alkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, phenyl-C 0-4 alkyl, phenoxy-C 1-4 alkyl, phenyl-amino-C 1-4 alkyl, pyridinyl-C 0-4 alkyl, pyrazinyl-C 0-4 alkyl, furanyl-C 0-4 alkyl, tetrahydrofuranyl-C 0-4 alkyl, pyrrolidinyl-C 0-4 alkyl, morpholinyl-C 1-4 alkyl, imidazolyl-C 0-4 alkyl, indolyl-C 0-6 alkyl, benzimidazolyl-C 0-4 alkyl, piperidinyl-C 0-4 alkyl, piperazinyl-C 0-4 alkyl, pyrrolidinyl-C 0-4 alkyl, pyrazinyl-C 0-4 alkyl, dioxolanyl-C 0-4 alkyl and benzodioxolanyl-C 0-4 alkyl; or   R 5  and R 6  taken together with the nitrogen atom to which they are attached form a C 3-8 heterocycle ring optionally containing one or more heteroatoms selected from N, O or S;   and wherein where appropriate aforementioned groups are optionally substituted with one or more substituents selected from the group consisting of fluorine, chlorine, bromine, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, hydroxy-C 1-6 alkyl, hydroxy-C 1-6 alkoxy-C 1-6 alkyl, C 3-8 cycloalkyl-C 1-4 alkyl, trifluoromethyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, substituted or unsubstituted phenyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyrimidinyl-C 0-4 alkyl, substituted or unsubstituted pyrazinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidonyl-C 0-4 alkyl, substituted or unsubstituted piperidinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidinyl-C 0-4 alkyl, substituted or unsubstituted imidazolyl-C 0-4 alkyl, substituted or unsubstituted morpholinyl-C 0-4 alkyl, substituted or unsubstituted dioxolanyl-C 0-4 alkyl, substituted or unsubstituted bezodioxolanyl-C 0-4 alkyl, substituted or unsubstituted phenyl-amino-C 0-4 alkyl and substituted or unsubstituted benzoyl.   
     
     
         22 . The compound as set forth in  claim 21 , wherein R is hydrogen, R 1  is methyl, R 3  is hydrogen and R 4  is ethyl. 
     
     
         23 . The compound as set forth in  claim 22 , which is selected from the group consisting of:
 5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-sulfonic acid (pyridin-2-yl)methylamide hydrochloride;   3-ethyl-6-methyl-5-{5-[(4-pyridin-4-yl)piperazine-1-sulfonyl]furan-2-yl}-1H-pyridin-2-one hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-sulfonic acid (1-benzylpiperidin-4-yl)amide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-sulfonic acid (2-morpholin-4-yl)ethylamide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-sulfonic acid (2-pyridin-3-yl)ethylamide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-sulfonic Acid (3-pyrrolidin-1-yl)propylamide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-sulfonic acid (2-piperidin-1-yl)ethylamide hydrochloride;   3-ethyl-6-methyl-5-[5-(4-piperidin-1-yl)piperidine-1-sulfonylfuran-2-yl]-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-[5-(4-methyl-1,4-diazepane-1-sulfonyl)furan-2-yl]-1H-pyridin-2-one hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-sulfonic acid (2-pyrrolidin-1-yl)ethylamide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-sulfonic acid (3-imidazol-1-yl)propylamide hydrochloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-sulfonic acid (pyridin-3-yl)methylamide hydrochloride; and   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-sulfonic acid 3,5-difluoro-benzylamide.   
     
     
         24 . The compound as set forth in  claim 16 , wherein Y is —(CH 2 ) n NR 7 R 8 , and wherein
 n is an integer from 1 to 4; 
 R 7  and R 8  are the same or different and independently of each other selected from the group consisting of hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl-C 0-4 alkyl, C 3-8 cycloalkenyl-C 0-4 alkyl, hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkylcarbonyl, phenyl-C 0-4 alkyl, phenoxy-C 1-4 alkyl, phenyl-amino-C 1-4 alkyl, pyridinyl-C 0-4 alkyl, pyrazinyl-C 0-4 alkyl, furanyl-C 0-4 alkyl, tetrahydrofuranyl-C 0-4 alkyl, thiophenyl-C 0-4 alkyl, pyrrolyl-C 0-4 alkyl, pyrrolidinyl-C 0-4 alkyl, morpholinyl-C 1-4 alkyl, imidazolyl-C 0-4 alkyl, pyrazolyl-C 0-4 alkyl, benzimidazolyl-C 0-4 alkyl, piperidinyl-C 0-4 alkyl, piperidinyl-C 1-4 alkylcarbonyl, piperazinyl-C 0-4 alkyl, tetrahydronaphthalenyl-C 0-4 alkyl, indanyl-C 0-4 alkyl, dioxolanyl-C 0-4 alkyl and benzodioxolanyl-C 0-4 alkyl; or 
 R 7  and R 8  taken together with the nitrogen atom to which they are attached form a C 3-8 heterocycle ring optionally containing one or more heteroatoms selected from N, O or S; 
 and wherein where appropriate aforementioned groups are optionally substituted with one or more substituents selected from the group consisting of fluorine, chlorine, bromine, oxo, hydroxy, —CF 3 , —OCF 3 , C 1-6 alkoxy, C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 3-8 cycloalkyl-C 1-4 alkyl, C 2-4 alkanoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, —SO 2 NH 2 , amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, substituted or unsubstituted phenyl-C 0-4  alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyrimidinyl-C 0-4 alkyl, substituted or unsubstituted pyrazinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidonyl-C 0-4 alkyl, substituted or unsubstituted piperidinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidinyl-C 0-4 alkyl, substituted or unsubstituted imidazolyl-C 0-4 alkyl, substituted or unsubstituted morpholinyl-C 0-4 alkyl, substituted or unsubstituted dioxolanyl-C 0-4 alkyl, substituted or unsubstituted bezodioxolanyl-C 0-4 alkyl, substituted or unsubstituted phenyl-amino-C 0-4 alkyl and substituted or unsubstituted benzoyl. 
 
     
     
         25 . The compound as set forth in  claim 24 , wherein R is hydrogen, R 1  is methyl, R 3  is hydrogen and R 4  is ethyl. 
     
     
         26 . The compound as set forth in  claim 25 , which is selected from the group consisting of:
 5-(5-aminomethylthiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-{5-[(4-hydroxycyclohexylamino)methyl]thiophen-2-yl]-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-[5-(3-hydroxypiperidin-1-ylmethyl)thiophen-2-yl]-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-[5-(4-hydroxy-piperidin-1-ylmethyl)-thiophen-2-yl]-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-{5-[(2-hydroxy-ethylamino)-methyl]thiophen-2-yl}-6-methyl-1H-pyridin-2-one hydrochloride;   5-(5-[1,4′]bipiperidinyl-1′-ylmethyl-thiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one dihydrochloride;   4-{[5-(5-ethyl-2-6-oxo-1,6-dyhydro-pyridin-3-yl)-thiophen-2-ylmethyl]-amino}-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester dihydrochloride;   3-ethyl-5-[5-(3-hydroxymethyl-piperidin-1-ylmethyl)-thiophen-2-yl]-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(1-cyclohexylmethyl-piperidin-4-ylamino)-methyl]thiophen-2-yl}-3-ethyl-6-methyl-1H-pyridin-2-one dihydrochloride;   5-{5-[(1-methylpyrrolidin-3-ylamino)-methyl]thiophen-2-yl}-3-ethyl-6-methyl-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-{5-[(1,2,3,4-tetrahydro-naphthalen-2-ylamino)-methyl]-thiophen-2-yl}-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-{5-[(1-phenyl-ethylamino)-methyl]thiophen-2-yl}-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-{5-[(1-methyl-3-phenyl-propylamino)-methyl]thiophen-2-yl}-1H-pyridin-2-one hydrochloride;   5-(5-cyclobutylaminomethyl-thiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-{5-[(2-methoxyethylamino)-methyl]thiophen-2-yl}-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-{5-[1-(4-trifluoromethylpyrimidin-2-yl)piperidin-4-ylamino]-thiophen-2-yl}-1H-pyridin-2-one dihydrochloride;   5-(5-{[1-(3,5-difluoro-benzyl)-)-piperidin-4-ylmethyl]-amino}methyl-thiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one;   3-ethyl-6-methyl-5-{5-[(2-pyridin-2-ylethylamino)methyl]thiophen-2-yl}-1H-pyridin-2-one dihydrochloride;   5-(5-cyclopropylaminomethyl-thiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-(5-cyclohexylmethylaminomethylthiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(2-cyclohex-1-enyl-ethylamino)-methyl]thiophen-2-yl}-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(3,5-difluoro-phenylamino)-methyl]thiophen-2-yl}-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-{5-[(2-phenoxyethylamino)-methyl]thiophen-2-yl}-1H-pyridin-2-one hydrochloride;   5-{5-[(3-methylbut-2-ylamino)methyl]thiophen-2-yl}-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-(5-piperidin-1-ylmethyl-thiophen-2-yl)-1H-pyridin-2-one hydrochloride;   5-[5-(1,4-dioxa-8-aza-spiro[4,5]dec-8-ylmethy)-thiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-[5-(4-oxo-piperidin-1-ylmethy)-thiophen-2-yl]-1H-pyridin-2-one hydrochloride;   5-{5-[(1-benzyl-piperidin-4-ylamino)-methyl]thiophen-2-yl}-3-ethyl-6-methyl-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-{5-{[(pyridin-4-ylmethyl)-amino]-methyl}-thiophen-2-yl)-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-{5-[(3-imidazol-1-yl-propylamino)-methyl]thiophen-2-yl)-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-{5-{[(2-pyrrolidin-1-ylethylamino)-methyl]thiophen-2-yl)-1H-pyridin-2-one dihydrochloride;   3-ethyl-5-(5-{[(2-(3H-imidazol-4-yl)ethylamino]methyl}thiophen-2-yl)-6-methyl-1H-pyridin-2-one dihydrochloride;   3-ethyl-5-[5-(indan-2-ylaminomethyl)-thiophen-2-yl]-6-methyl-1H-pyridin-2-one hydrochloride;   5-[5-(benzylamino-methyl)-thiophen-2-yl]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-[5-(3,5-difluorobenzylaminomethyl)thiophen-2-yl]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(1-benzyl-pyrrolidin-3-ylamino)-methyl]-thiophen-2-yl}-3-ethyl-6-methyl-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-[5-(4-pyrrolidin-1-ylpiperidin-1-ylmethyl)-thiophen-2-yl]-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-(5-{[(1-methyl-1H-imidazol-2-yl)methyl)amino]methyl}-thiophen-2-yl)-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-{5-{[(pyridin-3-ylmethyl)amino]methyl} thiophen-2-yl)-1H-pyridin-2-one dihydrochloride;   3-ethyl-6-methyl-5-{5-{[(pyridin-3-ylethyl)amino]methyl}thiophen-2-yl)-1H-pyridin-2-one dihydrochloride;   5-{5-[(3-chlorobenzylamino)methyl]thiophen-2-}]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(4-chlorobenzylamino)methyl]thiophen-2}]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(3-methylbenzylamino)methyl]thiophen-2-y}]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(4-methylbenzylamino)methyl]thiophen-2-y}]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(3-methoxybenzylamino)methyl]thiophen-2-y}]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(4-methoxybenzylamino)methyl]thiophen-2-y}]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-(5-{[(thiophen-2-ylmethyl)amino]methyl}-thiophen-2-yl)-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-(5-pyrrolidin-1-ylmethylthiophen-2-yl)-1H-pyridin-2-one hydrochloride;   5-{5-[(3,3-difluoropyrrolidin-1-ylmethyl)(thiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(3-fluoropyrrolidin-1-ylmethyl)(thiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-{5-[(3-methoxypyrrolidin-1-ylmethyl)(thiophen-2-yl)-6-methyl-1H-pyridin-2-one hydrochloride;   N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophen-2-ylmethyl]-2-(pyrrolidin-1-yl)acetamide hydrochloride;   2-dimethylamino-N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophen-2-ylmethyl]acetamide hydrochloride;   3-ethyl-5-{5-[(2-fluoro-3-trifluoromethylbenzylamino)methyl](thiophen-2-yl)-6-methyl-1H-pyridin-2-one hydrochloride;   5-[5-(4-benzylpiperidin-1-ylmethyl)thiophen-2-yl]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-[5-(4-phenylpiperidin-1-ylmethyl)thiophen-2-yl]-1H-pyridin-2-one hydrochloride;   3-ethyl-5-[5-(4-hydroxy-4-phenylpiperidin-1-ylmethyl)thiophen-2-yl]-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-(5-piperidin-1-yl)methylthiophen-2-yl]-1H-pyridin-2-one hydrochloride;   3-ethyl-5-{5-[(2-methoxybenzylamino)methyl]thiophen-2-yl}-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(2-chlorobenzylamino)methyl]thiophen-2-yl}-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-(5-cyclopentylaminomethylthiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   5-(5-cyclohexylaminomethylthiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-{5-[(S)-2-methoxymethylpyrrolidin-1-ylmethyl]thiophen-2-yl}-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-{5-[(2-fluoro-benzylamino)-methyl]-thiophen-2-yl}-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-[5-(3-fluoropiperidin-1-ylmethyl)thiophen-2-yl]-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-[5-(3-methoxypiperidin-1-ylmethyl)thiophen-2-yl]-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-(5-{[(pyridin-2-ylmethyl)amino]methyl}thiophen-2-yl)-1H-pyridin-2-one hydrochloride;   5-[5-(2-benzylaminoethyl)(thiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-6-methyl-5-[5-(2-pyrrolidin-1-ylethyl)thiophen-2-yl]-1H-pyridin-2-one hydrochloride;   5-(5-{[1-(3,5-difluoro-benzyl)-piperidin-4-ylamino]-methyl}-thiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(3-morpholin-4-ylmethyl-phenyl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(3-pyrrolidin-1-ylmethyl-phenyl)-1H-pyridin-2-one;   5-[3-(benzylamino-methyl)-phenyl]-3-ethyl-6-methyl-1H-pyridin-2-one;   5′-ethyl-2′-methyl-6-pyrrolidin-1-ylmethyl-1′H-[2,3′]bipyridinyl-6′-one;   5′-ethyl-2′-methyl-6-{[(pyridin-2-ylmethyl)-amino]-methyl}-1′H-[2,3′]bipyridinyl-6′-one;   5′-ethyl-6-(4-hydroxy-piperidin-1-ylmethyl)-2′-methyl-1′H-[2,3′]bipyridinyl-6′-one;   6-(4-acetyl-piperazin-1-ylmethyl)-5′-ethyl-2′-methyl-1′H-[2,3′]bipyridinyl-6′-one; and   5′-ethyl-2′-methyl-6-(4-pyrrolidin-1-yl-piperidin-1-ylmethyl)-1′H-[2,3′]bipyridinyl-6′-one.   
     
     
         27 . The compound as set forth in  claim 20 , wherein Y is —(CH 2 ) n NR 7 R 8 , wherein
 n is an integer from 1 to 4; 
 R 7  and R 8  are the same or different and independently of each other selected from the group consisting of hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl-C 0-4 alkyl, C 3-8 cycloalkenyl-C 0-4 alkyl, hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkylcarbonyl, phenyl-C 0-4 alkyl, phenoxy-C 1-4 alkyl, phenyl-amino-C 1-4 alkyl, pyridinyl-C 0-4 alkyl, pyrazinyl-C 0-4 alkyl, furanyl-C 0-4 alkyl, tetrahydrofuranyl-C 0-4 alkyl, thiophenyl-C 0-4 alkyl, pyrrolyl-C 0-4 alkyl, pyrrolidinyl-C 0-4 alkyl, morpholinyl-C 1-4 alkyl, imidazolyl-C 0-4 alkyl, pyrazolyl-C 0-4 alkyl, benzimidazolyl-C 0-4 alkyl, piperidinyl-C 0-4 alkyl, piperidinyl-C 1-4 alkylcarbonyl, piperazinyl-C 0-4 alkyl, tetrahydronaphthalenyl-C 0-4 alkyl, indanyl-C 0-4 alkyl, dioxolanyl-C 0-4 alkyl and benzodioxolanyl-C 0-4 alkyl; or 
 R 7  and R 8  taken together with the nitrogen atom to which they are attached form a C 3-8 heterocycle ring optionally containing one or more heteroatoms selected from N, O or S; 
 and wherein where appropriate aforementioned groups are optionally substituted with one or more substituents selected from the group consisting of fluorine, chlorine, bromine, oxo, hydroxy, —CF 3 , —OCF 3 , C 1-6 alkoxy, C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 3-8 cycloalkyl-C 1-4 alkyl, C 2-4 alkanoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, —SO 2 NH 2 , amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, substituted or unsubstituted phenyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyrimidinyl-C 0-4 alkyl, substituted or unsubstituted pyrazinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidonyl-C 0-4 alkyl, substituted or unsubstituted piperidinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidinyl-C 0-4 alkyl, substituted or unsubstituted imidazolyl-C 0-4 alkyl, substituted or unsubstituted morpholinyl-C 0-4 alkyl, substituted or unsubstituted dioxolanyl-C 0-4 alkyl, substituted or unsubstituted bezodioxolanyl-C 0-4 alkyl, substituted or unsubstituted phenyl-amino-C 0-4 alkyl and substituted or unsubstituted benzoyl. 
 
     
     
         28 . The compound as set forth in  claim 27 , wherein R is hydrogen, R 1  is methyl, R 3  is hydrogen and R 4  is ethyl. 
     
     
         29 . The compound as set forth in  claim 28 , which is selected from the group consisting of:
 5-[5-(benzylamino-methyl)-furan-2-yl]-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride;   3-ethyl-5-[5-(3-hydroxypyrrolidin-1-ylmethyl)furan-2-yl]-6-methyl-1H-pyridin-2-one hydrochloride;   5-{5-[(benzyl methylamino)methyl]furan-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one;   3-ethyl-6-methyl-5-{5-[(morpholin-4-ylmethylfuran-2-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-{5-[(pyrrolidin-1-ylmethylfuran-2-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-{5-[(3-fluoropyrrolidin-1-ylmethylfuran-2-yl)-1H-pyridin-2-one hydrochloride;   5-(5-aminomethyl-furan-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one;   5-{5-[(benzyl-pyridin-3-ylmethyl-amino)-methyl]-furan-2-yl}-3-ethyl-6-methyl-1H-pyridin-2-one;   N-[4-({[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-ylmethyl]-amino}-methyl)-phenyl]-acetamide;   2-chloro-5-(2-{[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-ylmethyl]-amino}-ethyl)-benzenesulfonamide;   3-ethyl-6-methyl-5-(5-{[(1-methyl-1H-pyrazol-4-ylmethyl)-amino]-methyl}-furan-2-yl)-1H-pyridin-2-one;   3-ethyl-6-methyl-5-{5-[(2-trifluoromethoxy-benzylamino)-methyl]-furan-2-yl}-1H-pyridin-2-one;   3-ethyl-6-methyl-5-(5-pyrrolidin-1-ylmethyl-furan-3-yl)-1H-pyridin-2-one; and   3-ethyl-6-methyl-5-(5-pyrrolidin-1-ylmethyl-furan-3-yl)-1H-pyridin-2-one.   
     
     
         30 . The compound as set forth in  claim 1 , wherein Ar is substituted or unsubstituted phenyl, thienyl, furanyl, pyridinyl, and Y is hydrogen, —CH═N—OR 9 , —C(O)NR 7 R 8 , —C(O)R 9 , —CH(OH)R 9 , —(CH 2 ) n NHC(O)R 9 , or —NHSO 2 R 9 ; and wherein
 n is an integer from 1 to 4; 
 R 7  and R 8  are the same or different and independently of each other selected from the group consisting of hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl-C 0-4 alkyl, C 3-8  cycloalkenyl-C 0-4 alkyl, hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, amino-C 1-6 alkyl, aminocarbonylC 1-4 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkylcarbonyl, phenyl-C 0-4 alkyl, phenoxy-C 1-4 alkyl, phenyl-amino-C 1-4 alkyl, pyridinyl-C 0-4 alkyl, pyrazinyl-C 0-4 alkyl, furanyl-C 0-4 alkyl, tetrahydrofuranyl-C 0-4 alkyl, thiophenyl-C 0-4 alkyl, pyrrolyl-C 0-4 alkyl, pyrrolidinyl-C 0-4 alkyl, morpholinyl-C 1-4 alkyl, imidazolyl-C 0-4 alkyl, pyrazolyl-C 0-4 alkyl, triazolyl-C 0-4 alkyl, thiazolyl-C 0-4 alkyl, dioxo-thiazolidinyl-C 0-4 alkyl, dihydro-isoxazolyl-C 0-4 alkyl, isoxazolyl-C 0-4 alkyl, indolyl-C 0-4 alkyl, benzimidazolyl-C 0-4 alkyl, piperidinyl-C 0-4 alkyl, piperidinyl-C 1-4 alkylcarbonyl, piperazinyl-C 0-4 alkyl, tetrahydronaphthalenyl-C 0-4 alkyl, indanyl-C 0-4 alkyl, dioxolanyl-C 0-4 alkyl and benzodioxolanyl-C 0-4 alkyl; or 
 R 7  and R 8  taken together with the nitrogen atom to which they are attached form a C 3-8 heterocycle ring optionally containing one or more heteroatoms selected from N, O or S; 
 R 9  is hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, phenyl-C 0-4 alkyl, phenyl-amino-C 1-4 alkyl, pyridinyl-C 1-4 alkyl, pyrrolyl-C 1-4 alkyl, pyrrolidinyl-C 1-4 alkyl, morpholinyl-C 1-4 alkyl, imidazolyl-C 1-4 alkyl, benzimidazolyl-C 1-4 alkyl, piperidinyl-C 1-4 alkyl, piperazinyl-C 1-4 alkyl, pyrazinyl-C 1-4 alkyl; 
 and wherein where appropriate aforementioned groups are optionally substituted with one or more substituents selected from the group consisting of fluorine, chlorine, bromine, oxo, hydroxy, —CF 3 , —OCF 3 , C 1-6 alkoxy, C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 3-8 cycloalkyl-C 1-4 alkyl, C 2-4 alkanoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, —SO 2 NH 2 , amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, substituted or unsubstituted phenyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyrimidinyl-C 0-4 alkyl, substituted or unsubstituted pyrazinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidonyl-C 0-4 alkyl, substituted or unsubstituted piperidinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidinyl-C 0-4 alkyl, substituted or unsubstituted imidazolyl-C 0-4 alkyl, substituted or unsubstituted morpholinyl-C 0-4 alkyl, substituted or unsubstituted dioxolanyl-C 0-4 alkyl, substituted or unsubstituted bezodioxolanyl-C 0-4 alkyl, substituted or unsubstituted phenyl-amino-C 0-4 alkyl and substituted or unsubstituted benzoyl. 
 
     
     
         31 . The compound as set forth in  claim 30 , wherein R is hydrogen, R 1  is methyl, R 3  is hydrogen and R 4  is ethyl. 
     
     
         32 . The compound as set forth in  claim 31 , which is selected from the group consisting of:
 3-ethyl-6-methyl-5-thiophen-2-yl-1H-pyridin-2-one;   3-ethyl-6-methyl-5-furan-2-yl-1H-pyridin-2-one;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]thiophen-2-methanol;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl]furan-2-methanol;   3-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)-benzaldehyde;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-carbaldehyde;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-carbaldehyde;   4-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-carbaldehyde;   5-[5-(ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophen-2-yl]acetaldehyde;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-carbaldehyde oxime;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-carbaldehyde-O-benzyl-oxime;   3-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl-thiophene-2-carbaldehyde-O-(pyrrolidin-1-ylethyl)oxime hydrochloride;   3-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl-furan-2-carbaldehyde-O-(pyrrolidin-1-ylethyl)oxime hydrochloride;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-4-carboxylic acid;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-5-carboxylic acid;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-6-carboxylic acid;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-6-carbaldehyde;   6-amino-5′-ethyl-2′-methyl-1′H-[2,3′]bipyridinyl-6′-one;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)-thiophene-2-sulfonyl chloride;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)-furan-2-sulfonyl chloride;   3-ethyl-6-methyl-5-[5-(4-phenyl-piperazine-1-carbonyl)-furan-2-yl]-1H-pyridin-2-one;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-carboxylic acid cyclopropylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-carboxylic acid 3,5-difluoro-benzylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-carboxylic acid (pyridin-2-ylmethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-6-carboxylic acid [2-(4-nitro-phenyl)-ethyl]-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-6-carboxylic acid butylamide;   5′-ethyl-2′-methyl-6-(pyrrolidine-1-carbonyl)-1′H-[2,3′]bipyridinyl-6′-one;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-5-carboxylic acid (pyridin-2-ylmethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-5-carboxylic acid butylamide;   5′-ethyl-5-(3-hydroxy-pyrrolidine-1-carbonyl)-2′-methyl-1′H-[2,3′]bipyridinyl-6′-one;   5′-ethyl-2′-methyl-5-(pyrrolidine-1-carbonyl)-1′H-[2,3′]bipyridinyl-6′-one;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-5-carboxylic acid cyclopentylamide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-4-carboxylic acid [2-(4-nitro-phenyl)-ethyl]-amide;   5′-ethyl-2′-methyl-4-(pyrrolidine-1-carbonyl)-1′H-[2,3′]bipyridinyl-6′-one;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-4-carboxylic acid butylamide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-4-carboxylic acid cyclopentylamide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-4-carboxylic acid (2-morpholin-4-yl-ethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-4-carboxylic acid (2-pyridin-4-yl-ethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid cyclopentylamide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid benzylamide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (pyridin-2-ylmethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (pyridin-3-ylmethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid butylamide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [1-(6-methyl-pyridin-3-yl)-propyl]-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid carbamoylmethyl-amide;   5-ethyl-2-methyl-5′-(pyrrolidine-1-carbonyl)-1H-[3,3′]bipyridinyl-6-one;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid diethylamide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (cyclopropyl-pyridin-3-yl-methyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (2-hydroxy-propyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [2-(4-nitro-phenyl)-ethyl]-amide;   1-(5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carbonyl)-4-hydroxy-pyrrolidine-2-carboxylic acid methyl ester;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [2-(2-hydroxy-phenyl)-ethyl]-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid carbamoylmethyl-methyl-amide;   5-ethyl-2-methyl-5′-(4-oxo-piperidine-1-carbonyl)-1H-[3,3′]bipyridinyl-6-one;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid ethyl-pyridin-4-ylmethyl-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid phenethyl-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [2-(4-sulfamoyl-phenyl)-ethyl]-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (2-pyridin-4-yl-ethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [2-(4-methoxy-phenyl)-ethyl]-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [2-(3-methoxy-phenyl)-ethyl]-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (2-morpholin-4-yl-ethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [2-(tetrahydro-pyran-4-yl)-ethyl]-amide;   4-{2-[(5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carbonyl)-amino]-ethyl}-benzoic acid;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (2-oxo-2-phenyl-ethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [2-(1H-benzoimidazol-2-yl)-ethyl]-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (4-acetyl-phenyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (3-[1,2,4]triazol-1-yl-propyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (3-methoxy-phenyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl]-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (thiazol-2-ylmethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (2-carbamoylmethyl-phenyl)-amide;   5′-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-5-ethyl-2-methyl-1H-[3,3′]bipyridinyl-6-one;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (2-hydroxy-2-phenyl-ethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [2-(2,4-dioxo-thiazolidin-3-yl)-ethyl]-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid 4-sulfamoyl-benzylamide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid [2-(4-methoxy-phenyl)-2-oxo-ethyl]-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (3-pyridin-4-yl-4,5-dihydro-isoxazol-5-ylmethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (5-tert-butyl-1H-pyrazol-3-yl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid ((1S,6R)-6-carbamoyl-cyclohex-3-enyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (2-methoxy-ethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (4-cyano-cyclohexylmethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid 3-methoxy-benzylamide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid (2-pyridin-2-yl-ethyl)-amide;   5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid 4-hydroxy-3-methoxy-benzylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-carboxylic acid 3,5-difluoro-benzylamide;   3-ethyl-6-methyl-5-[5-(2-methyl-aziridine-1-carbonyl)-furan-2-yl]-1H-pyridin-2-one;   3-ethyl-5-{5-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-furan-2-yl}-6-methyl-1H-pyridin-2-one;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-carboxylic acid 4-trifluoromethyl-benzylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-carboxylic acid dimethylamide;   5-[5-(4-benzyl-piperazine-1-carbonyl)-thiophen-2-yl]-3-ethyl-6-methyl-1H-pyridin-2-one;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-carboxylic acid dimethylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-carboxylic acid 4-trifluoromethyl-benzylamide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-carboxylic acid (pyridin-2-ylmethyl)-amide;   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophene-2-carboxylic acid methoxy-methyl-amide;   3-ethyl-6-methyl-5-[5-(pyridine-2-carbonyl)-thiophen-2-yl]-1H-pyridin-2-one;   3-ethyl-5-[5-(hydroxy-pyridin-2-yl-methyl)-thiophen-2-yl]-6-methyl-1H-pyridin-2-one;   3-ethyl-5-[5-(1-hydroxy-ethyl)-furan-2-yl]-6-methyl-1H-pyridin-2-one;   cyclopentanecarboxylic acid [5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-ylmethyl]-amide;   N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-ylmethyl]-2-phenyl-acetamide;   N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-ylmethyl]-benzamide;   N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-ylmethyl]-4-methoxy-benzamide;   pyridine-2-carboxylic acid [5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-ylmethyl]-amide;   N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-ylmethyl]-acetamide;   3-dimethylamino-N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-ylmethyl]-benzamide;   N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophen-2-ylmethyl]-2-pyrrolidin-1-yl-acetamide;   N-(5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-6-yl)-benzenesulfonamide;   N-[4-(5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-6-ylsulfamoyl)-phenyl]-acetamide; and   5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-furan-2-carboxylic acid amide.   
     
     
         33 . A compound, including enantiomers, stereoisomers, and tautomers of said compound and pharmaceutically acceptable salts, solvates or derivatives thereof, with said compound having the general structure shown in formula II: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is C 1-4 alkyl, C 1-4 alkenyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, wherein said alkyl or alkenyl is optionally substituted with one or more hydroxy or chlorine; 
         R 3  is hydrogen, C 1-4 alkyl, C 1-4 alkenyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, wherein said alkyl or alkenyl is optionally substituted with one or more hydroxy or chlorine; 
         R 4  is C 1-6 alkyl, C 1-6 alkenyl, C 3-8 cycloalkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1; or 
         R 3  and R 4  taken together with the carbon atoms to which they are attached form a C 4-8 cycloalkyl ring or a benzene ring; 
         R 10  is C 1-4 alkyl, phenyl-C 1-4 alkyl, C 1-4 alkenyl, fluoroalkyl of the formula C n H 8 F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1; and 
         X is fluorine, chlorine, bromine, substituted or unsubstituted phenyl, thienyl, furanyl or pyridinyl, wherein the substituents are selected from the group consisting of: —CHO, —CO 2 H, —CO 2 C 1-4 alkyl or —NH 2 . 
       
     
     
         34 . The compound as set forth in  claim 33 , wherein R 1 , R 4  and R 10  independently from each other are either methyl or ethyl and R 3  is hydrogen. 
     
     
         35 . The compound as set forth in  claim 34  selected from the group consisting of:
 3-bromo-5-ethyl-6-methoxy-2-methylpyridine; 
 3-(5-ethyl-6-methoxy-2-methyl-pyridin-3-y0-benzaldehyde; 
 3-ethyl-2-methoxy-6-methyl-5-thiophen-2-yl-pyridine; 
 3-ethyl-2-methoxy-6-methyl-5-furan-2-yl-pyridine; 
 5-(5-ethyl-6-methoxy-2-methyl-pyridin-3-yl)-thiophene-2-carbaldehyde; 
 5-(5-ethyl-6-methoxy-2-methyl-pyridin-3-yl)-furan-2-carbaldehyde; 
 4-(5-ethyl-6-methoxy-2-methyl-pyridin-3-yl)-furan-2-carbaldehyde; 
 5′-ethyl-6′-methoxy-2′-methyl-[2,3′]bipyridinyl-6-carbaldehyde; 
 5′-ethyl-6′-methoxy-2′-methyl-[3,3′]bipyridinyl-5-carboxylic acid; 
 5′-ethyl-6′-methoxy-2′-methyl-[2,3′]bipyridinyl-4-carboxylic acid; 
 5′-ethyl-6′-methoxy-2′-methyl-[2,3′]bipyridinyl-6-carboxylic acid; 
 5′-ethyl-6′-methoxy-2′-methyl-[2,3′]bipyridinyl-5-carboxylic acid; and 
 5′-ethyl-6′-methoxy-2′-methyl-[2,3′]bipyridinyl-6-ylamine. 
 
     
     
         36 . A method of treating a disease selected from the group consisting of stimulation of damaged neurons, promotion of neuronal regeneration, prevention of neurodegeneration, treatment of a neurological disorder, coronary artery disease, myocardial infarction, angina pectoris, cardiogenic shock and cardiovascular tissue damage in a patient comprising administering to said patient a therapeutically effective amount of a compound, including enantiomers, stereoisomers, and tautomers of said compound and pharmaceutically acceptable salts, solvates or derivatives thereof, with said compound having the general structure shown in formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R is hydrogen, C 1-6 alkyl; 
         R 1  is C 1-4 alkyl, C 1-4 alkenyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, wherein said alkyl or alkenyl is optionally substituted with one or more hydroxy or chlorine; 
         R 2  is Ar—Y, wherein
 Ar is substituted or unsubstituted aryl, aryloyl or heteroaryl wherein said substituents are selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkenyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, —NO 2 , —CH 2 NH 2 , —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —C(O)R 11 , —NHC(O)(C 1-4 alkyl), —SO 2 Cl, —SO 2 (C 1-4 alkyl), halogen and hydroxy; and 
 Y is hydrogen, —SO 2 NR 5 R 6 , —(CH 2 ) n NR 7 R 8 , —CH═N—OR 9 , —C(O)NR 7 R 8 , —C(O)R 9 , —CH(OH)R 9 , —(CH 2 ) n NHC(O)R 9 , —NHC(O)R 9 , —NHSO 2 R 9  and —(CH 2 ) n NHSO 2 R 9 ; 
 
         R 3  is hydrogen, C 1-4 alkyl, C 1-4 alkenyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, wherein said alkyl or alkenyl is optionally substituted with one or more hydroxy or chlorine; 
         R 4  is C 1-6 alkyl, C 1-6 alkenyl, C 3-8 cycloalkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1; or 
         R 3  and R 4  taken together with the carbon atoms to which they are attached form a C 4-8 cycloalkyl ring or a benzene ring; 
         R 5 , R 6 , R 7  and R 8  are the same or different and independently of each other selected from the group consisting of hydrogen, unsubstituted and at least monosubstituted C 1-10 alkyl, C 3-8  cycloalkyl, C 1-4 alkoxy-C 1-6 alkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, C 1-6 alkenyl, C 1-6 alkynyl, aryl, heteroaryl and heterocycle;
 wherein said substituents are selected from the group consisting of: aryl, heteroaryl, heterocycle, —O-aryl, fluorine, chlorine, bromine, —CF 3 , —OCF 3 , —NO 2 , —CN, —C(O)R 11 , —NHC(O)(C 1-3 alkyl), —NH 2 , hydroxy, C 1-6 alkyl, C 1-3  alkoxy, —NH(C 1-3  alkyl), —N(C 1-3 alkyl) 2 , —SO 2 NH 2 , —SO 2 (C 1-3  alkyl) and —NH—SO 2 (C 1 -C 3 -alkyl); and 
 aryl, heterocycle and heteroaryl may optionally be at least monosubstituted with fluorine, chlorine, bromine, oxo, —CF 3 , —OCF 3 , —NO 2 , —CN, heteroaryl, —NHC(O)(C 1-3 alkyl), —COOH, hydroxy, C 1-3 alkyl, C 1-3 alkoxy, —SO 2 NH 2 , —SO 2 NH(C 1-3 alkyl), —SO 2 N(C 1-3 alkyl) 2 , —C(O)NH 2 , —C(O)NH(C 1-3 alkyl), —C(O)N(C 1-3 alkyl) 2 , —SO 2 (C 1-3 alkyl), —NH 2 , —NH(C 1-3 alkyl) or —N(C 1-3 alkyl) 2 ; or 
 
         R 5  and R 6  taken together with the nitrogen atom to which they are attached form an unsubstituted or at least monosubstituted heterocycle; or 
         R 7  and R 8  taken together with the nitrogen atom to which they are attached form an unsubstituted or at least monosubstituted heterocycle;
 wherein said substituents are selected from: aryl, heteroaryl, heterocycle, oxo, fluorine, chlorine, bromine, —CF 3 , —OCF 3 , —NO 2 , —CN, —C(O)R 11 , —NHC(O)(C 1-3 alkyl), —NH 2 , hydroxy, C 1-3 alkyl, C 1-3 alkoxy, —NH(C 1-3 alkyl), —N(C 1-3 alkyl) 2 , —SO 2 NH 2 , —SO 2 (C 1-3 alkyl) and —NH—SO 2 (C 1-3 alkyl), and aryl, heterocycle and heteroaryl may optionally be at least monosubstituted with fluorine, chlorine, bromine, hydroxy, C 1-3 alkyl or C 1-3 alkoxy; 
 
         R 9  is hydrogen, unsubstituted or at least monosubstituted C 1-6 alkyl, phenyl, heteroaryl or heterocycle;
 wherein said substituents are selected from the group consisting of: fluorine, chlorine, bromine, aryl, heterocycle, heteroaryl, —CF 3 , —OCF 3 , —NO 2 , —CN, —C(O)R 11 , —NHC(O)(C 1-3 alkyl), —NH 2 , hydroxy, C 1-3 alkyl, C 1-3 alkoxy, —NH(C 1-3 alkyl), —N(C 1-3 alkyl) 2 , —SO 2 NH 2 , —SO 2 (C 1-3 alkyl) and —NH—SO 2  (C 1-3 alkyl); and 
 aryl, heterocycle and heteroaryl may optionally be at least monosubstituted with fluorine, chlorine, bromine, hydroxy, C 1-3 alkyl or C 1-3 alkoxy; 
 
         R 11  is hydroxy, C 1-3 alkoxy, —O-phenyl, —NH 2 , —NH(C 1-3 alkyl), —N(C 1-3 alkyl) 2  or phenyl; 
         n is an integer from 1 to 4; and wherein 
         heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclic heterocycle containing one or more heteroatoms selected from the group consisting of N, O and S; 
         aryl is a 6 to 10-membered, aromatic mono- or bicyclic ring; and 
         heterocycle is a 3 to 10-membered, non-aromatic, mono- or bicyclic heterocycle containing one or more heteroatoms selected from the group consisting of N, O and S; and 
         with the proviso that: 
         when Y and R are hydrogen, R 3  and R 4  are either hydrogen or methyl and R 1  is C 1-4 alkyl, then Ar is not 4(or 3)-hydroxyphenyl, 4(or 3)-methoxyphenyl, 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two C 1-4 alkyl substituents; 
         when Y is hydrogen, R is either hydrogen or methyl, R 1 ═R 3 ═R 4 =methyl, then Ar is not phenyl; and 
         when Y and R are hydrogen, R 3  and R 4  taken together with the carbon atoms to which they are attached form a benzene ring and R 1  is methyl, then Ar is not phenyl. 
       
     
     
         37 . The method as set forth in  claim 36 , wherein
 R is hydrogen, methyl or ethyl;   R 1  is methyl or ethyl;   R 3  is hydrogen, methyl or ethyl;   R 4  is methyl or ethyl; or   R 3  and R 4  taken together form either cyclohexyl ring or benzene ring;   Ar is substituted phenyl, substituted benzoyl, substituted or unsubstituted heteroaryl selected from the group consisting of 1,2,3,-triazolyl, 1,3,4-triazolyl, 2H-1,2,4-triazolyl, 2-methyl-1,2,4-triazolyl, 2,5-dimethyl-1,2,4-triazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 5-methyl-1,3,4-oxadiazolyl, 3-methyl-1,2,4-oxadiazolyl, 5-methyl-1,2,4-oxadiazolyl, pyrazolyl, imidazolyl, pyrrolyl, pyridinyl, thienyl or furanyl;   Y is hydrogen, —SO 2 NR 5 R 6 , —(CH 2 ) n NR 7 R 8 , —CH═N—OR 9 , —C(O)NR 7 R 8 , —C(O)R 9 , —CH(OH)R 9 , —(CH 2 ) n NHC(O)R 9 , and —NHSO 2 R 9 ;   R 5  and R 6  are the same or different and independently of each other selected from the group consisting of hydrogen, C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy-C 1-6 alkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, phenyl-C 0-4 alkyl, phenoxy-C 1-4 alkyl, phenyl-amino-C 1-4 alkyl, pyridinyl-C 0-4 alkyl, pyrazinyl-C 0-4 alkyl, furanyl-C 0-4 alkyl, tetrahydrofuranyl-C 0-4 alkyl, pyrrolidinyl-C 0-4 alkyl, morpholinyl-C 1-4 alkyl, imidazolyl-C 0-4 alkyl, indolyl-C 0-6 alkyl, benzimidazolyl-C 0-4 alkyl, piperidinyl-C 0-4 alkyl, piperazinyl-C 0-4 alkyl, pyrrolidinyl-C 0-4 alkyl, pyrazinyl-C 0-4 alkyl, dioxolanyl-C 0-4 alkyl and benzodioxolanyl-C 0-4 alkyl; or   R 5  and R 6  taken together with the nitrogen atom to which they are attached form a C 3-8 heterocycle ring optionally containing one or more heteroatoms selected from N, O or S;   n is an integer from 1 to 4;   R 7  and R 8  are the same or different and independently of each other selected from the group consisting of hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl-C 0-4 alkyl, C 3-8 cycloalkenyl-C 0-4 alkyl, hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl, fluoroalkyl or fluoroalkoxy of the formula C n H x F y  or OC n H x F y  wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkylcarbonyl, phenyl-C 0-4 alkyl, phenoxy-C 1-4 alkyl, phenyl-amino-C 1-4 alkyl, pyridinyl-C 0-4 alkyl, pyrazinyl-C 0-4 alkyl, furanyl-C 0-4 alkyl, tetrahydrofuranyl-C 0-4 alkyl, thiophenyl-C 0-4 alkyl, pyrrolyl-C 0-4 alkyl, pyrrolidinyl-C 0-4 alkyl, morpholinyl-C 1-4 alkyl, imidazolyl-C 0-4 alkyl, pyrazolyl-C 0-4 alkyl, benzimidazolyl-C 0-4 alkyl, piperidinyl-C 0-4 alkyl, piperidinyl-C 1-4 alkylcarbonyl, piperazinyl-C 0-4 alkyl, tetrahydronaphthalenyl-C 0-4 alkyl, indanyl-C 0-4 alkyl, dioxolanyl-C 0-4 alkyl and benzodioxolanyl-C 0-4 alkyl; or   R 7  and R 8  taken together with the nitrogen atom to which they are attached form a C 3-8 heterocycle ring optionally containing one or more heteroatoms selected from N, O or S;   and wherein where appropriate aforementioned groups are optionally substituted with one or more substituents selected from the group consisting of fluorine, chlorine, bromine, oxo, hydroxy, —CF 3 , —OCF 3 , C 1-6 alkoxy, C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 3-8 cycloalkyl-C 1-4 alkyl, C 2-4 alkanoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, —SO 2 NH 2 , amino-C 1-6 alkyl, C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 dialkyl-amino-C 1-6 alkyl, substituted or unsubstituted phenyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyridinyl-C 0-4 alkyl, substituted or unsubstituted pyrimidinyl-C 0-4 alkyl, substituted or unsubstituted pyrazinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidonyl-C 0-4 alkyl, substituted or unsubstituted piperidinyl-C 0-4 alkyl, substituted or unsubstituted pyrrolidinyl-C 0-4 alkyl, substituted or unsubstituted imidazolyl-C 0-4 alkyl, substituted or unsubstituted morpholinyl-C 0-4 alkyl, substituted or unsubstituted dioxolanyl-C 0-4 alkyl, substituted or unsubstituted bezodioxolanyl-C 0-4 alkyl, substituted or unsubstituted phenyl-amino-C 0-4 alkyl and substituted or unsubstituted benzoyl.   
     
     
         38 . A pharmaceutical composition comprising one or more compounds of  claim 1  in combination with one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         39 . A pharmaceutical composition comprising one or more compounds of  claim 5  in combination with one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         40 . A pharmaceutical composition comprising one or more compounds of  claim 7  in combination with one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         41 . A pharmaceutical composition comprising one or more compounds of  claim 10  in combination with one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         42 . A pharmaceutical composition comprising one or more compounds of  claim 14  in combination with one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         43 . A pharmaceutical composition comprising one or more compounds of  claim 18  in combination with one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         44 . A pharmaceutical composition comprising one or more compounds of  claim 22  in combination with one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         45 . A pharmaceutical composition comprising one or more compounds of  claim 25  in combination with one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         46 . A pharmaceutical composition comprising one or more compounds of  claim 28  in combination with one or more pharmaceutically acceptable carriers, diluents or excipients.