The invention relates to inhibitorsof apoptosis signal-regulating kinase 1 (“ASK1”), a process for synthesis of the compounds of the present invention, composition comprising the compounds and use of the compounds for inhibition of ASK1.

BACKGROUND OF THE INVENTION

Apoptosis signal-regulating kinase 1 (ASK1), is a member of the mitogen-activated protein kinases (MAPKs) family, which are members of the serine/threonine kinase family. ASK1 is also known as mitogen-activated protein kinase kinasekinase 5 (MAPKKK5, MAP3K5), MAP/ERK kinase kinase 5 (MEKK5), MEK kinase 5, MEKK5, MAP/ERK kinase kinase 5.

ASK1 is a member of the large mitogen-activated protein kinase kinasekinase (“MAP3K”) family. ASK1 activation and signaling are associated with broad range of diseases. Compounds that inhibit ASK1 are desired for use in the treatment of ASK1 mediated conditions.

Compounds that inhibit ASK1 are desired for use in the treatment of Nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis is a liver disease with an etiological constellation characterized by macrovesicular hepatic steatosis, inflammation hepatocyte ballooning and fibrosis. Currently, there is no approved pharmaceutical medicament specifically for the treatment of nonalcoholic steatohepatitis. There is a need for pharmaceutical medicaments to offer additional treatment options for patients suffering from nonalcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD), comprising several liver diseases including NAFL and NASH, which is the most frequent liver disease world-wide, is a clinical manifestation of overweight and metabolic syndrome. NAFL is a chronic disease that can last several decades and is characterized by predominant macrovesicular steatosis of the liver. The prevalence of NAFL is increasing globally. NASH is an acronym that stands for Non-Alcoholic SteatoHepatitis. It is the most severe form of NAFLD and is characterized by the presence of an abnormal accumulation of fat in the liver which in some individuals can progress to liver cell injury (hepatocellular ballooning) and inflammation. A significant number of NAFL patients develop non-alcoholic steatohepatitis (NASH), fibrosis and subsequently hepatocellular carcinoma (HCC). Hepatocellular ballooning and inflammation

– sometimes called necroinflammation– are commonly considered as the drivers of disease progression, or as the underlying causes of the disease. As NASH evolves, over time it can result in excessive scarring in the liver (fibrosis), a natural response to injury which can lead to liver cirrhosis or liver cancer.

Clearly there remains a significant unmet need for novel therapeutic agents as to target NASH progression into cirrhosis and HCC. The object of the present invention is therefore to provide novel treatment agents to this end.

OBJECT OF THE INVENTION

An object of the invention is to provide compounds as inhibitors of ASK1, a process for preparation of the inhibitors, a composition containing the compounds and utility of the compounds.

SUMMARY OF THE INVENTION

The present invention discloses novel compounds of 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-4-one their pharmaceutically acceptable salts and isomers of formula I:

Formula I

Wherein;

----- indicates an optional bond

A is absent, H, C1-C6 alkyl, 5 membered or a 6 membered saturated or unsaturated carbocycle or heterocycle that may be aromatic or aliphatic, which may contain single ring or fused ring and the ring may comprise 1 to 3 heteroatom selected from the group comprising O, N, S, which may be further substituted with R1, R1R2 OH, CH3, F or Cl; -OR1, CO, -NR1R2, -SO2(CH2)n, -CHOHR1, -CONR1R2, -COR1, -CN, -CF3; SO2NR1R2, SO2R1, O(CH2)nSO2CH3,NH(CR1R2)n , NH(CH2)nR1 , CH2SO2R1, a 3 to 6 membered carbocycle, a

5 or 6 membered heterocycle containing 1 or 2 heteroatoms selected from O, N or S; the heteroatom may be oxidised;

B is absent, H, SO2, SO2(CH2)n; SO2R1, SO2(CH2)nOR1, SO2NHR1, NH2(CH2)n, CO NH2(CH2)n, NH2(CH2)n, NH2(CH2)nR1CONH2, NH2(CH2)nCN, NHCHR1CN, NHR1, SO2Me, 3 to 8 carbocyclic ring optionally substituted by R1 or R2 or R3, 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S which may be optionally substituted by R1 or R2 or R3;

Wherein (CH2)n can form a cyclic structure depending upon the number of carbon atoms;

Wherein A may be connected to the ring though R1 and B may be connected to A through R1;

X is H, CH3, (CH2)n, C1-C6 straight or branched or cyclic alkyl, CN, (CH2)CN, OH, (CH2)nOH, CF3;

R1, R2 and R3 are independently selected from the group comprising H, halo, CN, CF3, CH3, hydroxyl, C1-C6 alkyl, C1 to C6 alkoxy , C1-C6alkoxyalkyl and C1-C6cyanoalkyl, amino, SO2, SO2C1-C6 Alkyl, CH2CF3, -(CH2)nCN, -CH2OMe, -CH2SO2Me, NR4R5, CONR4R5, C1-C6 straight or branched or cyclic alkyl, C2-C6 straight or branched alkenyl, C2-C6 straight or branched alkynyl, halo-C1-C6 alkyl, C1-C6 alkyloxy; C1-C6 alkylamino, heteroalkyl, C3–C8 cycloalkyl, C3–C8cycloalkenyl, C3–C8heterocycloalkyl, C3–C8heterocycloalkenyl, carbocycyl, aryl, and heteroaryl; oxidised heteroaryl, oxidise heterocyclyl, heteroaryl or heterocyclyl that may be optionally substituted with R4 and R5;

R4 and R5 may be selected from H, C1-C6 alkyl and C3-C8 cycloalkyl, NH2, NH, C1-C6 alkyl n is 0 to 3.

DETAILED DESCRIPTION OF THE INVENTION

The present invention discloses compounds of formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts and compositions, metabolites and prodrugs thereof, for intervention in ASK 1 and for their use in treating liver diseases such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

The present invention discloses novel compounds of 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-4-one their pharmaceutically acceptable salts and isomers of formula I:

Formula I

Wherein;

----- indicates an optional bond

A is absent, H, C1-C6 alkyl, 5 membered or a 6 membered saturated or unsaturated carbocycle or heterocycle that may be aromatic or aliphatic, which may contain single ring or fused ring and the ring may comprise 1 to 3 heteroatom selected from the group comprising O, N, S, which may be further substituted with R1, R1R2 OH, CH3, F or Cl; -OR1, CO, -NR1R2, -SO2(CH2)n, -CHOHR1, -CONR1R2, -COR1, -CN, -CF3; SO2NR1R2, SO2R1, O(CH2)nSO2 CH3,NH(CR1R2)n , NH(CH2)nR1 , CH2SO2R1, a 3 to 6 membered carbocycle, a 5 or 6 membered heterocycle containing 1 or 2 heteroatoms selected from O, N or S; the heteroatom may be oxidised;

B is absent, H, SO2, SO2(CH2)n; SO2R1, SO2(CH2)nOR1, SO2NHR1, NH2(CH2)n, CO NH2(CH2)n, NH2(CH2)n, NH2(CH2)nR1CONH2, NH2(CH2)nCN, NHCHR1CN, NHR1, SO2Me, 3 to 8 carbocyclic ring optionally substituted by R1 or R2 or R3, 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S which may be optionally substituted by R1 or R2 or R3;

Wherein (CH2)n can form a cyclic structure depending upon the number of carbon atoms;

Wherein A may be connected to the ring though R1 and B may be connected to A through R1;

X is H, CH3, (CH2)n, C1-C6 straight or branched or cyclic alkyl, CN, (CH2)CN, OH, (CH2)nOH, CF3;

R1, R2 and R3 are independently selected from the group comprising H, halo, CN, CF3, CH3, hydroxyl, C1-C6 alkyl, C1 to C6 alkoxy , C1-C6alkoxyalkyl and C1-C6cyanoalkyl, amino, SO2, SO2C1-C6 Alkyl, CH2CF3, -(CH2)nCN, -CH2OMe, -CH2SO2Me, NR4R5, CONR4R5, C1-C6 straight or branched or cyclic alkyl, C2-C6 straight or branched alkenyl, C2-C6 straight or branched alkynyl, halo-C1-C6 alkyl, C1-C6 alkyloxy; C1-C6 alkylamino, heteroalkyl, C3– C8cycloalkyl, C3–C8cycloalkenyl, C3–C8heterocycloalkyl, C3–C8heterocycloalkenyl, carbocycyl, aryl, and heteroaryl; oxidised heteroaryl, oxidise heterocyclyl, heteroaryl or heterocyclyl that may be optionally substituted with R4 and R5;

R4 and R5 may be selected from H, C1-C6 alkyl and C3-C8 cycloalkyl, NH2, NH, C1-C6 alkyl n is 0 to 3.

It is understood by a person skilled in the art that H may be added or removed as per the principles of chemistry.

The compounds disclosed herein and their pharmaceutically acceptable salts can exist as single stereoisomers, racemates, and as mixtures of enantiomers and diastereomers. The compounds disclosed herein can also exist as geometric isomers. All such single stereoisomers, racemates and mixtures thereof, and geometric isomers are intended to be within the scope of the compounds disclosed herein.

Exemplary compounds of the present invention of Formula I are illustrated herein below at Table 1.

Table 1: Exemplary compounds of the present invention.

The compounds of the present invention include:

1001. 1-(6-(1H-imidazol-1-yl)pyrimidin-4-yl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1002. 1-(3-(1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1003. 1-(4-(1H-imidazol-1-yl)pyridin-2-yl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1004. 1-(6-(1H-imidazol-1-yl)pyrimidin-4-yl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)-1H-imidazol-2(3H)-one;

1005. 1-(3-(4-cyclopropyl-1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1006. 1-(3-(1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)-1H-imidazol-2(3H)-one;

1007. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4'-(methylsulfonyl)- [1,1'-biphenyl]-3-yl)imidazolidin-2-one;

1008. 1-(2-fluoro-3-(1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1009. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3- (methylsulfonyl)phenyl)imidazolidin-2-one;

1010. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-(6- (methylsulfonyl)pyridin-3-yl)phenyl)imidazolidin-2-one;

1011. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-(pyridin-4- yl)phenyl)imidazolidin-2-one;

1012. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-(1-methyl-1H- pyrazol-4-yl)phenyl)imidazolidin-2-one;

1013. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1014. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-(1- (methylsulfonyl)-1H-pyrazol-4-yl)phenyl)imidazolidin-2-one;

1015. 3'-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)-[1,1'-biphenyl]-4-carboxamide;

1016. 3'-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)-[1,1'-biphenyl]-4-carbonitrile;

1017. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4'-(trifluoromethyl)- [1,1'-biphenyl]-3-yl)imidazolidin-2-one;

1018. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6- (methylsulfonyl)pyridin-3-yl)imidazolidin-2-one;

1019. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2-methoxy-5-(6- (methylsulfonyl)pyridin-3-yl)phenyl)imidazolidin-2-one;

1020. 4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)benzenesulfonamide;

1021. 1-(2-fluoro-5-(6-(methylsulfonyl)pyridin-3-yl)phenyl)-3-(6-(4-isopropyl-4H- 1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1022. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one; 1023. 4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)benzenesulfonamide;

1024. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-phenylimidazolidin-2- one;

1025. 1-(4-(cyclopropylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1026. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-methoxy-6-methyl- 4'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)imidazolidin-2-one;

1027. 1-(6-(2-methoxyethylsulfonyl)pyridin-3-yl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1028. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3- (methylsulfonyl)imidazolidin-2-one;

1029. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-methyl-4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1030. 1-(4-hydroxyphenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)imidazolidin-2-one

1031. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2-methoxy-4-methyl- 5-(methylsulfonyl)phenyl)imidazolidin-2-one;

1032. 1-(2-fluoro-4-(methylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1033. 1-(4-(trifluoromethyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin- 2-yl)imidazolidin-2-one;

1034. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(pyridin-4- yl)imidazolidin-2-one;

1035. 4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)benzonitrile;

1036. 1-(4-(1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1037. 1-(4-(cyclopropanecarbonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1038. 1-(3-fluoro-4-(methylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1039. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- methoxyphenyl)imidazolidin-2-one;

1040. 1-(4-(4-cyclopropyl-1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1041. 1-(4-(dimethylamino)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin- 2-yl)imidazolidin-2-one;

1042. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2-methyl-4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1043. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- morpholinophenyl)imidazolidin-2-one;

1044. N-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)methanesulfonamide;

1045. 4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)-N-methylbenzenesulfonamide;

1046. N-cyclopropyl-6-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)benzo[d]thiazol-2-aminium 2,2,2-trifluoroacetate;

1047. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- ((methylsulfonyl)methyl)phenyl)imidazolidin-2-one;

1048. N-cyclopropyl-4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)benzamide;

1049. 1-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1050. 1-(4-(2-methoxyethylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1051. 1-(4-(cyclopropyl(hydroxy)methyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1052. 2-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenylamino)-2-cyclopropylacetamide;

1053. 3-(3-(6-(3-(4-(methylsulfonyl)phenyl)-2-oxoimidazolidin-1-yl)pyridin-2-yl)- 4H-1,2,4-triazol-4-yl)butanenitrile;

1054. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-methoxy-4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1055. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2-methoxy-5-methyl- 4-(methylsulfonyl)phenyl)imidazolidin-2-one;

1056. 2-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenylamino)-2-cyclopropylacetonitrile;

1057. 1-(6-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1058. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(methylsulfonyl)-3- (pyrrolidin-1-yl)phenyl)imidazolidin-2-one;

1059. 1-(3-cyclopropyl-4-(methylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1060. 1-(3-cyclopropyl-4-fluorophenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1061. 1-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1062. 1-(3-isopropyl-4-(methylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol- 3-yl)pyridin-2-yl)imidazolidin-2-one;

1063. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(methylsulfonyl)-3- (piperidin-1-yl)phenyl)imidazolidin-2-one;

1064. 1-(5-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1065. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1066. 1-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1067. 1-(4-(4-hydroxypiperidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1068. 4-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-5-methylmorpholin-3-one;

1069. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(3- methylmorpholino)phenyl)imidazolidin-2-one;

1070. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(4,4- dimethylpiperidin-1-yl)phenyl)imidazolidin-2-one;

1071. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)azetidine-3-carbonitrile;

1072. 1-(6-(4-hydroxypiperidin-1-yl)pyridin-3-yl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1073. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (morpholinosulfonyl)phenyl)imidazolidin-2-one;

1074. 1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1075. 1-(3-fluoro-4-morpholinophenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1076. 4-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-6-methylmorpholin-3-one;

1077. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(morpholine-4- carbonyl)phenyl)imidazolidin-2-one;

1078. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(2- methylmorpholino)phenyl)imidazolidin-2-one;

1079. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-methyl-4- morpholinophenyl)imidazolidin-2-one;

1080. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (morpholinomethyl)phenyl)imidazolidin-2-one;

1081. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(tetrahydro-2H- pyran-4-ylamino)phenyl)imidazolidin-2-one;

1082. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-N-methylpiperidine-4-carboxamide;

1083. 1-(4-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1084. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(1- (methylsulfonyl)piperidin-4-yl)phenyl)imidazolidin-2-one;

1085. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-((3R,5S)-3,5- dimethylmorpholino)phenyl)imidazolidin-2-one;

1086. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-((3R,5R)-3,5- dimethylmorpholino)phenyl)imidazolidin-2-one;

1087. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)piperidine-4-carbonitrile;

1088. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(3- (isopropylamino)azetidin-1-yl)phenyl)imidazolidin-2-one;

1089. 1-(4-(3-hydroxy-3-isopropylazetidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1090. 1-(4-(3-hydroxyazetidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1091. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)pyrrolidine-3-carbonitrile;

1092. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(4-methylpiperazin- 1-yl)phenyl)imidazolidin-2-one;

1093. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)azetidine-3-carboxamide;

1094. 1-(4-(3-(cyclopropylamino)azetidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1095. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)benzoyl)azetidine-3-carbonitrile;

1096. 1-(4-(3-fluoroazetidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1097. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-N,N-dimethylpiperidine-4-carboxamide;

1098. 2-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-2-morpholinoacetonitrile;

1099. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-methylimidazolidin-2- one;

1100. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(pyrrolidin-1- yl)phenyl)imidazolidin-2-one;

1101. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6-morpholinopyridin- 3-yl)imidazolidin-2-one;

1102. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2- (methylsulfonyl)pyrimidin-5-yl)imidazolidin-2-one;

1103. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2- morpholinopyrimidin-5-yl)imidazolidin-2-one;

1104. 1-(6-(1H-imidazol-1-yl)pyridin-3-yl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1105. 1-(6-(dimethylamino)pyridin-3-yl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1106. 5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)-N-methylpyridine-2-carboxamide;

1107. 1-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)azetidine-3-carbonitrile;

1108. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3- morpholinophenyl)imidazolidin-2-one;

1109. N-cyclopropyl-5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)pyridine-2-carboxamide;

1110. N-isopropyl-5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)pyridine-2-carboxamide;

1111. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(1-(4- morpholinophenyl)ethyl)imidazolidin-2-one;

1112. 1-(4-morpholinobenzyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)imidazolidin-2-one;

1113. 2-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)-2-morpholinoacetonitrile;

1114. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(1- morpholinoethyl)phenyl)imidazolidin-2-one;

1115. 1-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)azetidine-3-carboxamide;

1116. 1-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)-N-methylpiperidine-4-carboxamide;

1117. 5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)-N-(3-methoxypropyl)pyridine-2-carboxamide;

1118. 1-(6-(3-methoxypropylamino)pyridin-3-yl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1119. 1-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)-N-methylpyrrolidine-3-carboxamide;

1120. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6-(4- (methylsulfonyl)piperidin-1-yl)pyridin-3-yl)imidazolidin-2-one;

1121. 1-(6-(4-(dimethylamino)piperidin-1-yl)pyridin-3-yl)-3-(6-(4-isopropyl-4H- 1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1122. 1-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)-N-methylazetidine-3-carboxamide;

1123. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(5- (methylsulfonyl)thiophen-2-yl)imidazolidin-2-one;

1124. 1-(3,3-dimethyl-1,1-dioxido-2,3-dihydrobenzo[b]thiophen-5-yl)-3-(6-(4- isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1125. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(1-methyl-1H-indol-5- yl)imidazolidin-2-one;

1126. 1-(4-(2-(methylsulfonyl)ethoxy)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1127. 1-(1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)ethyl)-N-methylpiperidine-4-carboxamide;

1128. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)benzyl)-N-methylpiperidine-4-carboxamide;

1129. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(2-methyl-1- morpholinopropyl)phenyl)imidazolidin-2-one;

1130. (R)-1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)-N-methylpyrrolidine-3-carboxamide;

1131. (S)-1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)-N-methylpyrrolidine-3-carboxamide;

1132. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2-morpholinopyridin- 4-yl)imidazolidin-2-one;

1133. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(tetrahydrofuran-3- ylamino)phenyl)imidazolidin-2-one;

1134. 2-(1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)azetidin-3-yl)-3-methylbutanenitrile;

1135. 4-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-1-methylpiperazin-2-one;

1136. 4-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-N-methylpiperazine-1-carboxamide;

1137. 3-(4-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)piperazin-1-yl)-3-oxopropanenitrile;

1138. 1-(4-(4-fluoropiperidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1139. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(4-(3- (methylamino)oxetan-3-yl)piperidin-1-yl)phenyl)imidazolidin-2-one;

1140. 8-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-N-methyl-8-aza-bicyclo[3.2.1]octane-3-carboxamide.

The present invention includes compound of Formula II, their stereoisomers, salts and solvates thereof;

Wherein;

----- indicates an optional bond;

B is absent, H, SO2, SO2(CH2)n; SO2R1, SO2(CH2)nOR1, SO2NHR1, NH2(CH2)n, CO NH2(CH2)n, NH2(CH2)n, NH2(CH2)nR1CONH2, NH2(CH2)nCN, NHCHR1CN, NHR1, SO2Me, 3 to 8 carbocyclic ring optionally substituted by R1 or R2 or R3, 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S which may be optionally substituted by R1 or R2 or R3;

X is H, CH3, (CH2)n, C1-C6 straight or branched or cyclic alkyl, CN, (CH2)CN, OH, (CH2)nOH, CF3;

R1, R2 and R3 are independently selected from the group comprising H, halo, CN, CF3, CH3, hydroxyl, C1-C6 alkyl, C1 to C6 alkoxy , C1-C6 alkoxyalkyl and C1-C6 cyanoalkyl, amino, SO2, SO2C1-C6 Alkyl, CH2CF3, -(CH2)nCN, -CH2OMe, -CH2SO2Me, NR4R5, CONR4R5, C1-C6 straight or branched or cyclic alkyl, C2-C6 straight or branched alkenyl, C2-C6 straight or branched alkynyl, halo-C1-C6 alkyl, C1-C6 alkyloxy; C1-C6 alkylamino, heteroalkyl, C3–C8 cycloalkyl, C3–C8cycloalkenyl, C3–C8heterocycloalkyl, C3–C8heterocycloalkenyl, carbocycyl, aryl, and heteroaryl; oxidised heteroaryl, oxidise heterocyclyl, heteroaryl or heterocyclyl that may be optionally substituted with R4 and R5;

R4 and R5 may be selected from H, C1-C6 alkyl and C3-C8 cycloalkyl, NH2, NHC1-C6 alkyl Z can be CH or N;

n is 0 to 3.

The compounds of formula II, may be selected from the group comprising:

1043: 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-morpholinophenyl)imidazolidin-2-one;

1071: 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1-yl)phenyl)azetidine-3-carbonitrile;

1082: 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1-yl)phenyl)-N-methylpiperidine-4-carboxamide;

1097: 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1-yl)phenyl)-N,N-dimethylpiperidine-4-carboxamide.

The compounds of the present invention may be present as their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts and compositions, metabolites and prodrugs thereof

The pharmaceutically acceptable salts are prepared by reacting the compound of formula (I) or formula (II( with 1 to 10 equivalents of a base such as sodium hydroxide, sodium methoxide, sodium hydride, potassium t-butoxide, calcium hydroxide, magnesium hydroxide and the like, in solvents like ether, tetrahydrofuran, methanol, t-butanol, dioxane, isopropanol, ethanol etc. Mixture of solvents may also be used. Organic bases such as diethanolamine, a-phenylethylamine, benzylamine, piperidine, morpholine, pyridine, hydroxyethylpyrrolidine, hydroxyethylpiperidine, choline, guanidine, ammonium, substituted ammonium salts and aluminum salts and amino acids such as glycine, alanine, cystine, cysteine, lysine, arginine, phenylalanine etc may be used for the preparation of amino acid salts. Alternatively, acid addition salts wherever applicable are prepared by treatment with acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, p-toluenesulphonic acid, methanesulfonic acid, acetic acid, citric acid, maleic acid, salicylic acid, hydroxynaphthoic acid, ascorbic acid, palmitic acid, succinic acid, benzoic acid, benzenesulfonic acid, tartaric acid, oxalic acid and the like in solvents like ethyl acetate, ether, alcohols, acetone, tetrahydrofuran, dioxane etc. Mixture of solvents may also be used.

It should be noted that compounds of the invention may contain groups that may exist in tautomeric forms, and though one form is named, described, displayed and/or claimed herein, all the forms are intended to be inherently included in such name, description, display and/or claim.

The stereoisomers of the compounds forming part of this invention may be prepared by using reactants in their single enantiomeric form, in the process wherever possible or by conducting the reaction in the presence of reagents or catalysts in their single enantiomeric form or by resolving the mixture of stereoisomers by conventional methods. Some of the preferred methods include use of microbial resolution, resolving the diastereomeric salts formed with chiral acids such as mandelic acid, camphorsulfonic acid, tartaric acid, lactic acid and the like, wherever applicable or by using chiral bases such as brucine, cinchona alkaloids, their derivatives and the like.

Prodrugs of the compounds of formula (I) are also contemplated by this invention. A prodrug is an active or inactive compound that is modified chemically through in-vivo physiological action, such as hydrolysis, metabolism and the like, into a compound of this invention following administration of the prodrug to a patient. The suitability and techniques involved in making, using prodrugs are well known by those skilled in the art.

Various polymorphs of the compounds of the general formula (I), forming part of this invention may be prepared by crystallization of the compounds of formula (I) under different conditions. For example, using different commonly used solvents, or their mixtures for recrystallization; crystallizations at different temperatures; various modes of cooling, ranging from very fast to very slow cooling during crystallizations. Heating or melting the compounds followed by cooling gradually or immediately, one can also obtain polymorphs. The presence of polymorphs may be determined by solid probe NMR spectroscopy, IR spectroscopy, Raman spectroscopy, differential scanning calorimetry and powder X-ray diffraction or other such techniques.

Pharmaceutically acceptable solvates of the compounds of the formula (I) forming part of this invention may be prepared by conventional methods such as dissolving the compounds of the formula (I) in solvents such as water, methanol, ethanol, mixture of solvents such as acetone/water, dioxane/water, N, N-dimethylformamide/water and the like, preferably water and recrystallization by using different crystallization techniques.

The present invention also discloses a process of preparing the compounds of the present invention. The compounds of the present invention can be prepared by the general synthetic schemes 1, presented here below:

General Synthetic Scheme 1:

Wherein, Y and Y1 are CH or N;

Wherein, R6= H, F, CH3;

Wherein, R10= -CN,-CF3,-CONH2,-SO2CH3,-CH3; Wherein, R8= H, F, CH3, OCH3;

The invention also comprises as another embodiment, a composition comprising the compound of the present invention according to any one of the preceding embodiments together with a pharmaceutically acceptable diluent, excipient, and/or carrier. The compositions will include a conventional pharmaceutical carrier, excipient, and/or diluent and a compound of this disclosure as the/an active agent, and, in addition, can include carriers and adjuvants, etc. The pharmaceutically acceptable compositions will contain about 1% to about 99% by weight of a compound(s) of this disclosure, or a pharmaceutically acceptable salt thereof, and 99% to 1% by weight of a suitable pharmaceutical excipient.

Administration of the compounds of this disclosure, or their pharmaceutically acceptable salts, in pure form or in an appropriate pharmaceutical composition, can be carried out via any of the accepted modes of administration or agents for serving similar utilities. Thus, administration can be, for example, orally, nasally, parenterally (intravenous, intramuscular, or subcutaneous), topically, transdermally, intravaginally, intravesically, intracistemally, or rectally, in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms, such as for example, tablets, suppositories, pills, soft elastic and hard gelatin capsules, powders, solutions, suspensions, or aerosols, or the like, preferably in unit dosage forms suitable for simple administration of precise dosages.

Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. Solid dosage forms, as described above, can be prepared with coatings and shells, such as enteric coatings. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. Compositions for rectal administrations are, for example, suppositories that can be prepared by mixing the compounds of this disclosure with, for example, suitable non-irritating excipients or carriers. They are also be parenteral and administered as sterile powders for reconstitution into sterile injectable solutions or dispersions. Dosage forms for topical administration of a compound of this disclosure include ointments, powders, sprays, and inhalants. Ophthalmic formulations, eye ointments, powders, and solutions are also contemplated for the compounds in this disclosure. Compressed gases can be used to disperse a compound of this disclosure in aerosol form.

The compositions described above may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavoring agents.

Compounds may be administered orally or via injection at a dose of from 0.1 to 500 mg/kg per day. The dose range for adult humans is generally from 5 mg to 2 g/day. Tablets or other forms of presentation provided in discrete units may conveniently contain an amount of one or more compounds which is effective at such dosage or as a multiple of the same, for

instance, units containing 5 mg to 500 mg, usually around 10 mg to 200 mg. The amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration.

In another embodiment, the compounds of the present invention may be utilised in intervention of disorders pertaining to or related to inhibition or intervention of ASK1. Also the compounds of the present invention are expected to intervene innonalcoholic fatty liver disease (NAFLD), obesity, metabolic syndrome, or any type of diabetes, including type 1 and type 2. The compounds of as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). and other fibrotic diseases of the liver; diabetic complications such as macro (ischemic heart disease, cerebrovascular disease and peripheral vascular disease) and micro (cataract, retinopathy nephropathy neuropathy, maculopathy and glaucoma) vascular complication; inflammation such as rheumatoid arthritis and cardiovascular diseases such as atherosclerosis, restenosis, hypertension, vasospasm, and ardiac hypertrophy; and lung disorders and lung fibrosis.

The present invention also provides a pharmaceutical composition, containing one or more of the compounds of the general formula (I) as defined above, their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, metabolites, prodrugs, pharmaceutically acceptable salts, pharmaceutically acceptable solvates in combination with the usual pharmaceutically employed carriers, diluents and the like, useful for the treatment of and/or prophylaxis of liver disorders such as NASH/NAFLD, hepatic fibrosis, liver cirrhosis, steatohepatitis and the like and associated diseases like cardiovascular disease, polycystic ovary syndrome, obstructive apnoea and the like; psoriasis; lung disorders such as lung fibrosis and the like and associated diseases such as lung metastasis and the like; and diabetic complications such as diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, diabetic cataract and the like.

The examples and scheme below depict the general synthetic procedure for the compounds disclosed herein. Synthesis of the compounds of Formulae I disclosed herein, and embodiments thereof, are not limited by these examples and schemes. One skilled in the art will know that other procedures can be used to synthesize the compounds of Formulae I disclosed herein, and that the procedures described in the examples and schemes is only one such procedure. In the descriptions below, one of ordinary skill in the art would recognize that specific reaction conditions, added reagents, solvents, and reaction temperatures can be modified for the synthesis of specific compounds that fall within the scope of this disclosure. All intermediate compounds described below, for which there is no description of how to synthesize such intermediates within these examples below, are commercially available compounds unless otherwise specified.

EXPERIMENTAL SECTION:

Example 1005: 1-(3-(4-cyclopropyl-1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one

Step 1: Synthesis of2-cyclopropyl-2-oxoethyl 4-methylbenzenesulfonate

1-cyclopropylethanone (0.62 g, 1.93 mmol) was dissolved in 18 ml acetonitrile. [Hydroxy(tosyloxy)iodo]benzene (0.76 g, 1.93 mmol) was added and the reaction mixture was stirred at reflux for 4 h. The mixture was evaporated and the semi-solid residue was triturated with ether to give the title compound. Purity 92%. Brown solid, yield 0.51 g, 53%.

MS: 255.07 [M+1]

Step 2: Synthesis of 4-cyclopropyl-1H-imidazole

2-cyclopropyl-2-oxoethyl 4-methylbenzenesulfonate (0.400 g, 1.5 mmol) was dissolved in 7 ml ethylene glycol. Formamidine acetate (1.6 g, 15.3 mmol) was added and the reaction mixture was stirred at reflux for 10 h. Reaction was monitored by TLC. On completion, the reaction mass was extracted several times with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate, concentrated under reduced pressure obtained crude which was purified column chromatography; eluent 5% CH2Cl2/MeOH to afford 4-cyclopropyl-1H-imidazole as yellowish oil. Yield 0.11 g, 57%.

MS: 109.08 [M+1]

Step 3: Synthesis of 1-(3-(4-cyclopropyl-1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one

To a stirred solution of 1-(3-bromophenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one (0.05 g, 0.117 mmol) 4-cyclopropyl-1H-imidazole (0.013 g, 0.0117 mmol in DMSO (5 mL) was added CS2CO3 (0.115 g, 0.351 mmol) , reaction mass was degassed with nitrogen for 30 min. Then, CuI (3.3 mg, 0.017 mmol) and L-Proline (3.91 mg, .034 mmol) was added to it, stirred at 100°C for 16h. Reaction was monitored by TLC. On completion, reaction was diluted with water, extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulphate, concentrated under reduced pressure obtained crude which was purified column chromatography (100-200 Mesh); eluent 3% MeOH/DCM to afford 1-(3-(4-cyclopropyl-1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one (0.026g, 52%) as off white solid.

MS: 455.23 [M++1].

Examples 1002,1003,1004,1005,1006,1008,1010,1011,1012,1014,1015,1016,1017,1019,

1020, 1026,1036,1040 and 1104 were synthesized based on above synthetic scheme by changing the substituents at step 4.

Example 1010: 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-(6-(methylsulfonyl)pyridin-3-yl)phenyl)imidazolidin-2-one

Step-1: Synthesis of 5-bromo-2-(methylthio)pyridine

2

To a stirred solution of 2,5-dibromopyridine (2.0 g, 4.22 mmol) in DMF (20 mL) was added methyl mercaptan sodium salt (1.33 ml g, 4.221 mmol) (21% solution in water) and stirred at room temperature for 16h. Reaction was monitored by TLC. On completion reaction mass was concentrated under reduced pressure. Reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate, concentrated under reduced pressure obtained crude which was purified column chromatography (100-200) mesh; eluent 3% EtOAc/Hexane to afford 5-bromo-2-(methylthio)pyridine (1.5g, 87.20%) as off white solid.

MS: 203.94[M++1]

Step-2: Synthesis of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(methylthio)pyridine

To a stirred solution of 5-bromo-2-(methylthio)pyridine (1.0g, 4.899 mmol) and Bis(pinacolato)diboron (1.86 g, 7.34 mmol) in Dioxane (50 mL) was added AcOK(1.44 g, 14.69 mmol) and reaction mass was purged with nitrogen for 30 min. Then, PdCl2(dppf)DCM (0.399 g, 0.489 mmol) was added to it and stirred at 100°C for 16h. Reaction was monitored by TLC. On completion reaction mass was concentrated under reduced pressure and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate, concentrated under reduced pressure obtained crude which was purified column chromatography; eluent 5% EtOAc/Hexane to afford 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(methylthio)pyridine (0.7 g, 56.91%) as off white solid.

WE CLAIMS

1. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-4-one as inhibitors of apoptosis signal-regulating kinase 1 (“ASK1”), their pharmaceutically acceptable salts and isomers of formula I:

Formula I

Wherein;

----- indicates an optional bond

A is absent, H, C1-C6 alkyl, 5 membered or a 6 membered saturated or unsaturated carbocycle or heterocycle that may be aromatic or aliphatic, which may contain single ring or fused ring and the ring may comprise 1 to 3 heteroatom selected from the group comprising O, N, S, which may be further substituted with R1, R1R2, OH, CH3, F or Cl; -OR1, _CO, -NR1R2, -SO2(CH2)n, -CHOHR1, -CONR1R2, -COR1, -CN, -CF3; SO2NR1R2, SO2R1, O(CH2)nSO2CH3,NH(CR1R2)n , NH(CH2)nR1 , CH2SO2R1, a 3 to 6 membered carbocycle, a 5 or 6 membered heterocycle containing 1 or 2 heteroatoms selected from O, N or S; the heteroatom may be oxidised;

B is absent, H, SO2, SO2(CH2)n; SO2R1, SO2(CH2)nOR1, SO2NHR1, NH2(CH2)n, CO NH2(CH2)n, NH2(CH2)n, NH2(CH2)nR1CONH2, NH2(CH2)nCN, NHCHR1CN, NHR1, SO2Me, 3 to 8 carbocyclic ring optionally substituted by R1 or R2 or R3, 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S which may be optionally substituted by R1 or R2 or R3;

Wherein (CH2)n can form a cyclic structure depending upon the number of carbon atoms;

Wherein A may be connected to the ring though R1 and B may be connected to A through R1;

X is H, CH3, (CH2)n, C1-C6 straight or branched or cyclic alkyl, CN, (CH2)CN, OH, (CH2)nOH, CF3;

R1, R2 and R3 are independently selected from the group comprising H, halo, CN, CF3, CH3, hydroxyl, C1-C6 alkyl, C1 to C6 alkoxy , C1-C6alkoxyalkyl and C1- C6cyanoalkyl, amino, SO2, SO2C1-C6 Alkyl, CH2CF3, -(CH2)nCN, -CH2OMe, - CH2SO2Me, NR4R5, CONR4R5, C1-C6 straight or branched or cyclic alkyl, C2-C6 straight or branched alkenyl, C2-C6 straight or branched alkynyl, halo-C1-C6 alkyl, C1-C6 alkyloxy; C1-C6 alkylamino, heteroalkyl, C3–C8 cycloalkyl, C3–C8cycloalkenyl, C3–C8heterocycloalkyl, C3–C8heterocycloalkenyl, carbocycyl, aryl, and heteroaryl; oxidised heteroaryl, oxidise heterocyclyl, heteroaryl or heterocyclyl that may be optionally substituted with R4 and R5;

R4 and R5 may be selected from H, C1-C6 alkyl and C3-C8 cycloalkyl, NH2, NH, C1- C6 alkyl

n is 0 to 3.

2. The compounds of formula I, as claimed in claim 1, selected from the group comprising:

1001. 1-(6-(1H-imidazol-1-yl)pyrimidin-4-yl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1002. 1-(3-(1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1003. 1-(4-(1H-imidazol-1-yl)pyridin-2-yl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1004. 1-(6-(1H-imidazol-1-yl)pyrimidin-4-yl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)-1H-imidazol-2(3H)-one;

1005. 1-(3-(4-cyclopropyl-1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1006. 1-(3-(1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)-1H-imidazol-2(3H)-one;

1007. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4'-(methylsulfonyl)- [1,1'-biphenyl]-3-yl)imidazolidin-2-one;

1008. 1-(2-fluoro-3-(1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1009. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3- (methylsulfonyl)phenyl)imidazolidin-2-one;

1010. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-(6- (methylsulfonyl)pyridin-3-yl)phenyl)imidazolidin-2-one;

1011. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-(pyridin-4- yl)phenyl)imidazolidin-2-one;

1012. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-(1-methyl-1H- pyrazol-4-yl)phenyl)imidazolidin-2-one;

1013. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1014. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-(1- (methylsulfonyl)-1H-pyrazol-4-yl)phenyl)imidazolidin-2-one;

1015. 3'-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)-[1,1'-biphenyl]-4-carboxamide;

1016. 3'-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)-[1,1'-biphenyl]-4-carbonitrile;

1017. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4'-(trifluoromethyl)- [1,1'-biphenyl]-3-yl)imidazolidin-2-one;

1018. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6- (methylsulfonyl)pyridin-3-yl)imidazolidin-2-one;

1019. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2-methoxy-5-(6- (methylsulfonyl)pyridin-3-yl)phenyl)imidazolidin-2-one;

1020. 4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)benzenesulfonamide;

1021. 1-(2-fluoro-5-(6-(methylsulfonyl)pyridin-3-yl)phenyl)-3-(6-(4-isopropyl-4H- 1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1022. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one; 1023. 4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)benzenesulfonamide;

1024. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-phenylimidazolidin-2- one;

1025. 1-(4-(cyclopropylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1026. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-methoxy-6-methyl- 4'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)imidazolidin-2-one;

1027. 1-(6-(2-methoxyethylsulfonyl)pyridin-3-yl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1028. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3- (methylsulfonyl)imidazolidin-2-one;

1029. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-methyl-4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1030. 1-(4-hydroxyphenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)imidazolidin-2-one

1031. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2-methoxy-4-methyl- 5-(methylsulfonyl)phenyl)imidazolidin-2-one;

1032. 1-(2-fluoro-4-(methylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1033. 1-(4-(trifluoromethyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin- 2-yl)imidazolidin-2-one;

1034. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(pyridin-4- yl)imidazolidin-2-one;

1035. 4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)benzonitrile;

1036. 1-(4-(1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1037. 1-(4-(cyclopropanecarbonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1038. 1-(3-fluoro-4-(methylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1039. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- methoxyphenyl)imidazolidin-2-one;

1040. 1-(4-(4-cyclopropyl-1H-imidazol-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1041. 1-(4-(dimethylamino)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin- 2-yl)imidazolidin-2-one;

1042. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2-methyl-4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1043. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- morpholinophenyl)imidazolidin-2-one;

1044. N-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)methanesulfonamide;

1045. 4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)-N-methylbenzenesulfonamide;

1046. N-cyclopropyl-6-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)benzo[d]thiazol-2-aminium 2,2,2-trifluoroacetate;

1047. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- ((methylsulfonyl)methyl)phenyl)imidazolidin-2-one;

1048. N-cyclopropyl-4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)benzamide;

1049. 1-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1050. 1-(4-(2-methoxyethylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1051. 1-(4-(cyclopropyl(hydroxy)methyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1052. 2-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenylamino)-2-cyclopropylacetamide;

1053. 3-(3-(6-(3-(4-(methylsulfonyl)phenyl)-2-oxoimidazolidin-1-yl)pyridin-2-yl)- 4H-1,2,4-triazol-4-yl)butanenitrile;

1054. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-methoxy-4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1055. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2-methoxy-5-methyl- 4-(methylsulfonyl)phenyl)imidazolidin-2-one;

1056. 2-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenylamino)-2-cyclopropylacetonitrile;

1057. 1-(6-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1058. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(methylsulfonyl)-3- (pyrrolidin-1-yl)phenyl)imidazolidin-2-one;

1059. 1-(3-cyclopropyl-4-(methylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1060. 1-(3-cyclopropyl-4-fluorophenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1061. 1-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1062. 1-(3-isopropyl-4-(methylsulfonyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol- 3-yl)pyridin-2-yl)imidazolidin-2-one;

1063. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(methylsulfonyl)-3- (piperidin-1-yl)phenyl)imidazolidin-2-one;

1064. 1-(5-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1065. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (methylsulfonyl)phenyl)imidazolidin-2-one;

1066. 1-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1067. 1-(4-(4-hydroxypiperidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1068. 4-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-5-methylmorpholin-3-one;

1069. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(3- methylmorpholino)phenyl)imidazolidin-2-one;

1070. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(4,4- dimethylpiperidin-1-yl)phenyl)imidazolidin-2-one;

1071. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)azetidine-3-carbonitrile;

1072. 1-(6-(4-hydroxypiperidin-1-yl)pyridin-3-yl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1073. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (morpholinosulfonyl)phenyl)imidazolidin-2-one;

1074. 1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1075. 1-(3-fluoro-4-morpholinophenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1076. 4-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-6-methylmorpholin-3-one;

1077. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(morpholine-4- carbonyl)phenyl)imidazolidin-2-one;

1078. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(2- methylmorpholino)phenyl)imidazolidin-2-one;

1079. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3-methyl-4- morpholinophenyl)imidazolidin-2-one;

1080. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- (morpholinomethyl)phenyl)imidazolidin-2-one;

1081. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(tetrahydro-2H- pyran-4-ylamino)phenyl)imidazolidin-2-one;

1082. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-N-methylpiperidine-4-carboxamide;

1083. 1-(4-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1084. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(1- (methylsulfonyl)piperidin-4-yl)phenyl)imidazolidin-2-one;

1085. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-((3R,5S)-3,5- dimethylmorpholino)phenyl)imidazolidin-2-one;

1086. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-((3R,5R)-3,5- dimethylmorpholino)phenyl)imidazolidin-2-one;

1087. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)piperidine-4-carbonitrile;

1088. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(3- (isopropylamino)azetidin-1-yl)phenyl)imidazolidin-2-one;

1089. 1-(4-(3-hydroxy-3-isopropylazetidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1090. 1-(4-(3-hydroxyazetidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1091. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)pyrrolidine-3-carbonitrile;

1092. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(4-methylpiperazin- 1-yl)phenyl)imidazolidin-2-one;

1093. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)azetidine-3-carboxamide;

1094. 1-(4-(3-(cyclopropylamino)azetidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1095. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)benzoyl)azetidine-3-carbonitrile;

1096. 1-(4-(3-fluoroazetidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1097. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-N,N-dimethylpiperidine-4-carboxamide;

1098. 2-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-2-morpholinoacetonitrile;

1099. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-methylimidazolidin-2- one;

1100. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(pyrrolidin-1- yl)phenyl)imidazolidin-2-one;

1101. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6-morpholinopyridin- 3-yl)imidazolidin-2-one;

1102. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2- (methylsulfonyl)pyrimidin-5-yl)imidazolidin-2-one;

1103. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2- morpholinopyrimidin-5-yl)imidazolidin-2-one;

1104. 1-(6-(1H-imidazol-1-yl)pyridin-3-yl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1105. 1-(6-(dimethylamino)pyridin-3-yl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1106. 5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)-N-methylpyridine-2-carboxamide;

1107. 1-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)azetidine-3-carbonitrile;

1108. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(3- morpholinophenyl)imidazolidin-2-one;

1109. N-cyclopropyl-5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)pyridine-2-carboxamide;

1110. N-isopropyl-5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)pyridine-2-carboxamide;

1111. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(1-(4- morpholinophenyl)ethyl)imidazolidin-2-one;

1112. 1-(4-morpholinobenzyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)imidazolidin-2-one;

1113. 2-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)-2-morpholinoacetonitrile;

1114. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(1- morpholinoethyl)phenyl)imidazolidin-2-one;

1115. 1-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)azetidine-3-carboxamide;

1116. 1-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)-N-methylpiperidine-4-carboxamide;

1117. 5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin-1- yl)-N-(3-methoxypropyl)pyridine-2-carboxamide;

1118. 1-(6-(3-methoxypropylamino)pyridin-3-yl)-3-(6-(4-isopropyl-4H-1,2,4- triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1119. 1-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)-N-methylpyrrolidine-3-carboxamide;

1120. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6-(4- (methylsulfonyl)piperidin-1-yl)pyridin-3-yl)imidazolidin-2-one;

1121. 1-(6-(4-(dimethylamino)piperidin-1-yl)pyridin-3-yl)-3-(6-(4-isopropyl-4H- 1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1122. 1-(5-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)pyridin-2-yl)-N-methylazetidine-3-carboxamide;

1123. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(5- (methylsulfonyl)thiophen-2-yl)imidazolidin-2-one;

1124. 1-(3,3-dimethyl-1,1-dioxido-2,3-dihydrobenzo[b]thiophen-5-yl)-3-(6-(4- isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-2-one;

1125. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(1-methyl-1H-indol-5- yl)imidazolidin-2-one;

1126. 1-(4-(2-(methylsulfonyl)ethoxy)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1127. 1-(1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)ethyl)-N-methylpiperidine-4-carboxamide;

1128. 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)benzyl)-N-methylpiperidine-4-carboxamide;

1129. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(2-methyl-1- morpholinopropyl)phenyl)imidazolidin-2-one;

1130. (R)-1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)-N-methylpyrrolidine-3-carboxamide; 1131. (S)-1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)-N-methylpyrrolidine-3-carboxamide; 1132. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(2-morpholinopyridin- 4-yl)imidazolidin-2-one;

1133. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(tetrahydrofuran-3- ylamino)phenyl)imidazolidin-2-one;

1134. 2-(1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)azetidin-3-yl)-3-methylbutanenitrile; 1135. 4-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-1-methylpiperazin-2-one;

1136. 4-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-N-methylpiperazine-1-carboxamide;

1137. 3-(4-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- oxoimidazolidin-1-yl)phenyl)piperazin-1-yl)-3-oxopropanenitrile; 1138. 1-(4-(4-fluoropiperidin-1-yl)phenyl)-3-(6-(4-isopropyl-4H-1,2,4-triazol-3- yl)pyridin-2-yl)imidazolidin-2-one;

1139. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(4-(3- (methylamino)oxetan-3-yl)piperidin-1-yl)phenyl)imidazolidin-2-one; 1140. 8-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-N-methyl-8-aza-bicyclo[3.2.1]octane-3-carboxamide.

3. 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)imidazolidin-4-one as claimed in claim 1, their pharmaceutically acceptable salts and isomers of formula II:

Wherein;

----- indicates an optional bond

B is absent, H, SO2, SO2(CH2)n; SO2R1, SO2(CH2)nOR1, SO2NHR1, NH2(CH2)n, CO NH2(CH2)n, NH2(CH2)n, NH2(CH2)nR1CONH2, NH2(CH2)nCN, NHCHR1CN, NHR1, SO2Me, 3 to 8 carbocyclic ring optionally substituted by R1 or R2 or R3, 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S which may be optionally substituted by R1 or R2 or R3;

X is H, CH3, (CH2)n, C1-C6 straight or branched or cyclic alkyl, CN, (CH2)CN, OH, (CH2)nOH, CF3;

R1, R2 and R3 are independently selected from the group comprising H, halo, CN, CF3, CH3, hydroxyl, C1-C6 alkyl, C1 to C6 alkoxy , C1-C6 alkoxyalkyl and C1-C6 cyanoalkyl, amino, SO2, SO2C1-C6 Alkyl, CH2CF3, -(CH2)nCN, -CH2OMe, - CH2SO2Me, NR4R5, CONR4R5, C1-C6 straight or branched or cyclic alkyl, C2-C6 straight or branched alkenyl, C2-C6 straight or branched alkynyl, halo-C1-C6 alkyl, C1- C6 alkyloxy; C1-C6 alkylamino, heteroalkyl, C3–C8 cycloalkyl, C3–C8cycloalkenyl, C3–C8heterocycloalkyl, C3–C8heterocycloalkenyl, carbocycyl, aryl, and heteroaryl; oxidised heteroaryl, oxidise heterocyclyl, heteroaryl or heterocyclyl that may be optionally substituted with R4 and R5

R4 and R5 may be selected from H, C1-C6 alkyl and C3-C8 cycloalkyl, NH2, NHC1-C6 alkyl

Z can be CH or N

n is 0 to 3.

4. The compounds of formula II, as claimed in claim 3, selected from the group comprising:

1043: 1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4- morpholinophenyl)imidazolidin-2-one;

1071: 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)azetidine-3-carbonitrile;

1082: 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-N-methylpiperidine-4-carboxamide;

1097: 1-(4-(3-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-oxoimidazolidin- 1-yl)phenyl)-N,N-dimethylpiperidine-4-carboxamide.

5. A process for preparing the compounds as claimed in claim 1, comprising the steps of:

Wherein, R6= H, F, CH3;

Wherein, R10= -CN,-CF3,-CONH2,-SO2CH3,-CH3;

Wherein, R8= H, F, CH3, OCH3;

6. A Pharmaceutical composition comprising the compounds as claimed in claim 1 along with pharmaceutically acceptable excipients.

7. The Pharmaceutical composition as claimed in claim 6, when administered as orally, nasally, parenterally (intravenous, intramuscular, or subcutaneous), topically, transdermally, intravaginally, intravesically, intracistemally, or rectally, in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms.

8. The compounds as claimed in claim 1, for their use in intervention of disorders pertaining to or related to inhibition or intervention of ASK1.

9. The compounds as claimed in claim 1, for their use in treating nonalcoholic fatty liver disease (NAFLD), obesity, metabolic syndrome, or any type of diabetes, including type 1 and type 2.

10. The compounds as claimed in claim 1, for their use in diabetic complications such as macro (ischemic heart disease, cerebrovascular disease and peripheral vascular disease) and micro (cataract, retinopathy, nephropathy, neuropathy, maculopathy and glaucoma) vascular complication; inflammation such as rheumatoid arthritis and cardiovascular diseases such as atherosclerosis, restenosis, hypertension, vasospasm, and cardiac hypertrophy; and lung disorders and lung fibrosis.