Pyrrole-2-carboxamide derivatives as glucokinase activators, their process and pharmaceutical application

A compound of formula (I)

• or its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein,
• Ring A is a mono or a bicyclic ring independently selected from cycloalkyl, aryl, heteroaryl and partially/fully saturated rings thereof;
• Ring A is optionally substituted with up to 4 substituents independently selected from alkyl, alkenyl, alkynyl, halogen, mono, di or perhaloalkyl, nitrile, nitro, oxo, —NR6R7, —OR6, —S(O)pR6, —S(O)pNR6R7, —NR6S(O)pR7, —NR6C(O)R7, —OS(O)pR7, —NR6C(O)OR7, —(CR8R9)pC(O)OR6, —(CR8R9)nC(O)NR6R7—(CR8R9)nC(O)R6, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazole, tetrazolylalkyl groups;
• further, the cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally substituted with halo, straight chain or branched chain alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkylsulphonyl, nitro, cyano, —COOR6, —C(O)NR6R7, —OR6, —SR6 or —NR6R7;
• p=0-2;
• n=0-4;
• R6 and R7 are independently selected from a group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl and heterocyclylalkyl, wherein each of alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl and heterocyclylalkyl is optionally substituted with halo, straight chain or branched chain alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkylsulphonyl, nitro, cyano, —COOR6, —C(O)NR6R7—OR6, —SR6 or —NR6R7;
• R8 and R9 are independently selected from a group consisting of hydrogen, fluorine, chlorine, OR6, straight and branched chain alkyl groups, aryl, arylalkyl, perfluoroalkyl, halo, straight chain or branched chain alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkylsulphonyl, nitro, cyano, —COOR6, —C(O)NR6R7, —OR6, —SR6 and —NR6R7;
• wherein the aryl group is optionally substituted with halo, straight chain or branched chain alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkylsulphonyl, nitro, cyano, —COOR6, —C(O)NR6R7, —OR6, —SR6 or —NR6R7,
• W and Y independently represents:
• —(X)m(CR8R9)n(X)o—,
• wherein X is selected from C(O), O, S(O)p and NR6,
• R6, R8, R9 are as described herein above,
• m and o are independently either 0 or 1,
• n is selected from numbers 0-4,
• p is selected from numbers 0-2;
• Z is other than hydrogen, and is selected from a group consisting of halogen, straight or branched chain alkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, and cycloalkylalkyl, wherein each of alkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, cycloalkylalkyl is optionally substituted with up to 4 substituents independently selected from halogen, nitrile, nitro, oxo, —NR6R7, —OR6, —S(O)pR6, —S(O)pNR6R7, —NR6S(O)pR7, —NR6C(O)R7, —OS(O)pR7, —NR6C(O)OR7, —(CR8R9)nC(O)OR6, —(CR8R9)nC(O)NR6R7, —(CR8R9)nS(O)pNR6R7, —(CR8R9)nNC(O)R6, —(CR8R9)nOR6, —(CR8R9)nNR6R7, —(CR8R9)nC(O)R6, tetrazole, and tetrazolylalkyl;
• wherein, p=0-2;
• n=0-4;
• R6, R7, R8 and R9 are as described herein above;
• R1, R2 are independently selected from hydrogen, perfluoroalkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, cycloalkylalkyl, arylalkyl, heterocyclylalkyl, heteroarylalkyl, —OH, —OR6, —(CH2)nOR6, tetrazole and tetrazolylalkyl, wherein each of cycloalkyl, aryl, heterocyclyl, heteroaryl, cycloalkylalkyl, arylalkyl, heterocyclylalkyl, heteroarylalkyl, —OH, —OR6, —(CH2)nOH, —(CH2)nOR6, tetrazole and tetrazolylalkyl is further substituted with halo, straight chain or branched chain alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkylsulphonyl, nitro, cyano, —COOR6, —C(O)NR6R7, —SR6 or —NR6R7;
• wherein, n=0-4;
• R6 is as described herein above;
• R3 is selected from a group consisting of hydrogen, alkyl and perfluoroalkyl;
• Ring B is an optionally substituted moiety selected from the group consisting of:
• with the proviso that the amide nitrogen of formula (I) is not connected through any heteroatom of ring-B;
• R4 and R5 are independently selected from a group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazole, tetrazolylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, —NR6, —NR6R7, —OR6, —S(O)pR6, —S(O)pNR6R7, —NR6S(O)pR7, —NR6C(O)R7, —OS(O)pR7, —NR6C(O)OR7, —(CR8R9)nC(O)OR6, —(CR8R9)n(CO)NR6R7, —(CR8R9)nS(O)pNR6R7, —(CR8R9)n(R6)C(O)R6, —(CR8R9)nOR6, C(R8R9)nNR6R7 and C(R8R9)nCO(R6), wherein each of R4 and R5 is optionally substituted with one or more substituents selected from halo, straight chain or branched chain alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkylsulphonyl, oxo, nitro, cyano, —COOR6, —C(O)NR6R7, —OR6, —SR6 or —NR6R7;
• wherein n=0-4;
• R6, R7, R8 and R9 are as described herein above;
• in addition to R4 and R5, ring-B can be further optionally substituted with one or more substituents selected from halo, straight chain or branched chain alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkylsulphonyl, oxo, nitro, cyano, —COOR6, —C(O)NR6R7, —OR6, —SR6 or —NR6R7.