2,2,2-tri-substituted acetamide derivatives as glucokinase activators, their process and pharmaceutical application

A compound of formula (I)

• or its polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof useful as glucokinase activators, wherein,
• Ring-A is selected from a group consisting of aryl, heteroaryl, heterocyclyl, cycloalkyl, wherein said group is optionally either partially or fully saturated;
• wherein said ring A is further substituted with 0 to 4 numbers of substitutions independently selected from a group consisting of alkyl, alkenyl, alkynyl, halo, mono, di or per haloalkyl, nitrile, nitro, oxo, —NR6R7, —OR6, —SR6, —S(O)pR6, —S(O)pNR6R7, —NR6S(O)pR7, —NR6C(O)R7, —OS(O)pR7, —NR6C(O)OR7, —(CR8R9)n(CO)OR6, —(CR8R9)nC(O)R6, —S(O)p(NR6)R7, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl groups and like;
• which are further optionally substituted with common substituents;
• 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, further substituted with common substituents;
• R8 and R9 are independently selected from a group consisting of hydrogen, fluorine, OR6, alkyl, perfluoroalkyl;
• X is selected from a group consisting of O, NR6 and S(O)p,
• wherein R6 is as described above;
• p=0-2;
• with a proviso that, X is not connected to another heteroatom from ring-A;
• R1 and R2 are independently selected from a group consisting of fluoro, alkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl and cycloalkylalkyl, or are combined together to form a 3-7 membered ring;
• wherein R1 and R2 are substituted with 0-4 numbers of substituents selected from halogen, nitrile, nitro, oxo, —NR6R7, —OR6, —SR6, —S(O)pR6, —S(O)pNR6R7, —NR6S(O)pR7, —NR6C(O)R7, —OS(O)pR7, —NR6C(O)OR7;
• —(CR8R9)(CO)OR6, —(CR8R9)n(CO)NR6R7, —(CR8R9)nS(O)pNR6R7, —(CR8R9)nNC(O)R6, —(CR8R9)nOR6, —(CR8R9)nNR6R7, —(CR8R9)nC(O)R6, S(O)p(N)R6, tetrazole and tetrazolylalkyl;
• which are 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;
• with the proviso that R1 and R2 are not hydrogen;
• R3 is selected from hydrogen, alkyl and perfluoroalkyl;
• Ring-B is selected from optionally substituted 4-10 membered mono or bicyclic moieties containing at least one nitrogen in the ring;
• with a 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, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, —NR6, —NR6R7, —OR6, —SR6, —S(O)pR6, —S(O)pNR6R7, —NR6S(O)pR7, —NR6C(O)R7, —OS(O)pR7, —NR6C(O)OR7, —(CR8R9)n(CO)OR6, (CR8R9)n(CO)NR6R7, —(CR8R9)nS(O)pNR6R7, —(CR8R9)nN(R6)C(O)R6, —(CR8R9)nOR6, C(R8R9)nNR6R7, C(R8R9)nCO(R6), cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalyl, heteroaryl, heteroarylalkyl, tetrazole and tetrazolylalkyl which are 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;
• wherein
• p=0-2;
• n=0-4;
• R6, R7, R8 and R9 are as described above.