Substituted benzamide derivatives as glucokinase (GK) activators

摘要

The present invention relates to substituted benzamide derivatives of the Formula I and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, prodrugs, metabolites, and polymorphs and can be useful for treating disease states mediated by glucokinase. Compounds disclosed herein can be used for reducing blood glucose levels and for increasing insulin secretion for treating type II diabetes. The invention also relates to processes for the preparation of the compounds of invention, pharmaceutical compositions containing the compounds, and their use.;

主权项

1. Compounds having the structure of Formula (I),their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, or diastereomers thereof, wherein X═O, CH2, S; Y═O, CH2, CR1R2, NR1, NCOR1; HET-1 is a 5- or 6-membered, C-linked heteroaryl ring containing a nitrogen atom in 2-position relative to the amide nitrogen to which the ring is attached and optionally containing 1 or 2 further ring heteroatoms independently selected from O, N and S, which ring is optionally substituted on available carbon, nitrogen and/or sulfur atom with one or more R3; Ring ‘Z’ is selected from phenyl or ‘HET-3’, wherein ‘HET-3’ is a 5- or 6-membered heteroaryl or heterocyclic ring containing 1, 2 or 3 hetero atoms independently selected from O, S and N and wherein either the phenyl or the ‘HET-3’ independently is further substituted with one or more of R3;
‘Het-2’ is selected from the following cyclic groups R3 at each occurrence is independently selected from hydrogen, halogen, cyano, optionally substituted groups selected from —NR1R2, C(1-6) alkyl, C(2-6) alkenyl, C(2-6) alkyne, C(1-6) haloalkyl, C(1-6) alkoxy, C(1-6) haloalkoxy, —C(3-6) cycloalkyl, —(CH2)p—COOR1, —(CH2)p—CONR1R2,CONHR1, perfluoroalkyl, C(1-4) alkoxyalkyl, aryl, arylalkyl, amino, aminoalkyl, alkylamino, alkylaminoalkyl, alkylC(1-4)alkoxy, wherein each of R3 when further substituted, the substituents are independently selected from amino, halo, cyano, nitro, hydroxyl, alkoxy groups; and R1 and R2 at each occurrence is independently selected from hydrogen, halogen, amino, cyano, nitro, optionally substituted groups selected from C(1-4) alkyl, C(2-4) alkenyl, C(2-4) alkynyl, C(1-4) alkoxy, C(1-4) haloalkyl groups or alternatively, when possible, R1 & R2 together with the atom to which they are attached may further form a cycloalkyl or heterocyclic ring containing heteroatoms selected from O, S and N; m=0, 1, 2; n=0, 1, 2; p=0, 1, 2.