PHENYLAMINO-ACETIC ACID 1-(PYRIDIN-4-YL)-METHYLIDENE-HYDRAZIDE DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF G PROTEIN-COUPLED RECEPTOR KINASES FOR THE TREATMENT OF EYE DISEASES

摘要

Hydrazide compounds with GPCR desensitization inhibitory activity are provided that may be used to influence, inhibit or reduce the action of a G-protein receptor kinase. Pharmaceutical compositions including therapeutically effective amounts of the hydrazide compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions controlled or influenced by GPCRs are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer osteoporosis and glaucoma are also provided. (Formula (I)). A is selected from a heteroaryl group (i): wherein X1, X2, X3 and X4 are, independently, CH, O, S or N-R6, with the proviso that at least one of X2 or X3 is O, S or N-R6; and a heteroaryl group (ii): wherein X5 and X9 are CH or C-halogen, X6 and X8 are CH, and X7 is N, and wherein the six-membered heteroaryl group may be further fused with an unsubstituted six-member aryl group; R1, R2, R3, R4, and R5 are, independently, hydrogen; halogen; C1-C4 alkyl; amino; nitro; cyano; heteroaryl; carboxy, carbonylamino; aminosulfonyl; sulfonylamino; aminoacyl; thioalkyl; sulfonyl; acyl; heterocycle; -OR; -O-C1-C4alkyl-heterocycle; -C(O)NH-C1-C4alkyl-heterocycle; -C(O)NH-heteroaryl; -C(O)NH-aryl; or carboxylamino; wherein R is C1-C4 alkyl; aryl, heteroaryl, C1-C4 alkyl aryl or C1-C4 alkyl heteroaryl; R6 is H or C1-C4 alkyl; R7 is hydrogen, C1-C4 alkyl or C1-C4 alkoxy; and X is N-R6.