INHIBITORS OF PROTEIN KINASES

摘要

Compounds of general Formula (I):;;wherein R1, R2, R3, Ra, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and/or the glycogen synthase kinase 3 family and are useful in preventing and/or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.

主权项

1. A method for the treatment of a proliferative disease, the method comprising administering to a subject in need of such treatment an effective amount of a compound of general Formula (I): or a pharmaceutically acceptable salt, polymorph, tautomer and stereoisomer thereof wherein: Ra is H or methyl; R1 is selected from the group consisting of: carbocyclic or —C1-6 alkyl-carbocyclic, wherein the carbocyclic group is cyclohexyl or cyclopentyl; heterocyclic or —C1-6 alkyl-heterocyclic group, wherein the heterocyclic group is piperidine, piperazine, morpholine or pyrrolidine; aryl or —C1-6 alkyl-aryl; heteroaryl or —C1-6 alkyl-heteroaryl, wherein the heteroaryl group is pyridine, thiazole or thiophene;
wherein any of the aforesaid carbocyclic, heterocyclic, aryl or heteroaryl groups may optionally be substituted by one or more groups independently selected from:halo, OH, NH2 and, for carbocyclic and heterocyclic groups, ═O; orC1-4 alkyl, —O(C1-4 alkyl), —NH(C1-4 alkyl), —NHC(O)(C1-4 alkyl), —S(C1-4 alkyl), —SO(C1-4 alkyl), —SO2(C1-4 alkyl) or —SO2NH(C1-4 alkyl) any of which may be further substituted with halo or OH; orR3, —C1-4 alkyl-R3, OR3, NHR3, —NHC1-4 alkyl-R3, —OC1-4 alkyl-R3, SR3, SOR3 or SO2R3;
wherein R3 is an aryl, heteroaryl, carbocyclic or heterocyclic group any of which may be substituted with one or more halo, C1-4 alkyl, —O(C1-4 alkyl), NH2, —NH(C1-4 alkyl), —C(O)(C1-4 alkyl), —NHC(O)(C1-4 alkyl) groups, any of which alkyl groups may be substituted with halo or OH; each R2 is independently halo, OH, NH2; or C1-4 alkyl, —O(C1-4 alkyl), —NH(C1-4 alkyl), —C(O)(C1-4 alkyl), any of which may be further substituted with halo or OH; or R4, —C1-4 alkyl-R4, OR4, NHR4, —NHC1-4 alkyl-R4, —OC1-4 alkyl-R4, SR4, SOR4 or SO2R4;
wherein R4 is an aryl, heteroaryl, carbocyclic or heterocyclic group any of which may be further substituted with one or more halo, OH, C1-4 alkyl, —O(C1-4 alkyl), NH2, —NH(C1-4 alkyl), —C(O)(C1-4 alkyl), —NHC(O)(C1-4 alkyl) groups, any of which alkyl groups may be substituted with halo or OH; and x is 0-4.