Novel triazolopyridazine derivatives as kinase inhibitors and their preparation and use in the treatment of diseases.

Abstract

The invention is directed to compds. of formula I, wherein the variables are defined as herein. The compds. of formula I are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, esp. inflammatory conditions and diseases and proliferative disorders and conditions, for example, cancers. Compds. of formula I wherein ring A is heteroaryl and heterocyclyl; R1 is (un)substituted CO-C1-6 alkyl, (un)substituted CO2-C1-6 alkyl, NH2 and derivs.; NHSO2-C1-6 alkyl and derivs., etc.; each R2 is independently H, OH, oxo, (un)substituted C0-2-alkyl-NH-CONH-C3-6 cycloalkyl-Ph and derivs., (un)substituted C0-3 alkyl-NH2 and derivs., (un)substituted C1-6 alkyl, etc.; R3 is (un)substituted aryl; each R4 is independently H, OH, halo, (un)substituted C1-4 alkyl; m is 1 and 2; n is 0, 1 and 2; and pharmaceutically acceptable salts, metabolites, isomers and prodrugs thereof, are claimed. Example compd. II was prepd. by cyclization of 1-(2,4-difluorophenyl)-2-(3-isopropyl[1,2,4]triazolo[4,3-b]pyridazin-4-yl)ethanone with N,N-dimethylformamide dimethylacetal. All the invention compds. were evaluated for their kinase inhibitory activity. [on SciFinder(R)]