Preparation of pyridinyl-substituted pyrimidine derivatives as inhibitors of cyclin-dependently kinase (CDK).

Abstract

Title compds. I [m = 0-1; n = 0-1; A1, A2, A3 and A4 independently = C, CH or N; R1-9 independently = H, halo, (un)substituted amino, alkyl, alkoxy, aryl or cycloalkyl], and their pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates are prepd. as inhibitors of cyclin-dependently kinase (CDK). Thus, e.g., II was prepd. by Suzuki reaction of 2,4-dichloropyrimidine with (3-methoxy-4-pyridinyl)boronic acid followed by condensation reaction with 2-chloro-4-(3-methoxypyridin-4-yl)pyrimidine. Select compds. of I were tested for their inhibitory activity in CDKs kinase assays, e.g., II showed IC50 value of < 5 μM for CDK1. As inhibitor of CDK, I should prove useful for the treatment, prevention and/or amelioration of protein kinases CDKs-assocd. diseases such as cancer, inflammation, cardiac hypetrophy, and HIV. [on SciFinder(R)]