Preparation of aminopyrimidines as kinase inhibitors.

Abstract

The title compds. I [Ht = II, III (wherein R2 = H, alkyl, cyclopropyl; R21 = H); Q = O, S, (un)substituted CH2; R31 = H or F; R32 = IV (wherein J = F or alkyl; n = 1-2; R4 = H, alkyl, cycloalkyl, etc.); R1 = (un)substituted 8-12 membered bicyclic heteroaryl contg. 1-5 heteroatoms selected from O, N and S], useful as inhibitors of Aurora protein kinases, were prepd. E.g., a multi-step synthesis of the title compd. V, starting from 4,6-dichloro-2-(methylthio)pyrimidine and 3-amino-5-methylpyrazole, was given. The exemplified compds. I were tested in various assays (data given). For example, V was found to inhibit Aurora A at > 1 nM and ≤ 2 nM Ki. The invention also provides pharmaceutically acceptable compns. comprising compds. I and methods of using I and compns. in the treatment of various disease, conditions, and disorders. [on SciFinder(R)]