Preparation of purine analogs as heat shock protein 90 (HSP90) inhibitors.

Abstract

Title compds. [I; A = H, halo, cyano, N2, amino, alkyl, guanidino, amidino, perhaloalkyl, OR3, SR3, etc.; Q = (substituted) alkyl, cycloalkyl, aralkyl, aryl, heteroaryl; X = S, SO, SO2; Y = H, COR2, SO2R2, CO2R2, (substituted) alkyl, alkenyl, alkynyl, aryl, aryloxyalkyl, alicyclyl, etc.; Z = H, halo, cyano, OR3, SR3, perhaloalkyl, (substituted) alkyl, alkenyl, alkynyl, aryl, alicyclyl, aralkyl, aryloxyalkyl, alkoxyalkyl, heterocyclyl, COR2, SO2R2, guanidino, amidino, etc.; R2 = (substituted) alkyl, heteroalkyl, cycloalkyl, heterocyclyl, heteroaryl, aryl; R3 = H, (substituted) alkyl, cycloalkyl, heteroalkyl, aryl, heterocyclyl, etc.], were prepd. Thus, 6-chloro-8-(2,5-dimethoxybenzyl)-N9-butylpurine (prepn. given) was heated in a sealed tube with aq. NH3 at 100° for 48 h to give 8 -(2,5-dimethoxybenzyl)-9-butyladenine. The latter showed HSP90 binding ability with IC50 = 10 μM. [on SciFinder(R)]