Preparation of 7,9-dihydropurine-8-one and analogs as HSP90 inhibitors.

Abstract

Dihydropurin-8-ones of formula I [R1 = halo, hydroxy, alkoxy, SH, alkylthio, alkyl, etc.; R2 = (substituted) amino, nitrogen contg. heterocycle, etc.; R3 = H, CO2H, acyl, alkyl, benzyl, phenethyl, alkylaryl, etc.; R4 = alkylene, CO, CS, SO2, absent, etc.; R5 = alkyl, aryl, heteroaryl, etc.] are prepd. that show broad utility, e.g., in inhibiting heat shock protein 90 (HSP90) to thereby treat or prevent HSP90-mediated diseases. Thus, II was prepd., and had IC50 value of 42 μM in HER2 degrdn. assay against MCF7 breast carcinoma cells. [on SciFinder(R)]