STUDIES ON AROMATASE INHIBITORS .3. SYNTHESIS AND BIOLOGICAL EVALUATION OF [(4-BROMOBENZYL)(4-CYANOPHENYL)AMINO]AZOLES AND THEIR AZINE ANALOGS

A series of [(4-bromobenzyl)(4-cyanophenyl)amino]azoles and their azin e analogs, which have the side chain of the selective aromatase inhibi tor YM511, were synthesized and evaluated for aromatase-inhibitory act ivity (in vitro) and for pregnant mare serum gonadotropin (PMSG)-induc ed estrogen synthesis inhibitory activity (in vivo). Among these aza-h eterocycles, the pyrimidin-5-yl derivative (6a) was the most potent ar omatase inhibitor and its in vitro inhibitory activity was comparable to that of YM511. Compound 6a also showed weak inhibitory activity on aldosterone synthesis. These data indicated that the pyrimidin-5-yl mo iety is useful as a new azole fragment in place of the 4H-1,2,4-triazo l-4-yl moiety of the aromatase inhibitor YM511.