Browne L J, Gude C, Rodriguez H, Steele R E, Bhatnager A
Research Department, CIBA-GEIGY Corporation, Summit, New Jersey 07901.
J Med Chem. 1991 Feb;34(2):725-36. doi: 10.1021/jm00106a038.
A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-alpha]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-alpha]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5 nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.
已发现一类新型强效、选择性非甾体芳香酶抑制剂。该系列中最有效的成员是盐酸法倔唑，即CGS 16949 A，4-(5,6,7,8-四氢咪唑并[1,5-α]吡啶-5-基)苯甲腈盐酸盐，26a。此外，还合成并评估了6,7-二氢吡咯并[1,2-c]咪唑(21a)和6,7,8,9-四氢咪唑并[1,5-α]氮杂卓(21b)类似物。CGS 16949 A对其他细胞色素P-450酶具有选择性抑制芳香酶的能力(IC50 = 4.5 nM)，口服时可抑制雌激素生成，这使其成为测试芳香酶抑制剂在包括乳腺癌在内的雌激素依赖性疾病中的潜力的合适候选药物。
