Holt D A, Levy M A, Brandt M, Metcalf B W
Department of Medicinal Chemistry, Smith Kline & French Laboratories, Swedeland, PA 19479.
Steroids. 1986 Sep-Oct;48(3-4):213-22. doi: 10.1016/0039-128x(86)90004-8.
A novel A-ring pyrazole steroid, 2,3-bisaza-A-nor-1,5(10)-estradien-17 beta-ol (3), was synthesized as a potential inhibitor of steroidal NAD(P)H-dependent oxidoreductases. Compound 3 proved to be a potent inhibitor of 3(17)beta-hydroxysteroid dehydrogenase (from P. testosteroni) exhibiting a Ki of 90 +/- 20 nM. The activities of 3 alpha,20 beta-hydroxysteroid dehydrogenase (from S. hydrogenans), steroid-5 alpha-reductase (from rat prostate), and 3 alpha-hydroxysteroid dehydrogenase (from rat liver) were unaffected by pyrazole 3. Dead end inhibition studies indicate an ordered binding of cofactor prior to substrate or pyrazole inhibitor.
一种新型的A环吡唑甾体化合物，2,3-双氮杂-A-降-1,5(10)-雌二烯-17β-醇（3），被合成作为甾体NAD(P)H依赖性氧化还原酶的潜在抑制剂。化合物3被证明是3(17)β-羟基甾体脱氢酶（来自睾丸酮假单胞菌）的有效抑制剂，其Ki为90±20 nM。吡唑3对3α,20β-羟基甾体脱氢酶（来自产氢脱硫弧菌）、甾体-5α-还原酶（来自大鼠前列腺）和3α-羟基甾体脱氢酶（来自大鼠肝脏）的活性没有影响。终产物抑制研究表明，辅因子在底物或吡唑抑制剂之前有序结合。
