Effects of D-ring substituents on antiprogestational (antagonist) and progestational (agonist) activity of 11 beta-aryl steroids.
Effects of D-ring substituents on antiprogestational (antagonist) and progestational (agonist) activity of 11 beta-aryl steroids.
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D 环取代基对 11 β-芳基类固醇的抗孕（拮抗剂）和孕（激动剂）活性的影响。
DOI：
10.1093/humrep/9.suppl_1.32
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Petrow,V
中科院分区：
文献类型：
--
作者：
Cook,CE;Lee,YW;Wani,MC;Fail,PA;Petrow,V
Roussel-Uclaf小组发现的抗孕激素不仅是一项重大的科学进步，而且还为控制生育的新方法和癌症等疾病的新疗法开辟了道路。RU486是该系列的原型，其特点是在甾体骨架的11β-位置有ap（N,N-dlmethylaminophenyl）取代基、4,9-二烯-3- 1体系和17β-羟基-17α-丙基取代基。我们研究了在类似RU486的17β-羟基化合物中改变17α-取代基的影响，在C-17上引入孕酮侧链的影响，以及在C-17α和c -16α上进一步取代对后者化合物活性的影响。这些研究表明，d环取代基在决定该系列中激动剂/拮抗剂活性平衡方面起着重要作用。例如，17 α-乙酰氧基-17β-乙酰基取代产生了一种强效拮抗剂，而16α-乙基-17β-乙酰基取代产生了一种具有强效孕激素（激动剂）活性的化合物。这些化合物为进一步有趣和有用的生物学研究提供了机会。
The discovery of antiprogestational steroids by the Roussel-Uclaf group not only was a major scientific advance but also opened the way to new methods of fertility control and new therapies for such conditions as cancer. RU486, the prototype of the series, is distinguished by ap(N,N-dlmethylaminophenyl) substituent at the 11β- position of the steroid framework, a 4,9-dien-3-one system and 17β-hydroxy-17α-propynyl substituents. We examined the effect of varying the 17α- substituent in 17β-hydroxy compounds analogous to RU486, the effect of introducing a progesterone side chain at C-17, and the effects of further substitution at C-17α and C-16αon the activity of these latter compounds. These studies indicate an important role for D-ring substituents in determining the balance of agonist/antagonist activity in this series. For example, l7α-acetoxy-17β-acetyl substitution gave a potent antagonist, whereas 16α-ethyl-17β-acetyl substitution resulted in a compound with potent progestational (agonist) activity. The compounds present opportunities for further interesting and useful biological investigations.