17-DESOXY ESTROGEN ANALOGS
17-DESOXY ESTROGEN ANALOGS
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DOI：
10.1021/jm00127a040
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发表时间：
1989-07-01
影响因子：
7.3
通讯作者：
TANABE, M
中科院分区：
文献类型：
--
作者：
PETERS, RH;CROWE, DF;TANABE, M
合成了一系列17-取代，17-脱氧雌三烯，并作为潜在的性交后抗生育药物进行了测试。测定了雌激素的相对结合亲和力，在大鼠体内进行了雌激素样和性交后抗生育活性的测定，并进一步对选定的候选化合物进行了猴子的雌激素样活性测试。在大鼠中，17-脱氧雌三烯衍生物8a、8b和30表现出较低的雌激素活性，同时保持了强大的抗生育活性。最初的结构修饰包括各种17-取代基和省略了17-氧官能团，这在以前被认为是有效活性所必需的。17β-乙基侧链具有最强的抗生育活性，与雌激素活性的分离率最大。7位和11位的17-脱氧乙基乙基雌烷衍生物的核修饰进一步提高了所需的活性分离，其中11-羟基部分比其他特征更能促进分离。
A series of 17-substituted, 17-desoxyestratrienes have been synthesized and tested as potential postcoital antifertility agents. Estrogen-relative binding affinities were determined, in vivo assays for estrogenic and postcoital antifertility activity were conducted in rats, and selected candidate compounds were further tested for estrogenic activity in monkeys. In the rat, the 17-desoxyestratriene derivatives 8a, 8b, and 30 have shown low estrogenic activity while retaining potent antifertility activity. Structural modifications at the outset included a variety of 17-substituents and an omission of the 17-oxygen functionality, which was previously thought to be necessary for potent activity. The 17.beta.-ethyl side chain exhibited the greatest antifertility activity with the largest separation ratio to estrogenicity. Nuclear modification of 17-desoxyethylestrane derivatives at positions 7 and 11 further increased the desired separation of activity, with the 11-hydroxy moiety enhancing separation more than other features.