Peters R H, Crowe D F, Avery M A, Chong W K, Tanabe M
Bio-Organic Chemistry Laboratory, SRI International, Menlo Park, California 94025.
J Med Chem. 1989 Jul;32(7):1642-52. doi: 10.1021/jm00127a040.
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.
已合成了一系列17-取代的17-去氧雌三烯，并作为潜在的性交后抗生育剂进行了测试。测定了与雌激素相关的结合亲和力，在大鼠中进行了雌激素活性和性交后抗生育活性的体内试验，并对选定的候选化合物在猴子中进一步测试了雌激素活性。在大鼠中，17-去氧雌三烯衍生物8a、8b和30显示出低雌激素活性，同时保留了强大的抗生育活性。最初的结构修饰包括多种17-取代基以及省略17-氧官能团，而之前认为该官能团对于强效活性是必需的。17β-乙基侧链表现出最大的抗生育活性，与雌激素活性的分离比最大。17-去氧乙基雌烷衍生物在7位和11位的核修饰进一步增加了所需的活性分离，11-羟基部分比其他特征更能增强分离效果。
