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以去卵巢小鼠的雌激素作用维持时间为指标,探讨一系列雌二醇衍化物的构效关系。 结果表明,乙炔雌二醇的3-环戊醚衍化物(炔雌醚)的口服雌激素作用时间,显著较其母体化合物为长。但在雌二醇和乙炔雌二醇的3位碳上,以其它基团(如甲基、异丙基、丙炔基、丙烯基和乙基甲醚等)进行醚化,则均不能显著延长口服雌激素作用时间。 17α位的结构变化可明显影响雌激素的口服活性。炔雌醚17α位的乙炔基换成环戊基后,即17环戊雌二醇-3-环戊醚(ⅩⅩⅨ),雌激素作用时间更长。 雌二醇的酯类衍化物皮下注射有明显长效雌激素作用,但口服则不能显著延长作用时间。口腔(舌下)给药可能因避开胃肠道的水解和肝脏破坏,其作用时间较口服(灌胃)给药显著延长,但远不及皮下注射。 炔雌醚的17β位以脂肪酸酯化后,其作用时间与其母体相近;但如在17β位醚化后,则作用就有不同程度的降低。
The ovarian mouse estrogen maintenance time as an indicator to explore a series of estradiol derivatives structure-activity relationship. The results showed that the oral estrogen action time of ethinyl estradiol 3-cyclopentyl ether derivative (ethinylestradiol) was significantly longer than that of its parent compound. However, no significant prolongation of etherification with other groups (such as methyl, isopropyl, propynyl, propenyl and ethyl methyl ether) on the 3 carbon of estradiol and ethinyl estradiol Oral administration of estrogen time. Changes in the structure of 17α position can significantly affect the oral activity of estrogen. Ethinyl estradiol 17α-bit ethynyl replaced cyclopentyl group, namely 17 cyclopentyl estradiol-3-cyclopentyl ether (XXIX), estrogen longer duration. Estradiol ester derivatives subcutaneous injection of significant long-acting estrogen effect, but oral can not significantly extend the action time. Oral (sublingual) administration may be due to avoid gastrointestinal hydrolysis and liver damage, the role of time than oral (gavage) administration was significantly prolonged, but far less than subcutaneous injection. Ethinyl estradiol ester 17β position with fatty acids, the role of time and its mother similar; but if the 17β-etherification, the role of varying degrees of reduction.