非甾体抗生育药物研究——二苯基萘乙烯类化合物的合成及其抗生育作用
STUDIES ON NON-STEROIDAL ANTIFERTILITY AGENTS——SYNTHESIS AND ANTIFERTILITY EFFECTS OF 1, 1-DIPHENYL-2-NAPHTHYL ETHYLENES
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摘要: 本文介绍用α-萘乙酸乙酯与相应的格氏试剂反应,继以酸催化脱水,得三芳基取代乙烯,然后用卤素、硝酸等处理,合成了十七个1,1-二苯基萘乙烯类化合物。所有化合物对大白鼠或家兔进行抗生育试验,发现化合物6931,70082,70083,在10mg/kg/天剂量下,口服六天,对大白鼠有100%的抗生育效果。其中化合物6931在5mg/kg/天剂量下,口服三天能完全抑制家兔生育。当分子中乙烯氢原子被卤素及硝基取代后,抗生育效果显著下降。Abstract: Seventeen 1, 1-diphenyl-2-naphthylethylenes were synthesized through Grignard reaction followed by acid catalyzed water elimination and tested for their antifertility effects in rats or rabbits. Three of them, compounds 6931, 70082, 70083, completely prevented fertility in female rats at a dose of 10 mg/kg/day by oral adiministration for six days. Compound 6931 was shown to be the most effective which caused complete inhibition of pregnancy in female rabbits at an oral dose of 5 mg/kg/day for three days. Further pharmacological studies revealed that this compound was also highly effective against implantation in female dogs and monkeys and no undesirable side effects has been found at different dosage levels. It was then subjected to clinical trials but the results were not very encouraging.It is interesting to note that the antifertility effects markedly decreased when the olefinic hydrogen in the molecule was replaced by bromine, chlorine or nitro group.
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