【作者】 王伟；

【导师】 王恩思；

【作者基本信息】 吉林大学 ， 生物化学与分子生物学， 2006， 硕士

【摘要】 非那雄胺(finasteride),商品名保列治,是美国默沙东公司历时15年的研究成果,1992年6月在美国获得批准后投入临床。化学名称:N-叔丁基-3-氧代-4-氮杂-5α-雄甾-1-烯-17β-酰胺(N-tertbutyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide)本品是一种Ⅱ型5α-2还原酶抑制剂,能显著降低二氢睾酮水平。大量临床研究表明,本品可使症状性前列腺增生(BPH)病人的前列腺容量减少,尿流速增加,并能改善症状。我们选择最优合成路线,相应减少反应步骤,并且使得在合成中减少昂贵反应原料的使用,合成成本显著降低。使用无毒、廉价的2,3-二氯-5,6-二氰基对苯醌(DDQ)和N,O-(三甲基硅基)三氟乙酰胺(BSTFA)代替毒性大、昂贵的苯亚硒酸酐。降低了合成工艺的毒性,减少了副反应发生并使收率有所提高。制得的目标化合物经质谱法测得分子量与理论值相符合,样品的红外光谱图与参考文献中该药的红外光谱图一致。另经核磁共振13C谱、1H谱进一步证实了其分子结构的正确性。并对非那雄胺的原料药的质量标准进行了研究,结果表明自制的非那雄胺原料药符合所规定的质量标准,确保了该产品的安全性及有效性。本文提供毒性小、比较简单和低廉的非那雄胺合成工艺,适合于工业化生产。更多还原

【Abstract】 Finasteride,brand name of which is Proscar, is the achieve- ment of 15 years of research of MSD. It is a kind of 5α-2 reducing enzyme inhibitor and was applied to clinical experience in June 1992 after receiving validation in America. Its chemical name is N-tertbut- yl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide.Finasteride belongs to the 4-azasteroid structure class of comp- ounds which can selectively and competively inhibit the activity of 5α- reducing enzyme. The course of testosterone(T) changing into dihydrotestosterone(DHT) needs the participation of this kind of nicotinamide adenine dinucleotide phosphate(NADPH) dependent enzyme. Finasteride can specially inhibit typeⅡisoenzyme of 5α-2 reducing enzyme, and the latter is mainly synthesized in parastata glandulosa. The inhibition of finasteride may cause serum DHT decreasing by 60%-80%, and prostatic DHT decreasing by 90% abo- ve. The serum prostate specific antigen(PSA) of BPH patients treat- ed with finasteride is obviously decreased, but the average ratio of thefree PSA with gross PSA is not affected. Finasteride may induce the contraction of parastata glandulosa by means of atrophy and更多还原