17α -羟化酶/C17,20-裂解酶(P45017α )抑制剂-17-[(2' -取代的)-4' -嘧啶基]雄烯衍生物的合成及药理活性

17α -羟化酶/C_17,20-裂解酶(P450_17α )抑制剂-17-[(2' -取代的)-4' -嘧啶基]雄烯衍生物的合成及药理活性

茹呈杰, 雷小平, 凌仰之^*, 张礼和, VenkatechHundratta, AngelaBrodie

1.北京大学药学院, 北京 100083;
2.马里兰大学医学院药理和实验治疗系, 美国巴尔的摩 MD21201

收稿日期:2000-10-09 修回日期:2000-12-25 出版日期:2001-03-15 发布日期:2001-03-15
通讯作者: 凌仰之*

Syntheses and Pharmacological Activity of Some 17-[(2'-Substituted)-4'-pyrimidyl]androstene Derivatives As Inhibitors of Human 17α-Hydroxylase/C_17,20-Layse

Ru Chengjie, Lei Xiaoping, Ling Yangzhi^*, Zhang Lihe, Venkatech Hundratta, Angela Brodie

1. School of Pharmaceutical Sciences, Peking University, Beijing 100083;
2. Department of Pharmacology & Experimental Therapeutics, School of Medicine, University of Maryland, Baltimore, USA 21201

Received:2000-10-09 Revised:2000-12-25 Online:2001-03-15 Published:2001-03-15
Contact: Ling Yangzhi*

摘要/Abstract

摘要： 17-位杂环取代的雄烯衍生物可以作为人细胞色素P45017α酶的有效抑制剂,抑制体内雄激素的生物合成,在治疗良性前列腺增生(BPH)和前列腺癌方面有良好的应用前景。设计并合成了七个新的17-[(2'-取代的)-4'-嘧啶基]雄烯衍生物,化合物的结构经¹H NMR、IR和元素分析或MS谱确证。化合物的药理活性实验结果表明,化合物5对P45017α(酶有较好的抑制作用, IC50 为225 nmol·L^-1。

关键词: 良性前列腺增生BPH, 前列腺癌, 17-4'-嘧啶基-雄烯衍生物, P450_17α抑制剂

Abstract: A new compound, desmosdumotin A (1), was isolated from the roots of Desmos dumosus (Roxb.)Saff. Its chemical structure was established as 5-hydroxy-7-methoxy-8-formyl-3-benzoyl-2,6-dimethyl-2R,3S-dihydrochromone on the basis of spectral methods, including ¹H-¹H COSY, ¹H-¹³C COSY, and HMBC as well as singlecrystal X-ray analysis.

Key words: Benign prostatic hypertrophy, BPH, Prostatic cancer, 17-Pyrimidylandrostenes, P450_17α inhibitors

Supporting:

茹呈杰, 雷小平, 凌仰之^*, 张礼和, VenkatechHundratta, AngelaBrodie. 17α -羟化酶/C_17,20-裂解酶(P450_17α )抑制剂-17-[(2' -取代的)-4' -嘧啶基]雄烯衍生物的合成及药理活性[J]. .

Ru Chengjie, Lei Xiaoping, Ling Yangzhi^*, Zhang Lihe, Venkatech Hundratta, Angela Brodie . Syntheses and Pharmacological Activity of Some 17-[(2'-Substituted)-4'-pyrimidyl]androstene Derivatives As Inhibitors of Human 17α-Hydroxylase/C_17,20-Layse[J]. .

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