苯环上含有胍基的西地那非类似物的合成及磷酸二酯酶5抑制活性(英文)  

Synthesis and phosphodiesterase type-5 inhibitory activity of sildenafil analogues possessing a guanidine group in the phenyl ring

作　　者：石静[1] 刘正 王震[3] 田广辉[3] 杨小军 王雪兰 孙宏斌[1] 沈敬山[2,3] 

机构地区：[1]中国药科大学新药研究中心,南京210009 [2]上海特化医药有限公司,上海201209 [3]中国科学院上海药物研究所,上海201203

出　　处：《中国药科大学学报》2010年第2期112-117,共6页Journal of China Pharmaceutical University

基　　金：supported by the National High Technology Research and Development Program of China (863 Prograsm);China National Key Hi-Tech Innovation Project for the R&D of Novel Drugs (No.2009ZX09301-001,No.2009ZX09102-056)

摘　　要：本文报道了含有胍基的西地那非类似物的合成及其磷酸二酯酶5(PDE5)抑制活性。合成了一系列新的西地那非类似物11～27,体外用[3H]cGMP SPA kit方法研究了PDE5抑制活性及选择性,并在大鼠模型上进行体内药效实验。所合成的大部分化合物显示较强的PDE5抑制活性,一些对PDE5的选择性比西地那非更强。初步讨论了该类化合物的构效关系。化合物15的活性(IC50=1.7nmol/L)不仅强于西地那非(IC50=6.5nmol/L),且在大鼠模型上显示与西地那非疗效相当。In this study,a series of new sildenafil analogues 11-27 possessing a guanidine group were synthesized to investigate their PDE5 inhibitory activity and selectivity using [3H] cGMP SPA kit in vitro and efficacy in the rat model of erection.Most of the compounds showed potent activity against PDE5,and more importantly,several compounds exhibited higher PDE5 selectivity over PDE6 than that of sildenafilStructure-activity relationship of these sildenafil analogues was also discussed.Within this series of compounds,compound 15（IC50=1.7 nmol/L） not only exhibited more potent PDE5 inhibitory activity than that of sildenafil （IC50=6.5 nmol/L）,but also showed functional efficacy in the rat model of erection.

关 键 词：西地那非类似物 胍基 磷酸二酯酶5抑制剂 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]