Synthesis and phosphodiesterase type-5 inhibitory activity of sildenafil analogues possessing a guanidine group in the phenyl ring
- VernacularTitle: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
- Author:
Jing SHI
;
Zheng LIU
;
Zhen WANG
;
Guanghui TIAN
;
Xiaojun YANG
;
Xuelan WANG
;
Hongbin SUN
;
Jingshan SHEN
- Publication Type:Journal Article
- Keywords:
sildenafil analogues;
guanidine group;
PDE5 inhibitor
- From:
Journal of China Pharmaceutical University
2010;41(2):112-117
- CountryChina
- Language:Chinese
-
Abstract:
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(IC_(50) =1.7 nmol/L)not only exhibited more potent PDE5 inhibitory activity than that of sildenafil (IC_(50) = 6.5 nmol/L),but also showed functional efficacy in the rat model of erection.
