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

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

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=1.7 nmol/L）不仅强于西地那非(₅₀=6.5 nmol/L)，且在大鼠模型上显示与西地那非疗效相当。

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 (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.