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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。
This paper reports the synthesis and phosphodiesterase 5 (PDE5) inhibitory activity of guanidine-containing sildenafil analogs. A series of new sildenafil analogues 11-27 were synthesized. The inhibitory activity and selectivity of PDE5 were studied by [3H] cGMP SPA kit in vitro. The in vivo pharmacodynamic tests were performed in rat models. Most of the compounds synthesized showed stronger PDE5 inhibitory activity and some were more selective for PDE5 than sildenafil. The structure-activity relationship of these compounds is discussed preliminarily. Compound 15 activity (IC50 = 1.7 nmol / L) was not only stronger than sildenafil (IC50 = 6.5 nmol / L), but also showed comparable efficacy to sildenafil in a rat model.