From Celecoxib to a Novel Class of Phosphodiesterase 5 Inhibitors: Trisubstituted Pyrazolines as Novel Phosphodiesterase 5 Inhibitors with Extremely High Potency and Phosphodiesterase Isozyme Selectivity.

本文采用基于配体的策略，对源自 COX-2 抑制剂塞来昔布的三取代吡唑啉骨架进行系统修饰，开发新型 PDE5 抑制剂。所获新型吡唑啉具有强效 PDE5 抑制活性且缺乏 COX-2 抑制活性。化合物 d12 活性最高，IC50 为 1 nM，比西地那非强 3 倍，并对其他 PDE 同工酶具有 >10,000 倍选择性指数。西地那非可抑...