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Phosphodiesterase type 5(PDE5)is a prime drug target for treating diseases such as male erectile dysfunction and pulmonary arterial hypertension.A series of novel PDE5 inhibitors with a new scaffold of the monocyclic pyrimidin-4(3H)-one ring were developed using the structure-based discovery strategy.The most potent compound has an excellent IC50(1.6 nM)in vitro and a good efficacy in a rat model of erection,providing a potential candidate for the further development into a new drug targeting PDE5.