A novel series of 1,6-disubstituted pyrazolo[3,4-d]pyrimidin-7-one derivatives, 2a-h, 4a-d, 5 and 6, were successfully synthesized, which showed promising, and potent inhibition of phosphodiesterase 5 (PDE5). The inhibitory activities of 5, 4b, 2a, 2d, 2f, 4d and 4a against PDE5 were similar to that of sildenafil (100%). These compounds exhibited potent relaxant effects on isolated rat cavernosum tissue with pEC₅₀ values ranging from 8.31 to 5.16 µM. Pyrazolo[3,4-d]pyrimidin-7-one scaffolds have been rationally designed via consecutive molecular modelling studies prior to their synthesis and biological evaluation. In addition, the results of the pharmacophore-based virtual screening revealed that 1v0p_PVB might have promising activity as a PDE-5 inhibitor.

成功合成了一系列新的1,6-二取代吡唑并[3,4- d ]嘧啶-7-one衍生物2a-h，4a-d，5和6，显示出有希望的，有效的磷酸二酯酶5抑制作用。 （PDE5）。5、4b，2a，2d，2f，4d和4a对PDE5的抑制活性类似于西地那非（100％）。这些化合物对分离的大鼠海绵体组织表现出强力的松弛作用，pEC ₅₀值为8.31至5.16 µM。吡唑啉[3,4- d] pyrimidin-7-one支架在合成和生物学评估之前已经通过连续的分子建模研究进行了合理设计。此外，基于药效团的虚拟筛选结果表明1v0p_PVB作为PDE-5抑制剂可能具有良好的活性。