新型吡唑并[3,4-d]嘧啶-4-酮类PDE5抑制剂的合成及其活性研究  

Synthesis and Biological Evaluation of Novel Pyrazolo[3,4-d]pyrimidin-4-one Derivatives as PDE5 Inhibitors

作　　者：朱玉岚[1] 刘玉乾 黄险峰[2] ZHU Yu-lan;LIU Yu-qian;HUANG Xian-feng(School of Petrochemical Engineering,Changzhou University,Changzhou 213164,China;School of Pharmacy&School of Pharmacy Biological and Food Engineering,Changzhou University,Changzhou 213164,China)

机构地区：[1]常州大学石油化工学院,江苏常州213164 [2]常州大学药学院生物与食品工程学院,江苏常州213164

出　　处：《化学试剂》2023年第11期134-139,共6页Chemical Reagents

摘　　要：设计并合成了一系列以吡唑并[3,4-d]嘧啶-4-酮为母核的PDE5抑制剂。通过放射性同位素法测定了其对PDE5的抑制活性,并计算半数有效抑制浓度(IC_(50)),随后对目标化合物进行了PDEs亚型选择性评价。化合物结构经核磁共振及质谱表征确认。活性评价结果显示,所合成的化合物对PDE5均具有一定的抑制活性,其中6-苄基-1-(4-苯基丁基)-1,5-二氢-4 H-吡唑并[3,4-d]嘧啶-4-酮表现出最强的PDE5抑制活性,其IC_(50)达到90 nmol/L,具有发展成为PDE5抑制剂的潜力。A series of pyrazolo[3,4-d]pyrimidin-4-ketone derivatives were designed and synthesized as PDE5 inhibitors,and their inhibitory activities were evaluated by the isotopic tracer method.The PDEs selectivity of the target compound was also investigated.The chemical structures were characterized by ^(1)HNMR and ESI-MS.All of compounds showed inhibitory activities on PDE5,in which 6-benzyl-1-(4-phenylbutyl)-1,5-dihydro-4 H-pyrazolo[3,4-d]pyrimidin-4-ketone exhibited the most potent inhibitory activity(IC_(50) for PDE5:90 nmol/L).Therefore,it has the potential to develop into PDE5 inhibitor.

关 键 词：PDE5 抑制剂 吡唑并[3 4-d]嘧啶-4-酮 合成 分子对接 

分 类 号：O62[理学—有机化学]