Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Shengjing Hospital of China Medical University, Shenyang, China.
Eur J Med Chem. 2024 Nov 5;277:116769. doi: 10.1016/j.ejmech.2024.116769. Epub 2024 Aug 13.
Phosphodiesterases (PDEs) constitute a family of enzymes that play a pivotal role in the regulation of intracellular levels of cyclic nucleotides, including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Dysregulation of PDE activity has been implicated in diverse pathological conditions encompassing cardiovascular disorders, pulmonary diseases, and neurological disorders. Small-molecule inhibitors targeting PDEs have emerged as promising therapeutic agents for the treatment of these ailments, some of which have been approved for their clinical use. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation PDE inhibitors. The objective of this review is to provide an overview of the synthesis and clinical application of representative approved small-molecule PDE inhibitors, with the aim of offering guidance for further advancements in the development of novel PDE inhibitors.
磷酸二酯酶（PDEs）构成了一类在调节细胞内环核苷酸水平中发挥关键作用的酶，包括环腺苷酸（cAMP）和环鸟苷酸（cGMP）。PDE 活性的失调与包括心血管疾病、肺部疾病和神经疾病在内的多种病理状况有关。针对 PDE 的小分子抑制剂已成为治疗这些疾病的有前途的治疗剂，其中一些已被批准用于临床应用。尽管取得了成功，但仍然存在耐药机制和脱靶效应等挑战，因此需要不断研究开发新一代 PDE 抑制剂。本综述的目的是提供代表性已批准的小分子 PDE 抑制剂的合成和临床应用概述，旨在为新型 PDE 抑制剂的开发提供指导。
