PDE-7选择性和双重抑制剂：化学和生物研究进展

Title:PDE7-Selective and Dual Inhibitors: Advances in Chemical and Biological Research

Volume: 24 Issue: 7

关键词: 7型磷酸二酯酶抑制剂、双重抑制剂、特区探索、变构调节剂、炎症、神经系统性疾病、免疫性疾病

摘要: Phosphodiesterase 7 (PDE7) is an intracellular enzyme that specifically hydrolyzes the second messenger, cyclic-3’,5’-adenosine monophosphate (cAMP), into inactive noncyclic nucleotide, 5’-AMP. To date, many structurally diverse compounds with PDE7 inhibitory properties have been described, including selective PDE7 inhibitors, dual PDE4/PDE7, PDE7/PDE8, and PDE7/GSK-3 inhibitors, and non-selective PDE inhibitors with high affinity for PDE7. Inhibitors of PDE7 have provided beneficial effects in animal models of inflammatory and neurological disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and many others. This review is a comprehensive summary of the current state-of-the-art in the field of design and synthesis of PDE7 inhibitors, their physicochemical properties, biological evaluation, and structure-activity relationships as well as it highlights the updated evidence for a potential therapeutic utility of these compounds. Moreover, new approaches to obtain more effective and safer PDE7 inhibitors than those available now are presented.

Cite this article as:

PDE7-Selective and Dual Inhibitors: Advances in Chemical and Biological Research, Current Medicinal Chemistry 2017; 24 (7) . https://dx.doi.org/10.2174/0929867324666170116125159