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

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

Volume: 24 Issue: 7

Author(s): Agnieszka Jankowska, Artur Swierczek, Grazyna Chlon-Rzepa*, Maciej Pawlowski and Elzbieta Wyska*

Affiliation:

• Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow,Poland

• Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow,Poland

Keywords: PDE7 inhibitors, dual inhibitors, SAR exploration, allosteric modulators, inflammation, neurological diseases, immunological diseases.

Abstract: 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:

Jankowska Agnieszka, Swierczek Artur, Chlon-Rzepa Grazyna*, Pawlowski Maciej and Wyska Elzbieta*, PDE7-Selective and Dual Inhibitors: Advances in Chemical and Biological Research, Current Medicinal Chemistry 2017; 24 (7) . https://dx.doi.org/10.2174/0929867324666170116125159