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.
