title: PDE7-Selective and Dual Inhibitors: Advances in Chemical and Biological Research.
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.
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jankowska
authors.affiliation: Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Swierczek
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Chlon-Rzepa
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawlowski
authors.affiliation: Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Wyska
mesh_terms: D000818:Animals; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000037:antagonists & inhibitors*; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010726:Phosphodiesterase Inhibitors; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7
keywords: PDE7 inhibitors; SAR exploration; allosteric modulators; dual inhibitors; immunological diseases; inflammation; neurological
  diseases