Design, synthesis, and pharmacological characterization of some 2‐substituted‐3‐phenyl‐quinazolin‐4(3H)‐one derivatives as phosphodiesterase inhibitors
- 11 May 2021
- journal article
- research article
- Published by Wiley in Archiv der Pharmazie
- Vol. 354 (9), e2100051
- https://doi.org/10.1002/ardp.202100051
Abstract
Some 3‐phenyl‐quinazolin‐4(3H)‐one‐2‐thioethers (3a–e, 5a,b, 7a–e, 9a–d, 10a–d, and 12) along with 2‐aminoquinazoline derivatives 13a–c were prepared and screened for their in vitro phosphodiesterase (PDE) inhibitory activity. Some compounds such as 7d,e, 9a,b,d, 10a,d, and 13b exhibited promising activity as compared with the non‐selective PDE inhibitor IBMX. This inhibitory activity was validated by molecular docking in the active site of PDE7A and PDE4 to investigate their selectivity. Furthermore, the most active compound 10d (IC50 = 1.15 μM) was tested in vivo using behavioral tests. Compound 10d was able to pass the blood–brain barrier and improve scopolamine‐induced cognitive deficits. Therefore, this core can be considered as a promising scaffold for further optimization to obtain new compounds with better PDE7A selective inhibition.Keywords
This publication has 51 references indexed in Scilit:
- Phosphodiesterase 7 inhibitor reduced cognitive impairment and pathological hallmarks in a mouse model of Alzheimer's diseaseNeurobiology of Aging, 2013
- Boron‐based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal centerFEBS Letters, 2012
- PDE 7 Inhibitors: New Potential Drugs for the Therapy of Spinal Cord InjuryPLOS ONE, 2011
- Phosphodiesterase-4D Knock-Out and RNA Interference-Mediated Knock-Down Enhance Memory and Increase Hippocampal Neurogenesis via Increased cAMP SignalingJournal of Neuroscience, 2011
- Cyclic AMP-specific PDEs: A promising therapeutic target for CNS repairTranslational Neuroscience, 2010
- Synthesis, Structural Analysis, and Biological Evaluation of Thioxoquinazoline Derivatives as Phosphodiesterase 7 InhibitorsChemMedChem, 2009
- CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as an application exampleEuropean Journal of Medicinal Chemistry, 2008
- The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injuryExperimental Neurology, 2008
- Effects of dialkoxylphenyl compounds with oxime group on macrophage function and the proliferation of lymphocytesJournal of Pharmacy and Pharmacology, 2004
- Impairment of one-trial passive avoidance learning in mice by scopolamine, scopolamine methylbromide, and physostigmineInternational Journal of Neuropharmacology, 1967