A Series of COX‐2 Inhibitors Endowed with NO‐Releasing Properties: Synthesis, Biological Evaluation, and Docking Analysis. (27th May 2016)

• Record Type: Journal Article
• Authors: Consalvi, Sara; Poce, Giovanna; Ragno, Rino; Sabatino, Manuela; La Motta, Concettina; Sartini, Stefania; Calderone, Vincenzo; Martelli, Alma; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo; Biava, Mariangela
• Is Part Of: ChemMedChem. Volume 11:Number 16(2016)
• Page Start: 1804
• Page End: 1811
• Publication Date: 2016-05-27
• Subjects: CINODs -- drug discovery -- inflammation -- pharmacodynamics -- COX-2 inhibitors; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600086
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Herein we report the synthesis, biological evaluation, and docking analysis of a class of cyclooxygenase‐2 (COX‐2) inhibitors with nitric oxide (NO)‐releasing properties. In an earlier study, a number of selective COX‐2 inhibitors/NO donors were developed by conjugating a diarylpyrrole scaffold endowed with selective COX‐2 inhibitory properties with various nitrooxyalkyl side chains such as esters, α‐amino esters, amides, α‐amino amides, ethers, β‐amino ethers, inverse esters, and amides. These candidates were found to have high in vitro potencies (COX‐2 inhibition at 10 μm: ≥96 %), great efficacy in determining NO‐vasorelaxing responses, and good antinociceptive activity in an abdominal writhing test. Among the compounds synthesized in the present work, derivative2 b [2‐(2‐(1‐(3‐fluorophenyl)‐2‐methyl‐5‐(4‐sulfamoylphenyl)‐1 H ‐pyrrol‐3‐yl)acetamido)ethyl nitrate] showed particularly outstanding activity, with efficacy similar to that of celecoxib even at very low concentrations. Abstract : Conjugating a COX‐2‐selective diarylpyrrole scaffold with various nitrooxyalkyl side chains endowed them with NO‐releasing properties. These compounds have high in vitro potencies at COX‐2 inhibition, NO‐vasorelaxing responses, and good antinociceptive activity. They are promising candidates as a new class of analgesic drugs.