Microwave-assisted synthesis of a series of 4,5-dihydro-1H-pyrazoles endowed with selective COX-1 inhibitory potency

Abstract

More efforts have been directed towards the discovery of selective COX-1 inhibitors due to recent works highlighting the involvement of COX-1 in the pathogenesis of pain, neuroinflammation, cancer and cardiovascular disorders. In this context, this paper aims to describe 2-pyrazolines endowed with selective COX-1 inhibitory potency. An efficient microwave-assisted protocol was applied for the preparation of a series of pyrazolines, which were tested for their COX-1 and COX-2 inhibitory effects using a colorimetric assay. The cytotoxic properties of the most potent derivatives on NIH/3T3 fibroblast cells were determined using MTT method. 1-(3-Fluorophenyl)-5-(3,4-methylen-dioxyphenyl)-3-(2-thienyl)-4,5-dihydro-1H-pyrazole (2g) and 1-(3-bromophe-nyl)-5-(3,4-methylendioxyphenyl)-3-(2-thienyl)-4,5-dihydro-1H-pyrazole (2h) were determined as selective COX-1 inhibitors. According to the in silico data obtained from Schr?dinger's QikProp module, both compounds are estimated to possess favorable oral bioavailability and drug-likeness. This work could be a rational guideline for further modifications at different sites on 2-pyrazoline motif to bring out a new class of selective COX-1 inhibitors.