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

Abstract

Considerable efforts have been directed towards the discovery of selective cyclooxygenase isoxyme 1 (COX-1) inhibitors due to the recent work 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 synthetic method was applied for the preparation of a series of pyrazolines, which were tested for their COX-1 and cyclooxygenase isoxyme 2 (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-methylendioxyphenyl)- 3-(2-thienyl)-4,5-dihydro-1H-pyrazole (2g) and 1-(3-bromophenyl)- 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 Schrödinger’s QikProp module, both compounds are estimated to possess favourable 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.

Keywords

• pyrazoline
• microwave heating
• cyclooxygenase-1 inhibition