Antinociceptive and antiinflammatory activities and QSAR studies on 2-substituted-4,5-diphenyl-1 H-imidazoles

Abstract

This paper describes the pharmacological evaluation pertaining to antinociceptive (hot plate and tail flick) and antiinflammatory (based on Carrageenan-induced paw oedema) activities, and QSAR studies on 2-substituted-4,5-diphenyl-1 H-imidazoles. Compounds with phenyl substitution with –F, –Cl, –NH 2, –N(CH 3) 2, –OH and –OCH 3 at the p-position showed higher activity than the other substitutions in all the three studies. QSARs developed for the 60 and 120 s hot plate data indicate that the models for both the cases not only fit the data very well ( R 2 > 0.9, R adj 2 > 0.86 ), but also have very good predictive capability ( q 2 > 0.81). The descriptors used in the model relate to surface area, volume, dipole moment and ADME properties of the molecule. Good QSARs for the 60 and 120 s tail flick data are developed. The models fit the data well ( R 2 > 0.8, R adj 2 > 0.74 ), and in addition have good predictive capability ( q 2 > 0.66). Surface area, specifically polar surface area, HOMO and molecular connectivity index appear in the models. Very good QSAR model is developed for the antiinflammatory data ( R 2 = 0.86, R adj 2 = 0.822 and q 2 = 0.64) with aqueous solubility, number of hydrogen bond donor groups, surface area and principal moment of inertia as the molecular descriptors.