Antinociceptive and antiinflammatory activities and QSAR studies on 2-substituted-4,5-diphenyl-1H-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-1H-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 120s 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 120s 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.