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

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, -NH2, -N(CH3)2, -OH and -OCH3 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 (R2 > 0.9, Radj2 > 0.86), but also have very good predictive capability (q2 > 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 (R2 > 0.8, Radj2 > 0.74), and in addition have good predictive capability (q2 > 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 (R2 = 0.86, Radj2 = 0.822 and q2 = 0.64) with aqueous solubility, number of hydrogen bond donor groups, surface area and principal moment of inertia as the molecular descriptors. © 2006 Elsevier Ltd. All rights reserved.