3D-QSAR Study of Potent Inhibitors of Phosphodiesterase-4 Using a CoMFA Approach

Abstract: Phosphodiesterase-4 (PDE4) plays an important role in treatment of asthma andchronic obstructive pulmonary disease. Thirty-one analogs displaying variable inhibition ofPDE4 were selected to develop models for establishing three-dimensional quantitativestructure-activity relationships (3D-QSAR). Comparative molecular field analysis(CoMFA) was conducted on the group of analogs to determine the structural requirementsfor potency in inhibiting PDE4. The resulting model exhibited good q² and r² values up to0.741 and 0.954 for CoMFA. The contributions from the steric and electrostatic fields were0.915 and 0.085 respectively. The 3D-QSAR model should be very useful for design ofnovel PDE 4 inhibitors.