KNN-MFA-guided 3D-QSAR on Some PDE4 Inhibitors of Benzylamine derivatives For Chronic Obstructive Pulmonary Disease

Abstract

Benzylamine derivatives have recently been demonstrated interesting potential as the treatment for chronic obstructive pulmonary disease via interaction with the PDE4 enzymes. To understand the necessity around the nucleus k-nearest-neighbour molecular field analysis-based 3D-QSAR analysis was performed on a series of 47 compounds. The 3D-QSAR studies were performed using stepwise variable selection k-nearest-neighbour molecular field analysis approach; a leave-one-out cross-validated correlation coefficient (q2) of 0.8805 and a predicted r2 for the external test (pred_r2) of 0.6677 were obtained. Points generated in k-nearest-neighbour molecular field analysis 3D-QSAR model were S_1789 (-0.0023, -0.0021), E_14 (0.0271, 0.03699). Results showed positive range indicating that positive electrostatic potential is favourable for increase in the activity and hence a less electronegative substituent group is preferred in lattice point 14 (around R1). Negative range indicates that negative steric potential is favourable for increase in the activity and hence less bulky substituent group is preferred at lattice point. The information rendered by 3D-QSAR models lead to a better understanding of structural requirements for PDE4 inhibitors and help in the design of novel potent molecules.