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.