Quantitative Structure Activity Relationship Studies of Piperazinyl Phenylalanine Derivatives as VLA-4/VCAM-1 Inhibitors

QSAR study was carried out for a series of piperazinyl phenylalanine derivatives exhibiting VLA-4/VCAM-1 inhibitory activity to find out the structural features responsible for the biological activity. The QSAR study was carried out on V-life Molecular Design Suite software and the derived best QSAR model by partial least square (forward) regression method showed 85.67% variation in biological activity. The statistically significant model with high correlation coefficient (r(2) = 0.85) was selected for further study and the resulted validation parameters of the model, cross validated correlation coefficient (q(2) = 0.76 and pred_r(2) = 0.42) show the model has good predictive ability. The model showed that the parameters SaaNEindex, SsClcount SlogP, and 4PathCount are highly correlated with VLA-4/VCAM-1 inhibitory activity of piperazinyl phenylalanine derivatives. The result of the study suggests that the chlorine atoms in the molecule and fourth order fragmentation patterns in the molecular skeleton favour VLA-4/VCAM-1 inhibition shown by the title compounds whereas lipophilicity and nitrogen bonded to aromatic bond are not conducive for VLA-4/VCAM-1 inhibitory activity.