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

Author(s): Dinesh Bhargava, C. Karthikeyan, N. S.H.N. Moorthy, Piyush Trivedi

Journal Name: Medicinal Chemistry

Volume 5 , Issue 5 , 2009


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Abstract:

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 (r2=0.85) was selected for further study and the resulted validation parameters of the model, cross validated correlation coefficient (q2=0.76 and pred_r2=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.

Keywords: QSAR, Piperazinyl phenylalanine, V-life, VLA-4/VCAM-1

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Article Details

VOLUME: 5
ISSUE: 5
Year: 2009
Published on: 01 March, 2012
Page: [446 - 454]
Pages: 9
DOI: 10.2174/157340609789117822
Price: $65

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