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Journal of Chemistry
Volume 2014 (2014), Article ID 921863, 16 pages
Research Article

Chemical Feature-Based Molecular Modeling of Urotensin-II Receptor Antagonists: Generation of Predictive Pharmacophore Model for Early Drug Discovery

1Department of Pharmacy, Banasthali University, Rajasthan 304022, India
2Department of Pharmacy, LLRM Medical College, Meerut, Uttar Pradesh 250004, India

Received 6 May 2013; Revised 19 November 2013; Accepted 3 December 2013; Published 3 February 2014

Academic Editor: Georgia Melagraki

Copyright © 2014 Anubhuti Pandey et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


For a series of 35 piperazino-phthalimide and piperazino-isoindolinone based urotensin-II receptor (UT) antagonists, a thoroughly validated 3D pharmacophore model has been developed, consisting of four chemical features: one hydrogen bond acceptor lipid (HBA_L), one hydrophobe (HY), and two ring aromatic (RA). Multiple validation techniques like CatScramble, test set prediction, and mapping analysis of advanced known antagonists have been employed to check the predictive power and robustness of the developed model. The results demonstrate that the best model, Hypo 1, shows a correlation (r) of 0.902, a root mean square deviation (RMSD) of 0.886, and the cost difference of 39.69 bits. The model obtained is highly predictive with good correlation values for both internal ( ) as well as external ( ) test set compounds. Moreover, the pharmacophore model has been used as a 3D query for virtual screening which served to detect prospective new lead compounds which can be further optimized as UT antagonists with potential for treatment of cardiovascular diseases.