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International Journal of Medicinal Chemistry
Volume 2012, Article ID 452325, 13 pages
http://dx.doi.org/10.1155/2012/452325
Research Article

Pharmacophore Modelling and 3D-QSAR Studies on N šŸ‘ -Phenylpyrazinones as Corticotropin-Releasing Factor 1 Receptor Antagonists

Institute of Pharmaceutical Sciences, Kurukshetra University, Haryana, Kurukshetra 136119, India

Received 17 January 2012; Accepted 27 March 2012

Academic Editor: Armando Rossello

Copyright © 2012 Paramjit Kaur 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.

Abstract

Pharmacophore modelling-based virtual screening of compound is a ligand-based approach and is useful when the 3D structure of target is not available but a few known active compounds are known. Pharmacophore mapping studies were undertaken for a set of 50 N3-phenylpyrazinones possessing Corticotropin-releasing Factor 1 (CRF 1) antagonistic activity. Six point pharmacophores with two hydrogen bond acceptors, one hydrogen bond donor, two hydrophobic regions, and one aromatic ring as pharmacophoric features were developed. Amongst them the pharmacophore hypothesis AADHHR.47 yielded a statistically significant 3D-QSAR model with 0.803 as š‘… 2 value and was considered to be the best pharmacophore hypothesis. The developed pharmacophore model was externally validated by predicting the activity of test set molecules. The squared predictive correlation coefficient of 0.91 was observed between experimental and predicted activity values of test set molecules. The geometry and features of pharmacophore were expected to be useful for the design of selective CRF 1 receptor antagonists.