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Optimization of a pharmacophore model for 5-HT4 agonists using CoMFA and receptor based alignments

Citation

Iskander, MN and Leung, LM and Buley, T and Ayad, F and Di Iulio, J and Tan, YY and Coupar, IM, Optimization of a pharmacophore model for 5-HT4 agonists using CoMFA and receptor based alignments, European Journal of Medicinal Chemistry, 41, (1) pp. 16-26. ISSN 0223-5234 (2006) [Refereed Article]


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DOI: doi:10.1016/j.ejmech.2005.07.017

Abstract

Twenty two 5-HT4 agonists obtained from our laboratory and the recent literature were used to develop a CoMFA model to predict 5-HT4 agonist activity. Two models were produced and compared for predictivity, the first by alignments based on atom overlapping (model A) and the second by adding agonist binding site interacting points of the 5-HT4 receptor (model B). Comparison of the two models showed that the q2 value for model A was 0.564 vs. 0.582 for model B. Model B indicated that the predictive power model stems from far lower steric contributions, 0.270 compared to model A's 0.502. The dominant defining features were the electrostatic contributions for model B, 0.664 up from 0.477 in model A. The contributions from the LogP factor were minimal, 0.085 in both models. The synthesized compounds showed agonist activity at μmol level.

Item Details

Item Type:Refereed Article
Keywords:5-HT4, agonist, receptor, CoMFA, 5-hydroxytryptamine
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Pharmacology and Pharmaceutical Sciences not elsewhere classified
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Preventive Medicine
Author:Tan, YY (Dr Yean Tan)
ID Code:47841
Year Published:2006
Web of Science® Times Cited:16
Deposited By:Pharmacy
Deposited On:2007-08-01
Last Modified:2013-02-28
Downloads:0

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