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

Iskander, Magdy N., Leung, Lok M., Buley, Trevor, Ayad, Fadi, Di Iulio, Juliana, Tan, Yean Y. and Coupar, Ian M. (2006). Optimization of a pharmacophore model for 5-HT4 agonists using CoMFA and receptor based alignment. . European Journal of Medicinal Chemistry,41(1):16-26.

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Title Optimization of a pharmacophore model for 5-HT4 agonists using CoMFA and receptor based alignment.
Author Iskander, Magdy N.
Leung, Lok M.
Buley, Trevor
Ayad, Fadi
Di Iulio, Juliana
Tan, Yean Y.
Coupar, Ian M.
Journal Name European Journal of Medicinal Chemistry
Publication Date 2006
Volume Number 41
Issue Number 1
eISSN 1768-3254
Start Page 16
End Page 26
Total Pages 11
Place of Publication France
Publisher Elsevier Masson
Language English
Field of Research 1115 - Pharmacology and Pharmaceutical Sciences
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.
DOI http://dx.doi.org/10.1016/j.ejmech.2005.07.017   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Description for Link Link to publisher's version
URL http://www.sciencedirect.com/science/article/pii/S0223523405002448
 
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Created: Mon, 08 Dec 2014, 14:35:34 CST by Yean Tan