Three-dimensional quantitative structure activity relationships (3-D-QSAR)of antihyperglycemic agents

Citation
Ss. Kulkarni et al., Three-dimensional quantitative structure activity relationships (3-D-QSAR)of antihyperglycemic agents, BIO MED CH, 7(7), 1999, pp. 1475-1485
Citations number
28
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY
ISSN journal
09680896 → ACNP
Volume
7
Issue
7
Year of publication
1999
Pages
1475 - 1485
Database
ISI
SICI code
0968-0896(199907)7:7<1475:TQSAR(>2.0.ZU;2-L
Abstract
A three-dimensional quantitative structure activity relationship study (3-D -QSAR) was performed on a set of thiazolidinedione antihyperglycemic agents using the comparative molecular field analysis (CoMFA) method. The CoMFA m odels were derived from a training set of 53 compounds. Fifteen compounds, which were not used in model generation were used to validate the CoMFA mod els. All the compounds were superimposed to the template structure by atom- based and shape-based strategies. The SYBYL QSAR rigid body field fit was a lso used for aligning the ligands. A total of twelve different alignments w ere generated. The resulting models exhibited a good cross-validated r(cv)( 2) values (0.624-0.764) and the conventional r(2) values (0.689-0.921). A m ore robust cross-validation test using cross-validation by 2 groups (leave half out method) was performed 100 times to ascertain the predictiveness of the CoMFA models. The mean of r(cv)(2) values from 100 runs ranged from 0. 611-0.690. Few models exhibited good external predictivity. These models we re then used to define a hypothetical receptor model for antihyperglycemic agents. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.