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Article

Quantitative Antidiabetic Activity Prediction for the Class of Guanidino- and Aminoguanidinopropionic Acid Analogs Based on Electron-Conformational Studies

Supporting Info

Aleksandr V. Marenich, Pei-Han Yong, Isaac B. Bersuker, and James E. Boggs*

Institute for Theoretical Chemistry, Department of Chemistry and Biochemistry, The University of Texas at Austin, 1 University Station A5300, Austin, Texas 78712

J. Chem. Inf. Model., 2008, 48 (3), pp 556–568

DOI: 10.1021/ci700401p

Publication Date (Web): February 16, 2008

Corresponding author phone: (512)466-9145; fax: (512)471-8696; e-mail: james.boggs@mail.utexas.edu.

Abstract

The electron-conformational method has been employed to reveal the pharmacophore (Pha) and to predict antidiabetic activity, studying 154 compounds in the class of guanidino- and aminoguanidinopropionic acid analogs. The derived Pha consists of four sites with certain electronic and topological characteristics which are represented by two oxygen atoms of the carboxyl group and two nitrogens of the guanidine group but may be substituted with any other atoms that have the same electronic and geometric features. The Pha flexibility and the influence of out-of-Pha features are described by only three model descriptors that predict the experimental activities quantitatively within experimental uncertainty for a training set of 120 compounds. The quality of the derived Pha and the corresponding quantitative model of activity has been validated (and deemed acceptable) by cross-validation including many-fold cross-validations within the training set and against an independent test set of 34 additional analogs with known experimental activities out of the training set. At last, several dozen compounds never tested experimentally have been screened theoretically using this model, and statistically significant hypoglycemic activities for a few of them are predicted.

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Published In Issue March 24, 2008
Received November 1, 2007

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Article

Quantitative Antidiabetic Activity Prediction for the Class of Guanidino- and Aminoguanidinopropionic Acid Analogs Based on Electron-Conformational Studies

Abstract

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SciFinder Links

History

Recommend & Share

Related Content

Synthesis and Biological Activity of Analogues of the Antidiabetic/Antiobesity Agent 3-Guanidinopropionic Acid: Discovery of a Novel Aminoguanidinoacetic Acid Antidiabetic Agent

Pharmacophoric Features of Biguanide Derivatives: An Electronic and Structural Analysis

Discovery of a Potent, Highly Selective, and Orally Efficacious Small-Molecule Activator of the Insulin Receptor

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