Abstract

2D QSAR STUDY OF 4 PHENOXYPYRIMIDINE-5-CARBOXAMIDE DERIVATIVES FOR ANTIDIABETIC ACTIVITY

Garg Shivangee,* Sharma Simant, Pathak Ashish and Yadav Mithlesh

ABSTRACT

TGR5 (also known as M-BAR, GPBAR1) as G-protein coupled receptor regulates GLP-1 secretion and TGR5 shown to be responsive to bile acid, from this observation TGR5 could explain beneficial metabolic properties which coupled to high circulating level of bile acids and improve insulin sensitivity. A Quantitative structure activity relationship (QSAR) study was performed on a series of 4 phenoxypyrimidine-5-carboxamide derivatives. The compound in the selected series were characterized by molecular, steric, electrotopological descriptors. Correlation between biological activity and calculated predictors variables were established through stepwise Multiple Linear Regression Method. Models were generated using Multiple Linear Regression (MLR) method for each set of descriptors, the best multi-linear QSAR equations were obtained by the stepwise variable selection method using leave-one out cross-validation as selection criterion. In present research work for QSAR study, software such as chemdraw ultra 7.0 and chemdraw3D ultra 7.0 which is byproduct of chemsoft corporation for calculation of biological activity and for structure drawing of compounds was used. The best selected model explains that descriptors of this model such as total valence connectivity (tvc) and bend energy (be) values are negatively correlated to the biological activity of compounds. The data obtained from this present Quantitative Structure Activity Relationship study may be useful in the design of more potent substituted 4 phenoxypyrimidine-5-carboxamide derivatives.

Keywords: QSAR, TGR5, Type-2 Diabetes, Phenoxypyrimidine-5-Carboxamide.