3D-QSAR study of tyrosine and propanoic acid derivatives as PPAR alpha/gamma dual agonists using CoMSIA

作者：Verma Raman K^*; Kumar Vijay; Ghosh Prithwish; Wadhwa Lalit K

来源：Medicinal Chemistry Research, 2013, 22(1): 287-302.

DOI：10.1007/s00044-012-0003-4

• T2D
• CoMSIA
• PPARs
• Dual agonists
• Activity prediction

The peroxisome proliferator-activated receptors (PPARs) have increasingly become attractive targets for developing novel therapeutics for Type 2 Diabetes. Three dimensional-quantitative structure-activity relationship approach has been applied to a series of a-substituted 3-phenylpropanoic acid and tyrosine derivatives, reported as PPAR alpha/gamma dual agonists. Comparative molecular similarity indices analysis has been employed in correlating pharmacological data available for single enantiomer at individual receptor subtype. Three models: PPAR alpha, PPAR gamma and PPARdual-model, using sum of individual activities as dependent parameter, are developed with statistically significant r(cv)(2) %26gt; 0.5 and r(ncv)(2) %26gt; 0.9 and lower values of standard error of estimation. This information can be used to design and prediction of enantioselective novel PPAR agonists. Activities of two sets of designed new molecules have also been predicted using generated models.

• 出版日期2013-1