| Literature DB >> 25686852 |
Hao Zhang1, Charles Z Ding1, Zhi Lai1, Sean S Chen1, Pratik Devasthale1, Tim Herpin1, George Morton1, Fucheng Qu1, Denis Ryono1, Rebecca Smirk1, Wei Wang1, Shung Wu1, Xiang-Xang Ye1, Yi-Xin Li2, Atsu Apedo2, Dennis Farrelly3, Tao Wang4, Liqun Gu3, Nathan Morgan3, Neil Flynn3, Cuixia Chu3, Lori Kunselman3, Jonathan Lippy4, Kenneth Locke4, Kevin O'Malley4, Thomas Harrity3, Michael Cap3, Lisa Zhang5, Vinayak Hosagrahara5, Pathanjali Kadiyala5, Carrie Xu5, Arthur M Doweyko6, Robert Zahler1, Narayanan Hariharan3, Peter T W Cheng1.
Abstract
The design, synthesis and structure-activity relationships of a novel series of 3,4-disubstituted pyrrolidine acid analogs as PPAR ligands is outlined. In both the 1,3- and 1,4-oxybenzyl pyrrolidine acid series, the preferred stereochemistry was shown to be the cis-3R,4S isomer, as exemplified by the potent dual PPARα/γ agonists 3k and 4i. The N-4-trifluoromethyl-pyrimidinyl pyrrolidine acid analog 4i was efficacious in lowering fasting glucose and triglyceride levels in diabetic db/db mice.Entities:
Keywords: Dual agonists; Peroxisome Proliferator-Activated Receptor; Pyrrolidine acid; Type 2 diabetes
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Year: 2015 PMID： 25686852 DOI： 10.1016/j.bmcl.2015.01.066
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823