Synthesis and biological evaluation of novel pyrrolidine acid analogs as potent dual PPARα/γ agonists

Autor:	Carrie Xu, George C. Morton, Vinayak Hosagrahara, Shung Wu, Denis E. Ryono, Jonathan Lippy, Narayanan Hariharan, Kenneth T. Locke, Xiang-Xang Ye, Wei Wang, Liqun Gu, Yi-Xin Li, Fucheng Qu, Peter T. W. Cheng, Sean S. Chen, Kevin O’Malley, Michael Cap, Robert Zahler, Tao Wang, Lori Kunselman, Charles Z. Ding, Cuixia Chu, Rebecca A. Smirk, Neil Flynn, Pratik Devasthale, Hao Zhang, Nathan Morgan, Atsu Apedo, Thomas Harrity, Lisa Zhang, Dennis Farrelly, Arthur M. Doweyko, Zhi Lai, Tim Herpin, Pathanjali Kadiyala
Rok vydání:	2015
Předmět:	Blood Glucose Pyrrolidines Stereochemistry Clinical Biochemistry Mice Obese Pharmaceutical Science Peroxisome proliferator-activated receptor Ligands Biochemistry Pyrrolidine Fasting glucose Mice Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Animals Hypoglycemic Agents PPAR alpha Molecular Biology Triglycerides Biological evaluation chemistry.chemical_classification Triglyceride Organic Chemistry Stereoisomerism PPAR gamma Diabetes Mellitus Type 2 chemistry Drug Design Molecular Medicine Female
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 25:1196-1205
ISSN:	0960-894X
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef9c9221e9206ed0e57f44f10281d7ab https://doi.org/10.1016/j.bmcl.2015.01.066 Zobrazit plný text záznamu Full Text from ScienceDirect