Design, synthesis and structure–activity relationships of azole acids as novel, potent dual PPAR α/γ agonists

…, P Devasthale, W Wang, K O'Malley, D Farrelly…

Index: Zhang, Hao; Ryono, Denis E.; Devasthale, Pratik; Wang, Wei; O'Malley, Kevin; Farrelly, Dennis; Gu, Liqun; Harrity, Thomas; Cap, Michael; Chu, Cuixia; Locke, Kenneth; Zhang, Litao; Lippy, Jonathan; Kunselman, Lori; Morgan, Nathan; Flynn, Neil; Moore, Lisa; Hosagrahara, Vinayak; Zhang, Lisa; Kadiyala, Pathanjali; Xu, Carrie; Doweyko, Arthur M.; Bell, Aneka; Chang, Chiehying; Muckelbauer, Jodi; Zahler, Robert; Hariharan, Narayanan; Cheng, Peter T.W. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 5 p. 1451 - 1456

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Citation Number: 34

Abstract

The design, synthesis and structure–activity relationships of a novel series of N-phenyl- substituted pyrrole, 1, 2-pyrazole and 1, 2, 3-triazole acid analogs as PPAR ligands are outlined. The triazole acid analogs 3f and 4f were identified as potent dual PPARα/γ agonists both in binding and functional assays in vitro. The 3-oxybenzyl triazole acetic acid analog 3f showed excellent glucose and triglyceride lowering in diabetic db/db mice.