唑酸作为新型强效PPARα/γ双重激动剂的设计、合成及构效关系
Design, synthesis and structure-activity relationships of azole acids as novel, potent dual PPAR alpha/gamma agonists.
作者信息
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
机构信息
Metabolic Diseases Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, USA.
出版信息
Bioorg Med Chem Lett. 2009 Mar 1;19(5):1451-6. doi: 10.1016/j.bmcl.2009.01.030. Epub 2009 Jan 15.
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 PPARalpha/gamma 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.
概述了一系列新型N-苯基取代的吡咯、1,2-吡唑和1,2,3-三唑酸类似物作为过氧化物酶体增殖物激活受体（PPAR）配体的设计、合成及构效关系。在体外结合和功能试验中，三唑酸类似物3f和4f被鉴定为有效的PPARα/γ双重激动剂。3-氧苄基三唑乙酸类似物3f在糖尿病db/db小鼠中显示出优异的降血糖和降甘油三酯作用。
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