Filzen Gary F, Bratton Larry, Cheng Xue-Min, Erasga Noe, Geyer Andrew, Lee Chitase, Lu Gina, Pulaski Jim, Sorenson Roderick J, Unangst Paul C, Trivedi B K, Xu Xiangyang
Department of Chemistry, Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor, MI 48105, USA.
Bioorg Med Chem Lett. 2007 Jul 1;17(13):3630-5. doi: 10.1016/j.bmcl.2007.04.047. Epub 2007 Apr 24.
Recent literature has suggested the benefit of selective PPARdelta agonists for the treatment of atherosclerosis and other disease states associated with the metabolic syndrome. Herein we report the synthesis and structure-activity relationships of a series of novel and selective PPARdelta agonists. Our search began with identification of a novel benzothiophene template which was modified by the addition of various thiazolyl, isoxazolyl, and benzyloxy-benzyl moieties. Further elucidation of the SAR led to the identification of benzofuran and indole based templates. During the course of our research, we discovered three new chemical templates with varying degrees of affinity and potency for PPARdelta versus the PPARalpha and PPARgamma subtypes.
近期文献表明，选择性过氧化物酶体增殖物激活受体δ（PPARδ）激动剂对治疗动脉粥样硬化及其他与代谢综合征相关的疾病状态有益。在此，我们报告了一系列新型选择性PPARδ激动剂的合成及构效关系。我们的研究始于鉴定一种新型苯并噻吩模板，该模板通过添加各种噻唑基、异恶唑基和苄氧基 - 苄基部分进行修饰。对构效关系的进一步阐明导致了基于苯并呋喃和吲哚的模板的鉴定。在我们的研究过程中，我们发现了三种对PPARδ与PPARα和PPARγ亚型具有不同程度亲和力和效力的新化学模板。
