Synthesis and structure–activity relationships of thiadiazole-derivatives as potent and orally active peroxisome proliferator-activated receptors α/δ dual agonists

L Shen, Y Zhang, A Wang, E Sieber-McMaster…

Index: Shen, Lan; Zhang, Yan; Wang, Aihua; Sieber-McMaster, Ellen; Chen, Xiaoli; Pelton, Patricia; Xu, June Z.; Yang, Maria; Zhu, Peifang; Zhou, Lubing; Reuman, Michael; Hu, Zhiyong; Russell, Ronald; Gibbs, Alan C.; Ross, Hamish; Demarest, Keith; Murray, William V.; Kuo, Gee-Hong Bioorganic and Medicinal Chemistry, 2008 , vol. 16, # 6 p. 3321 - 3341

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Citation Number: 31

Abstract

Replacement of the methyl-thiazole moiety of GW501516 (a PPARδ selective agonist) with [1, 2, 4] thiadiazole gave compound 21 which unexpectedly displayed submicromolar potency as a partial agonist at PPARα in addition to the high potency at PPARδ. A structure– activity relationships study of 21 resulted in the identification of 40 as a potent and selective PPARα/δ dual agonist. Compound 40 and its close analogs represent a new series of ...