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Design, synthesis, and evaluation of novel aryl-tetrahydropyridine PPARalpha/gamma dual agonists
Eunkyung Kim1, Chan Sun Park, Taedong Han
1Yuhan Research Institute, Drug Discovery Laboratory, 416-1, Gongse-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-902, Republic of Korea.
Abstract:
Aryl-tetrahydropyridine derivatives were prepared and their PPARalpha/gamma dual agonistic activities were evaluated. Among them, compound (S)-5b was identified as a potent PPARalpha/gamma dual agonist with an EC(50) of 1.73 and 0.64 microM in hPPARalpha and gamma, respectively. In diabetic (db/db) mice, compound (S)-5b showed good glucose lowering efficacy and favorable pharmacokinetic properties.
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