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新型芳基四氢吡啶PPARα/γ双重激动剂的设计、合成与评价

Design, synthesis, and evaluation of novel aryl-tetrahydropyridine PPARalpha/gamma dual agonists.

作者信息

Kim Eunkyung, Park Chan Sun, Han Taedong, Bae Myung-Ho, Chong Wonee, Lee Choong Hyun, Shin Young Ah, Ahn Byung-Nak, Kim Mi Kyung, Shin Chang Yell, Son Moon Ho, Kim Jin Kwan, Moon Ho Sang, Shim Hyun Joo, Kim Eun Jung, Kim Soon Hoe, Lim Joong In, Lee Chun Ho

机构信息

Yuhan Research Institute, Drug Discovery Laboratory, 416-1, Gongse-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-902, Republic of Korea.

出版信息

Bioorg Med Chem Lett. 2008 Sep 15;18(18):4993-6. doi: 10.1016/j.bmcl.2008.08.020. Epub 2008 Aug 12.

DOI:10.1016/j.bmcl.2008.08.020
PMID:18771917
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.

摘要

制备了芳基四氢吡啶衍生物，并评估了它们的过氧化物酶体增殖物激活受体α/γ（PPARα/γ）双重激动活性。其中，化合物（S）-5b被鉴定为一种有效的PPARα/γ双重激动剂，在人PPARα和γ中的半数有效浓度（EC50）分别为1.73和0.64微摩尔。在糖尿病（db/db）小鼠中，化合物（S）-5b显示出良好的降糖效果和有利的药代动力学性质。

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