文献类型：期刊文献

英文题名：New aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein

作者：Liu, Xiujie[1,2,3,4];Huang, Xiaoli[1,2,3,4];Lin, Wanhua[1,2,3,4];Wang, Dongye[1,2,3];Diao, Yanyan[5];Li, Honglin[5];Hui, Xiaoyan[6];Wang, Yu[1,2,3,6];Xu, Aimin[1,2,3,6];Wu, Donghai[1,2,3];Ke, Ding[1,2,3]

机构：[1]Chinese Acad Sci, Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China;[2]Chinese Acad Sci, Guangzhou Inst Biomed, Inst Biol Chem, Guangzhou 510530, Guangdong, Peoples R China;[3]Chinese Acad Sci, Guangzhou Inst Hlth, Inst Biol Chem, Guangzhou 510530, Guangdong, Peoples R China;[4]Chinese Acad Sci, Grad Sch, Beijing 100864, Peoples R China;[5]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[6]Univ Hong Kong, Dept Med & Pharmacol, Hong Kong 999077, Hong Kong, Peoples R China

年份：2011

卷号：21

期号：10

起止页码：2949

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000290024200033)】；

基金：We thank National Basic Research Program of China (Grant #2010CB529706, 2010CB9455000 and 2009CB940904), the 100-talent program of Chinese Academy of Sciences, and National Natural Science Foundation (Grant #30811120429, 3097063 and 90813033) for their financial support.

语种：英文

外文关键词：alpha-FABP inhibitor; Aromatic substituted pyrazoles; Inflammatory response; Inflammation related diseases

摘要：a-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5g bound to a-FABP with an apparent K-i value below 1.0 nM, while did not inhibit h-FABP at 50 mu M and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases. (C) 2011 Elsevier Ltd. All rights reserved.