Arylpiperazines as fatty acid transport protein 1 (FATP1) inhibitors with improved potency and pharmacokinetic properties

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• 作者：Tetsuyoshi Matsufuji^a ; Mika Ikeda^b ; Asuka Naito^b ; Masakazu Hirouchi^c ; Shoichi Kanda^b ; Masanori Izumi^b ; Jun Harada^b ; Tsuyoshi Shinozuka^a ; ^{shinozuka.tsuyoshi.s5@daiichisankyo.co.jp}
• 关键词：Fatty acid transport protein ; High-throughput screening ; Microsomal stability ; Arylpiperazine
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 May, 2013
• 年：2013
• 卷：23
• 期：9
• 页码：2560-2565
• 全文大小：2978 K

文摘

The discovery and optimization of a novel series of FATP1 inhibitors are described. Through the derivatization process, arylpiperazine derivatives 5k and 12a were identified as possessing potent in vitro activity against human and mouse FATP1s as well as excellent pharmacokinetic properties. In vivo evaluation of triglyceride accumulation in the liver, white gastrocnemius muscle and soleus is also described.