Synthesis and evaluation of a novel indoledione class of long chain fatty acid elongase 6 (ELOVL6) inhibitors

  • J Med Chem. 2009 May 28;52(10):3142-5. doi: 10.1021/jm900391x.
Toshiyuki Takahashi  1 ,  Tsuyoshi Nagase ,  Takahide Sasaki ,  Akira Nagumo ,  Ken Shimamura ,  Yasuhisa Miyamoto ,  Hidefumi Kitazawa ,  Maki Kanesaka ,  Ryo Yoshimoto ,  Katsumi Aragane ,  Shigeru Tokita ,  Nagaaki Sato
Affiliations
  • 1. Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan.
PMID: 19388647 DOI: 10.1021/jm900391x
Abstract

Novel indoledione derivatives were synthesized and evaluated as long chain fatty acid elongase 6 (ELOVL6) inhibitors. Systematic optimization of an indole class of lead 1 led to the identification of potent ELOVL6 selective inhibitors. Representative inhibitor 37 showed sustained plasma exposure and good liver penetrability in mice. After oral administration, 37 potently inhibited ELOVL6 activity in the liver in mice.

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