Synthesis and Evaluation of a Novel Indoledione Class of Long Chain Fatty Acid Elongase 6 (ELOVL6) Inhibitors
详细信息 查看全文
- 作者：Toshiyuki Takahashi ; Tsuyoshi Nagase ; Takahide Sasaki ; Akira Nagumo ; Ken Shimamura ; Yasuhisa Miyamoto ; Hidefumi Kitazawa ; Maki Kanesaka ; Ryo Yoshimoto ; Katsumi Aragane ; Shigeru Tokita ; Nagaaki Sato
- 刊名：Journal of Medicinal Chemistry
- 出版年：2009
- 出版时间：May 28, 2009
- 年：2009
- 卷：52
- 期：10
- 页码：3142-3145
- 全文大小：138K
- 年卷期：v.52,no.10(May 28, 2009)
- ISSN：1520-4804
文摘
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.