Design, synthesis, and pharmacological evaluation of a novel series of hormone sensitive lipase inhibitor

Publication date: 1 September 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 17
Author(s): Tomoko Ogiyama, Mitsuhiro Yamaguchi, Nobuya Kurikawa, Shoko Honzumi, Koji Terayama, Nobumi Nagaoka, Yuka Yamamoto, Takako Kimura, Daisuke Sugiyama, Shin-ichi Inoue
HSL inhibition is a promising approach to the treatment of dyslipidemia. As a result of re-optimization of lead compound 2, we identified novel compound 25a exhibiting potent inhibitory activity against HSL enzyme and cell with high selectivity for cholinesterases (AChE and BuChE). Reflecting its potent in vitro activity, compound 25a exhibited antilipolytic effect in rats at 1mg/kg p.o., which indicated that this novel compound is the most potent orally active HSL inhibitor. Moreover, compound 25a did not show bioactivation liability.

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