Synthesis,SAR, and X-ray structure of tricyclic compounds as potent FBPase inhibitors |
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| Authors: | Tomoharu Tsukada Mizuki Takahashi Toshiyasu Takemoto Osamu Kanno Takahiro Yamane Sayako Kawamura Takahide Nishi |
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| Institution: | 1. Medicinal Chemistry Research Laboratories I, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan;2. Exploratory Research Laboratories I, Daiichi Sankyo Co., Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan |
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| Abstract: | With the aim of discovering a novel class of fructose-1,6-bisphosphatase (FBPase) inhibitors, a series of compounds based on tricyclic scaffolds was synthesized. Extensive SAR studies led to the finding of 8l with an IC50 value of 0.013 μM against human FBPase. An X-ray crystallographic study revealed that 8l bound at AMP binding sites of human liver FBPase with hydrogen bonding interactions similar to AMP. |
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