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Identification of a novel benzimidazole derivative as a highly potent NPY Y5 receptor antagonist with an anti-obesity profile |
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| Authors: | Yuusuke Tamura Kyouhei Hayashi Naoki Omori Yuji Nishiura Kana Watanabe Nobuyuki Tanaka Masahiko Fujioka Naoki Kouyama Akira Yukimasa Yukari Tanaka Takeshi Chiba Hideki Tanioka Hirohide Nambu Hideo Yukioka Hiroki Sato Takayuki Okuno |
| Affiliation: | 1. Medicinal Research Laboratories, Shionogi & Co., Ltd, 1-1, Futabacho 3-chome, Toyonaka, Osaka 561-0825, Japan;2. Drug Developmental Research Laboratories, Shionogi & Co., Ltd, 1-1, Futabacho 3-chome, Toyonaka, Osaka 561-0825, Japan;3. Innovative Drug Discovery Research Laboratories, Shionogi & Co., Ltd, 1-1, Futabacho 3-chome, Toyonaka, Osaka 561-0825, Japan |
| Abstract: | Optimization of HTS hit 1 for NPY Y5 receptor binding affinity, CYP450 inhibition, solubility and metabolic stability led to the identification of some orally available oxygen-linker derivatives for in vivo study. Among them, derivative 4i inhibited food intake induced by the NPY Y5 selective agonist, and chronic oral administration of 4i in DIO mice caused a dose-dependent reduction of body weight gain. |
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