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Discovery of novel spiro-piperidine derivatives as highly potent and selective melanin-concentrating hormone 1 receptor antagonists |
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| Authors: | Takao Suzuki Minoru Moriya Toshihiro Sakamoto Takuya Suga Hiroyuki Kishino Hidekazu Takahashi Makoto Ishikawa Keita Nagai Yumiko Imai Etsuko Sekino Masahiko Ito Hisashi Iwaasa Akane Ishihara Shigeru Tokita Akio Kanatani Nagaaki Sato Takehiro Fukami |
| Affiliation: | 1. Department of Medicinal Chemistry, Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan;2. Department of Metabolic Disorder, Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan;3. Department of Pharmacology, Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan |
| Abstract: | Optimization of high-throughput screening hit 1a led to the identification of a novel spiro-piperidine class of melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. Compound 3c was identified as a highly potent and selective MCH-1R antagonist, which has an IC50 value of 0.09 nM at hMCH-1R. The synthesis and structure–activity relationships of the novel spiro-piperidine MCH-1R antagonists are described. |
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