|
|||||
|
|
Discovery of novel diarylketoxime derivatives as selective and orally active melanin-concentrating hormone 1 receptor antagonists |
|
| Authors: | Takao Suzuki Minoru Kameda Makoto Ando Hiroshi Miyazoe Etsuko Sekino Satoru Ito Kouta Masutani Kaori Kamijo Akihiro Takezawa Minoru Moriya Masahiko Ito Junko Ito Kazuho Nakase Hiroko Matsushita Akane Ishihara Norihiro Takenaga 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;4. Department of Drug Metabolism, Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan |
| Abstract: | Optimization of the lead 2a led to the identification of a novel diarylketoxime class of melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. Our focus was directed toward improvement of hERG activity and metabolic stability. The representative derivative 4b showed potent and dose-dependent body weight reduction in diet-induced obese (DIO) C57BL/6J mice after oral administration. The synthesis and structure–activity relationships of the novel diarylketoxime MCH-1R antagonists are described. |
| Keywords: | Melanin-concentrating hormone 1 receptor Antagonist Oxime Obesity |
| 本文献已被 ScienceDirect 等数据库收录！ | |