Suzuki Takao, Moriya Minoru, Sakamoto Toshihiro, Suga Takuya, Kishino Hiroyuki, Takahashi Hidekazu, Ishikawa Makoto, Nagai Keita, Imai Yumiko, Sekino Etsuko, Ito Masahiko, Iwaasa Hisashi, Ishihara Akane, Tokita Shigeru, Kanatani Akio, Sato Nagaaki, Fukami Takehiro
Department of Medicinal Chemistry, Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co, Ltd, Tsukuba, Ibaraki, Japan.
Bioorg Med Chem Lett. 2009 Jun 1;19(11):3072-7. doi: 10.1016/j.bmcl.2009.04.016. Epub 2009 Apr 9.
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 IC(50) value of 0.09 nM at hMCH-1R. The synthesis and structure-activity relationships of the novel spiro-piperidine MCH-1R antagonists are described.
对高通量筛选命中化合物1a进行优化，从而鉴定出一类新型的螺哌啶类黑色素浓缩激素1受体（MCH-1R）拮抗剂。化合物3c被鉴定为一种高效且具选择性的MCH-1R拮抗剂，其对人MCH-1R的IC(50)值为0.09 nM。本文描述了新型螺哌啶类MCH-1R拮抗剂的合成及其构效关系。
