Discovery of novel spiro-piperidine derivatives as highly potent and selective melanin-concentrating hormone 1 receptor antagonists

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• 作者：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 Ishiha
• 关键词：Melanin-concentrating hormone ; MCH ; MCH-1R antagonists ; Obesity
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：1 June 2009
• 年：2009
• 卷：19
• 期：11
• 页码：3072-3077
• 全文大小：865 K

文摘

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.