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

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

doi:10.1016/j.bmcl.2009.04.016

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

Bioorg Med Chem Lett. 2009 Jun 1;19(11):3072-7. doi: 10.1016/j.bmcl.2009.04.016. Epub 2009 Apr 9.

Authors

Takao Suzuki¹, 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, Tsukuba, Ibaraki, Japan. [email protected]

PMID: 19403308
DOI: 10.1016/j.bmcl.2009.04.016

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 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.

MeSH terms

Cell Line
Drug Discovery
Humans
Piperidines / chemical synthesis
Piperidines / chemistry*
Piperidines / pharmacology
Receptors, Somatostatin / antagonists & inhibitors*
Receptors, Somatostatin / metabolism
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry*
Spiro Compounds / pharmacology
Structure-Activity Relationship

Substances

MCHR1 protein, human
Piperidines
Receptors, Somatostatin
Spiro Compounds