Discovery of imidazo[1,2-a]pyridines as potent MCH1R antagonists

Hiroyuki Kishino; Minoru Moriya; Shunji Sakuraba; Toshihiro Sakamoto; Hidekazu Takahashi; Takao Suzuki; Ryuichi Moriya; Masahiko Ito; Hisashi Iwaasa; Norihiro Takenaga; Akane Ishihara; Akio Kanatani; Nagaaki Sato; Takehiro Fukami

doi:10.1016/j.bmcl.2009.06.101

Discovery of imidazo[1,2-a]pyridines as potent MCH1R antagonists

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4589-93. doi: 10.1016/j.bmcl.2009.06.101. Epub 2009 Jul 4.

Authors

Hiroyuki Kishino¹, Minoru Moriya, Shunji Sakuraba, Toshihiro Sakamoto, Hidekazu Takahashi, Takao Suzuki, Ryuichi Moriya, Masahiko Ito, Hisashi Iwaasa, Norihiro Takenaga, Akane Ishihara, Akio Kanatani, Nagaaki Sato, Takehiro Fukami

Affiliation

¹ Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co, Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan.

PMID: 19615899
DOI: 10.1016/j.bmcl.2009.06.101

Abstract

A series of imidazo[1,2-a]pyridine derivatives was identified and evaluated for MCH1R binding and antagonistic activity. Introduction of a methyl substituent at the 3-position of imidazo[1,2-a]pyridine provided compounds with a significant improvement in MCH1R affinity. Representative compounds in this series exhibited good potency and brain exposure in rats.

MeSH terms

Animals
Anti-Obesity Agents / chemical synthesis
Anti-Obesity Agents / chemistry*
Anti-Obesity Agents / pharmacology
CHO Cells
Cricetinae
Cricetulus
Drug Discovery
Humans
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacology
Rats
Receptors, Somatostatin / antagonists & inhibitors*
Receptors, Somatostatin / metabolism
Structure-Activity Relationship

Substances

Anti-Obesity Agents
MCHR1 protein, human
Pyridines
Receptors, Somatostatin