Identification of 2-aminobenzimidazoles as potent melanin-concentrating hormone 1-receptor (MCH1R) antagonists

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

doi:10.1016/j.bmcl.2009.04.147

Identification of 2-aminobenzimidazoles as potent melanin-concentrating hormone 1-receptor (MCH1R) antagonists

Bioorg Med Chem Lett. 2009 Jul 1;19(13):3568-72. doi: 10.1016/j.bmcl.2009.04.147. Epub 2009 May 5.

Authors

Minoru Moriya¹, Hiroyuki Kishino, Shunji Sakuraba, Toshihiro Sakamoto, Takuya Suga, Hidekazu Takahashi, Takao Suzuki, Masahiko Ito, Junko Ito, Ryuichi Moriya, Norihiro Takenaga, Hisashi Iwaasa, Akane Ishihara, Akio Kanatani, Takehiro Fukami

Affiliation

¹ Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo-3, Tsukuba, Ibaraki 300-2611, Japan. [email protected]

PMID: 19457661
DOI: 10.1016/j.bmcl.2009.04.147

Abstract

A series of 2-aminobenzimidazole-based MCH1R antagonists was identified by core replacement of the aminoquinoline lead 1. Subsequent modification of the 2- and 5-positions led to improvement in potency and intrinsic clearance. Compound 25 exhibited good plasma and brain exposure, and attenuated MCH induced food intake at 30mg/kg PO in rats.

MeSH terms

Animals
Anti-Obesity Agents / chemical synthesis
Anti-Obesity Agents / chemistry*
Anti-Obesity Agents / pharmacokinetics
Benzimidazoles / chemical synthesis
Benzimidazoles / chemistry*
Benzimidazoles / pharmacokinetics
Eating / drug effects
Rats
Rats, Sprague-Dawley
Receptors, Somatostatin / antagonists & inhibitors*
Receptors, Somatostatin / metabolism
Structure-Activity Relationship

Substances

Anti-Obesity Agents
Benzimidazoles
MCHR1 protein, rat
Receptors, Somatostatin
2-aminobenzimidazole