Bioorganic & Medicinal Chemistry Letters 2009-07-01

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

Index: Bioorg. Med. Chem. Lett. 19(13) , 3568-72, (2009)

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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.