Discovery of imidazo[1,2-a]pyridines as potent MCH1R antagonists.
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.
Kishino
Hiroyuki
H
Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co, Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan.
Moriya
Minoru
M
Sakuraba
Shunji
S
Sakamoto
Toshihiro
T
Takahashi
Hidekazu
H
Suzuki
Takao
T
Moriya
Ryuichi
R
Ito
Masahiko
M
Iwaasa
Hisashi
H
Takenaga
Norihiro
N
Ishihara
Akane
A
Kanatani
Akio
A
Sato
Nagaaki
N
Fukami
Takehiro
T
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D055808:Drug Discovery; D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; C103263:MCHR1 protein, human; D011725:Pyridines; D017481:Receptors, Somatostatin