521074-25-9Relevant articles and documents
Melanin-concentrating hormone receptor 1 antagonists. Synthesis and structure-activity relationships of novel 3-(aminomethyl)quinolines
Kamata, Makoto,Yamashita, Toshiro,Imaeda, Toshihiro,Tanaka, Toshio,Masada, Shinichi,Kamaura, Masahiro,Kasai, Shizuo,Hara, Ryoma,Sasaki, Shigekazu,Takekawa, Shiro,Asami, Asano,Kaisho, Tomoko,Suzuki, Nobuhiro,Ashina, Shuntaro,Ogino, Hitomi,Nakano, Yoshihide,Nagisa, Yasutaka,Kato, Koki,Kato, Kaneyoshi,Ishihara, Yuji
, p. 2353 - 2366 (2012/05/05)
It was found that 3-(aminomethyl)quinoline derivatives showed high binding affinities for melanin-concentrating hormone receptor 1 (MCHR1) with reduced affinity for serotonin receptor 2c (5-HT2c) when the dihydronaphthalene nucleus of compound 1 (human MCHR1, IC50 = 1.9 nM; human 5-HT2c receptor, IC50 = 0.53 nM) was replaced by other bicyclic core scaffolds. Among the synthesized compounds, 8-methylquinoline derivative 5v especially showed high binding affinity (IC50 = 0.54 nM), potent in vitro antagonistic activity (IC50 = 2.8 nM) for MCHR1, and negligible affinity for 5-HT2c receptor (IC50 > 1000 nM). Oral administration of 5v significantly and dose-dependently suppressed nocturnal food intake in diet-induced obese rats and did not affect food intake in MCHR1-deficient mice. These results and rat pharmacokinetic study findings suggested that compound 5v is a highly potent, orally bioavailable, and centrally acting nonpeptide MCHR1 antagonist.
