509142-46-5Relevant academic research and scientific papers
Lead optimization of 4-(dimethylamino)quinazolines, potent and selective antagonists for the melanin-concentrating hormone receptor 1
Kanuma, Kosuke,Omodera, Katsunori,Nishiguchi, Mariko,Funakoshi, Takeo,Chaki, Shigeyuki,Semple, Graeme,Tran, Thuy-Anh,Kramer, Bryan,Hsu, Debbie,Casper, Martin,Thomsen, Bill,Sekiguchi, Yoshinori
, p. 3853 - 3856 (2005)
The optimization of a series of 4-(dimethylamino)quinazoline antagonists of the melanin-concentrating hormone receptor 1 (MCH-R1) is described. The combination of the elaboration of both the linker portion and the terminal phenyl ring provided N-(cis-4-{[4-(dimethylamino)quinazolin-2-yl]amino} cyclohexyl)-3,4-difluorobenzamide hydrochloride 28 (ATC0175), which showed excellent antagonist activity at the MCH-R1 (IC50 = 3.4 nM) as well as good selectivity over the Y5 and the α2A receptors.
Identification of 4-amino-2-cyclohexylaminoquinazolines as metabolically stable melanin-concentrating hormone receptor 1 antagonists
Kanuma, Kosuke,Omodera, Katsunori,Nishiguchi, Mariko,Funakoshi, Takeo,Chaki, Shigeyuki,Nagase, Yasuko,Iida, Izumi,Yamaguchi, Jun-ichi,Semple, Graeme,Tran, Thuy-Anh,Sekiguchi, Yoshinori
, p. 3307 - 3319 (2007/10/03)
The optimization of the distance between two key pharmacophore features within our first hit compounds 1a and 2a led to the identification of a new class of potent non-peptidic antagonists for the MCH-R1, based around 4-amino-2-cyclohexylaminoquinazolines. In particular, ATC0065 (2c), N2-[cis-4-({2-[4-Bromo-2-(trifluoromethoxy)phenyl]ethyl}amino)cyclohexyl]-N4,N4-dimethylquinazoline-2,4-diamine dihydrochloride, bound with high affinity to the MCH-R1 (IC50 value of 16 nM) and showed good metabolic stability in liver microsomes from human and rat.
