Author/Authors :
Kosuke Kanuma، نويسنده , , Katsunori Omodera، نويسنده , , Mariko Nishiguchi، نويسنده , , Takeo Funakoshi، نويسنده , , Shigeyuki Chaki، نويسنده , , Yasuko Nagase، نويسنده , , Izumi Iida، نويسنده , , Jun-ichi Yamaguchi، نويسنده , , Graeme Semple، نويسنده , , Thuy-Anh Tran، نويسنده , , Yoshinori Sekiguchi، نويسنده ,
Abstract :
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.
