Identification of 4-amino-2-cyclohexylaminoquinazolines as metabolically stable melanin-concentrating hormone receptor 1 antagonists

…, M Nishiguchi, T Funakoshi, S Chaki, Y Nagase…

Index: Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Nagase, Yasuko; Iida, Izumi; Yamaguchi, Jun-ichi; Semple, Graeme; Tran, Thuy-Anh; Sekiguchi, Yoshinori Bioorganic and Medicinal Chemistry, 2006 , vol. 14, # 10 p. 3307 - 3319

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Citation Number: 31

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 ...