کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1357092 | 981199 | 2006 | 13 صفحه PDF | دانلود رایگان |
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.
Through an optimization of the distance between two key pharmacophore features, 4-amino-2-cyclohexylaminoquinazolines were identified as potent melanin-concentrating hormone receptor 1 (MCH-R1) antagonists, leading to the discovery of ATC0065.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 14, Issue 10, 15 May 2006, Pages 3307–3319