1,3-Disubstituted benzazepines as neuropeptide Y Y1 receptor antagonists Original Research Article

A novel class of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Through a blind screening we found the compound 1-N-(3-(N′-(tert-butoxycarbonyl)amino)benzyl)-7-methoxy-(3-(3)-methylureido)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (: IC50=1.6 μM). Chemical modifications of gave a potent NPY Y1 antagonist 3-(N-(4-hydroxyphenyl)-N′-methylguanidino)-1-N-(3-(N′-(tert-butoxycarbonyl)amino)benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (: IC50=43 nM), which had no affinity for NPY Y2 and Y5 receptors.