1,3-Disubstituted benzazepines as neuropeptide Y Y1 receptor antagonists.
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)-methyl ureido)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (9: IC50 = 1.6 microM). Chemical modifications of 9 gave a potent NPY Y1 antagonist 3-(N-(4-hydroxyphenyl)-N'-methylguanidino)-1-N-(3-(N'-(tert-butoxy carbonyl)amino)benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (14c: IC5(0=43 nM), which had no affinity for NPY Y2 and Y5 receptors.
Murakami
Y
Y
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Hagishita
S
S
Okada
T
T
Kii
M
M
Hashizume
H
H
Yagami
T
T
Fujimoto
M
M
D001552:Benzazepines / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D009682:Magnetic Resonance Spectroscopy; D011869:Radioligand Assay; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D001552:Benzazepines; D017476:Receptors, Neuropeptide Y