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Argininamide-type neuropeptide Y Y1 receptor antagonists: the nature of Nω-carbamoyl substituents determines Y1R binding mode and affinity

Buschmann, Jonas ; Seiler, Theresa ; Bernhardt, Günther ; Keller, Max ; Wifling, David


The recently resolved crystal structure of the neuropeptide Y Y-1 receptor (Y1R), co-crystallized with the high-affinity (pK(i): 10.11), argininamide-type Y1R antagonist UR-MK299 (2), revealed that the N-omega-carbamoyl substituent (van der Waals volume: 139 angstrom(3)) is deeply buried in the receptor, occupying a hydrophobic pocket. We synthesized and characterized a series of argininamides, ...


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