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N(omega)-carbamoylation of the argininamide moiety: an avenue to insurmountable NPY Y1 receptor antagonists and a radiolabeled selective high affinity molecular tool ([3H]UR-MK299) with extended residence time

Keller, Max ; Weiss, Stefan ; Hutzler, Christoph ; Kuhn, Kilian K. ; Mollereau, Catherine ; Dukorn, Stefanie ; Schindler, Lisa ; Bernhardt, Günther ; König, Burkhard ; Buschauer, Armin


Analogs of the argininamide-type NPY Y1 receptor (Y1R) antagonist BIBP3226, bearing carbamoyl moieties at the guanidine group, revealed subnanomolar Ki values and caused depression of the maximal response to NPY (calcium assay) by up to 90% in a concentration- and time-dependent manner, suggesting insurmountable antagonism. To gain insight into the mechanism of binding of the synthesized ...


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