Structure–activity relationships of neuropeptide Y Y1 receptor antagonists related to BIBP 3226

Analogues of BIBP 3226, (R)-Nα-diphenylacetyl-N-(4-hydroxybenzyl)argininamide, were synthesized and investigated for Y1 antagonism (Ca2+-assay, HEL cells) and binding on Y1, Y2 and Y5 receptors. Replacing the benzylamino by a tetrahydrobenzazepinyl group preserves most of the Y1 activity. Combination with a NG-phenylpropyl arginine and a Nα-p-biphenylylacetyl moiety shifted the NPY receptor selectivity towards Y5.