Toward Labeled Argininamide-Type NPY Y1 Receptor Antagonists: Identification of a Favorable Propionylation Site in BIBO3304.

Aiming at molecular tools for the neuropeptide Y Y1 receptor (Y1 R), three types of derivatives of the argininamide-type Y1 R antagonist BIBO3304 were prepared by (i) propionylation at the guanidine group (3), (ii) substitution at the urea moiety with a propionamidobutyl residue (4), and (iii) replacement of ureidomethyl by a propionylaminomethyl group (5). With Ki and Kb values in the range of 1.5-4.3 nM, determined in binding and functional assays, and high selectivity for the Y1 R over the Y2 R, Y4 R, and Y5 R, compounds 4 and 5 were identified as promising candidates for radiolabeling by [(3) H]propionylation according to established protocols.