Toward Labeled Argininamide‐Type NPY Y 1 Receptor Antagonists: Identification of a Favorable Propionylation Site in BIBO3304

Aiming at molecular tools for the neuropeptide Y Y 1 receptor (Y 1 R), three types of derivatives of the argininamide‐type Y 1 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 K i and K b values in the range of 1.5–4.3 nM, determined in binding and functional assays, and high selectivity for the Y 1 R over the Y 2 R, Y 4 R, and Y 5 R, compounds 4 and 5 were identified as promising candidates for radiolabeling by [ 3 H]propionylation according to established protocols.