title: Toward Labeled Argininamide-Type NPY Y1 Receptor Antagonists: Identification of a Favorable Propionylation Site in BIBO3304.
abstract: 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.
authors.affiliation: Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Keller
authors.affiliation: Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Schindler
authors.affiliation: Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Bernhardt
authors.affiliation: Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Buschauer
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D016466:CHO Cells; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D011422:Propionates / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011869:Radioligand Assay; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D008024:Ligands; D011422:Propionates; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C069339:argininamide; D001120:Arginine; C117416:BIBO 3304
keywords: Acylguanidine; Argininamide; BIBO3304; NPY Y1 receptor antagonist; Neuropeptide Y