Guanidine-acylguanidine bioisosteric approach in the design of radioligands: synthesis of a tritium-labeled N(G)-propionylargininamide ([3H]-UR-MK114) as a highly potent and selective neuropeptide Y Y1 receptor antagonist.
Synthesis and characterization of (R)-N(alpha)-(2,2-diphenylacetyl)-N-(4-hydroxybenzyl)-N(omega)-([2,3-(3)H]-propanoyl)argininamide ([(3)H]-UR-MK114), an easily accessible tritium-labeled NPY Y(1) receptor (Y(1)R) antagonist (K(B): 0.8 nM, calcium assay, HEL cells) derived from the (R)-argininamide BIBP 3226, is reported. The radioligand binds with high affinity (K(D), saturation: 1.2 nM, kinetic experiments: 1.1 nM, SK-N-MC cells) and selectivity for Y(1)R over Y(2), Y(4), and Y(5) receptors. The title compound is a useful pharmacological tool for the determination of Y(1)R ligand affinities, quantification of Y(1)R binding sites, and autoradiography.
Keller
Max
M
Department of Pharmaceutical/Medicinal Chemistry II, Faculty of Chemistry and Pharmacy, University of Regensburg, D-93053 Regensburg, Germany.
Pop
Nathalie
N
Hutzler
Christoph
C
Beck-Sickinger
Annette G
AG
Bernhardt
Günther
G
Buschauer
Armin
A
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D016466:CHO Cells; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D019791:Guanidine / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014316:Tritium / Q000737:chemistry*
C534492:Nalpha-(2,2-diphenylacetyl)-N-(4-hydroxybenzyl)-Nomega-propanoylargininamide; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D014316:Tritium; C069339:argininamide; D001120:Arginine; D019791:Guanidine