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

Abstract

Synthesis and characterization of (R)-N(alpha)-(2,2-diphenylacetyl)-N-(4-hydroxybenzyl)-N(omega)-([2,3-3H2]-propanoyl)argininamide ([3H]-UR-MK114), an easily accessible tritium-labeled NPY Y1 receptor (Y1R) antagonist (KB: 0.8 nM, calcium assay, HEL cells) derived from the (R)-argininamide BIBP 3226, is reported. The radioligand binds with high affinity (KD, saturation: 1.2 nM, kinetic experiments: 1.1 nM, SK-N-MC cells) and selectivity for Y1R over Y2, Y4 and Y5 receptors. The title compound is a useful pharmacological tool for the determination of Y1R ligand affinities, quantification of Y1R binding sites and autoradiography.