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

Arch Pharm (Weinheim). 2015 Jun;348(6):390-8. doi: 10.1002/ardp.201400427. Epub 2015 Apr 17.

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.

Keywords: Acylguanidine; Argininamide; BIBO3304; NPY Y1 receptor antagonist; Neuropeptide Y.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / chemical synthesis
  • Arginine / metabolism
  • Arginine / pharmacology
  • Binding Sites
  • Binding, Competitive
  • CHO Cells
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Ligands
  • Molecular Structure
  • Propionates / chemical synthesis*
  • Propionates / metabolism
  • Propionates / pharmacology*
  • Protein Binding
  • Radioligand Assay
  • Receptors, Neuropeptide Y / antagonists & inhibitors*
  • Receptors, Neuropeptide Y / chemistry
  • Receptors, Neuropeptide Y / genetics
  • Receptors, Neuropeptide Y / metabolism
  • Structure-Activity Relationship
  • Transfection

Substances

  • Ligands
  • Propionates
  • Receptors, Neuropeptide Y
  • neuropeptide Y-Y1 receptor
  • argininamide
  • Arginine
  • BIBO 3304