Discovery of non-peptidergic MrgX1 and MrgX2 receptor agonists and exploration of an initial SAR using solid-phase synthesis

Research output: Contribution to journalArticle

Abstract

A class of small molecules displaying comparable activities with peptide ligands BAM22 and corticostatin-14 at both the human and rhesus monkey MrgX1 and MrgX2 receptors, respectively, was discovered. A comparative study to compare solid-phase and solution-phase chemistries for the efficient synthesis of the active class, tetracyclic benzimidazoles, was undertaken. The solid-phase chemistry was found to be superior both for the synthesis of analogs and for the synthesis of gram quantities.

Details

Authors
  • Leila Malik
  • Nicholas M. Kelly
  • Jian Nong Ma
  • Erika A. Currier
  • Ethan S. Burstein
  • Roger Olsson
External organisations
  • ACADIA Pharmaceuticals AB
  • ACADIA Pharmaceuticals Inc.
Research areas and keywords

Keywords

  • Agonist, Mas related, MrgX1, MrgX2, Nociception, Non-peptidergic, R-SAT, Sensory-neuron specific receptors, Small molecule, SNSR, Solid-phase
Original languageEnglish
Pages (from-to)1729-1732
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number6
Publication statusPublished - 2009 Mar 15
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes