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

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1729-32. doi: 10.1016/j.bmcl.2009.01.085. Epub 2009 Jan 30.


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.

MeSH terms

  • Animals
  • Benzimidazoles / chemistry
  • Cattle
  • Chemistry, Pharmaceutical / methods*
  • Combinatorial Chemistry Techniques
  • Drug Design
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Macaca mulatta
  • Models, Chemical
  • Nerve Tissue Proteins / agonists*
  • Nerve Tissue Proteins / chemistry*
  • Peptides / chemistry
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, Neuropeptide / agonists*
  • Receptors, Neuropeptide / chemistry*
  • Structure-Activity Relationship


  • Benzimidazoles
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • MRGPRX2 protein, human
  • Nerve Tissue Proteins
  • Peptides
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • mas-related gene-X1 receptor, human
  • corticostatin