title: Discovery of non-peptidergic MrgX1 and MrgX2 receptor agonists and exploration of an initial SAR using solid-phase synthesis.
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.
authors.affiliation: ACADIA Pharmaceuticals AB, Medeon Science Park, S-205 12 Malmö, Sweden.
authors.forename: Leila
authors.initials: L
authors.lastname: Malik
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Kelly
authors.forename: Jian-Nong
authors.initials: JN
authors.lastname: Ma
authors.forename: Erika A
authors.initials: EA
authors.lastname: Currier
authors.forename: Ethan S
authors.initials: ES
authors.lastname: Burstein
authors.forename: Roger
authors.initials: R
authors.lastname: Olsson
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D008253:Macaca mulatta; D008956:Models, Chemical; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry*; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; C480039:MRGPRX2 protein, human; D009419:Nerve Tissue Proteins; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C510803:mas-related gene-X1 receptor, human; C054598:corticostatin