title: Sulfamoyl benzamides as novel CB2 cannabinoid receptor ligands.
abstract: Sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Starting from a screening hit 8 that had modest affinity for the cannabinoid CB(2) receptor, a parallel synthesis approach and initial SAR are described, leading to compound 27 with 120-fold functional selectivity for the CB(2) receptor. This compound produced robust antiallodynic activity in rodent models of postoperative pain and neuropathic pain without traditional cannabinergic side effects.
authors.affiliation: Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA, USA. kworm@adolor.com
authors.forename: Karin
authors.initials: K
authors.lastname: Worm
authors.forename: Q Jean
authors.initials: QJ
authors.lastname: Zhou
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Saeui
authors.forename: Rosalyn C
authors.initials: RC
authors.lastname: Green
authors.forename: Joel A
authors.initials: JA
authors.lastname: Cassel
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Stabley
authors.forename: Robert N
authors.initials: RN
authors.lastname: DeHaven
authors.forename: Nathalie
authors.initials: N
authors.lastname: Conway-James
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: LaBuda
authors.forename: Michael
authors.initials: M
authors.lastname: Koblish
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Little
authors.forename: Roland E
authors.initials: RE
authors.lastname: Dolle
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D051379:Mice; D023421:Models, Animal; D008956:Models, Chemical; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides