title: Optimization of triaryl bis-sulfones as cannabinoid-2 receptor ligands.
abstract: Structure-activity relationship on our recently reported triaryl bis-sulfone class of cannabinoid-2 (CB2) receptor selective inverse agonists was explored. Modifications to the methane sulfonamide, substitutions to B and C phenyl rings, and replacements of the C-ring were investigated. A compound with excellent CB2 activity, selectivity for CB2 over CB1, and in vivo plasma levels was identified.
authors.affiliation: Department of Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. brian.lavey@spcorp.com <brian.lavey@spcorp.com>
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lavey
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kozlowski
authors.forename: Bandarpalle B
authors.initials: BB
authors.lastname: Shankar
authors.forename: James M
authors.initials: JM
authors.lastname: Spitler
authors.forename: Guowei
authors.initials: G
authors.lastname: Zhou
authors.forename: De-Yi
authors.initials: DY
authors.lastname: Yang
authors.forename: Youheng
authors.initials: Y
authors.lastname: Shu
authors.forename: Michael K C
authors.initials: MK
authors.lastname: Wong
authors.forename: Shing-Chun
authors.initials: SC
authors.lastname: Wong
authors.forename: Neng-Yang
authors.initials: NY
authors.lastname: Shih
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Stuart W
authors.initials: SW
authors.lastname: McCombie
authors.forename: Razia
authors.initials: R
authors.lastname: Rizvi
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Wolin
authors.forename: Charles A
authors.initials: CA
authors.lastname: Lunn
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D011485:Protein Binding; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry*; D011955:Receptors, Drug; D012964:Sodium / Q000737:chemistry; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry*
chemical_list: D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D011955:Receptors, Drug; D013450:Sulfones; D012964:Sodium