title: Expansion of SAR studies on triaryl bis sulfone cannabinoid CB2 receptor ligands.
abstract: We report further expansion of the structure activity relationship (SAR) on the triaryl bis sulfone class of compounds (I), which are potent CB(2) receptor ligands with excellent selectivity over the CB(1) receptor. This study was extended to B ring changes, followed by simultaneous optimization of the A-, B-, and C-rings. Compound 42 has excellent CB(2) potency, selectivity and rat exposure.
authors.affiliation: Department of Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. ling.tong@spcorp.com
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.forename: B B
authors.initials: BB
authors.lastname: Shankar
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Razia
authors.initials: R
authors.lastname: Rizvi
authors.forename: Joseph
authors.initials: J
authors.lastname: Kelly
authors.forename: Eric
authors.initials: E
authors.lastname: Gilbert
authors.forename: Chunli
authors.initials: C
authors.lastname: Huang
authors.forename: De-Yi
authors.initials: DY
authors.lastname: Yang
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kozlowski
authors.forename: N-Y
authors.initials: NY
authors.lastname: Shih
authors.forename: W
authors.initials: W
authors.lastname: Gonsiorek
authors.forename: R William
authors.initials: RW
authors.lastname: Hipkin
authors.forename: Asra
authors.initials: A
authors.lastname: Malikzay
authors.forename: Charles A
authors.initials: CA
authors.lastname: Lunn
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lundell
mesh_terms: D000818:Animals; D008024:Ligands; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D013450:Sulfones