Optimization of triaryl bis-sulfones as cannabinoid-2 receptor ligands.
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.
Lavey
Brian J
BJ
Department of Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. brian.lavey@spcorp.com <brian.lavey@spcorp.com>
Kozlowski
Joseph A
JA
Shankar
Bandarpalle B
BB
Spitler
James M
JM
Zhou
Guowei
G
Yang
De-Yi
DY
Shu
Youheng
Y
Wong
Michael K C
MK
Wong
Shing-Chun
SC
Shih
Neng-Yang
NY
Wu
Jie
J
McCombie
Stuart W
SW
Rizvi
Razia
R
Wolin
Ronald L
RL
Lunn
Charles A
CA
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*
D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D011955:Receptors, Drug; D013450:Sulfones; D012964:Sodium