Expansion of SAR studies on triaryl bis sulfone cannabinoid CB2 receptor ligands.
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.
Tong
Ling
L
Department of Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. ling.tong@spcorp.com
Shankar
B B
BB
Chen
Lei
L
Rizvi
Razia
R
Kelly
Joseph
J
Gilbert
Eric
E
Huang
Chunli
C
Yang
De-Yi
DY
Kozlowski
Joseph A
JA
Shih
N-Y
NY
Gonsiorek
W
W
Hipkin
R William
RW
Malikzay
Asra
A
Lunn
Charles A
CA
Lundell
Daniel J
DJ
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*
D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D013450:Sulfones