Sulfamoyl benzamides as novel CB2 cannabinoid receptor ligands.
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.
Worm
Karin
K
Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA, USA. kworm@adolor.com
Zhou
Q Jean
QJ
Saeui
Christopher T
CT
Green
Rosalyn C
RC
Cassel
Joel A
JA
Stabley
Gabriel J
GJ
DeHaven
Robert N
RN
Conway-James
Nathalie
N
LaBuda
Christopher J
CJ
Koblish
Michael
M
Little
Patrick J
PJ
Dolle
Roland E
RE
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*
D001549:Benzamides; D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides