Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists.
Recently sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Replacing the sulfonamide functionality and reversing the original carboxamide bond led to the discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB(2) agonists. Selective CB(2) agonist 31 (K(i)=2.7; CB(1)/CB(2)=190) displayed robust activity in a rodent model of postoperative pain.
Worm
Karin
K
Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. kworm@adolor.com
Weaver
Damian G
DG
Green
Rosalyn C
RC
Saeui
Christopher T
CT
Dulay
Doreen-Marie S
DM
Barker
William M
WM
Cassel
Joel A
JA
Stabley
Gabriel J
GJ
DeHaven
Robert N
RN
LaBuda
Christopher J
CJ
Koblish
Michael
M
Brogdon
Bernice L
BL
Smith
Steven A
SA
Dolle
Roland E
RE
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D055808:Drug Discovery; D006801:Humans; D010149:Postoperative Pain / Q000188:drug therapy; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014162:Transfection
D000893:Anti-Inflammatory Agents; D001549:Benzamides; D043885:Receptor, Cannabinoid, CB2