Novel pyridine derivatives as potent and selective CB2 cannabinoid receptor agonists.
Replacement of the phenyl ring in our previous (morpholinomethyl)aniline carboxamide cannabinoid receptor ligands with a pyridine ring led to the discovery of a novel chemical series of CB2 ligands. Compound 3, that is, 2,2-dimethyl-N-(5-methyl-4-(morpholinomethyl)pyridin-2-yl)butanamide was identified as a potent and selective CB2 agonist exhibiting in vivo efficacy after oral administration in a rat model of neuropathic pain.
Chu
Guo-Hua
GH
Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. ghchu@adolor.com
Saeui
Christopher T
CT
Worm
Karin
K
Weaver
Damian G
DG
Goodman
Allan J
AJ
Broadrup
Robert L
RL
Cassel
Joel A
JA
DeHaven
Robert N
RN
LaBuda
Christopher J
CJ
Koblish
Michael
M
Brogdon
Bernice
B
Smith
Steve
S
Le Bourdonnec
Bertrand
B
Dolle
Roland E
RE
D000284:Administration, Oral; D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D006801:Humans; D008297:Male; D008862:Microsomes, Liver; D009025:Morpholines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
C546014:2,2-dimethyl-N-(5-methyl-4-(morpholinomethyl)pyridin-2-yl)butanamide; D000631:Aminopyridines; D009025:Morpholines; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2