Abstract
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.
MeSH terms
-
Administration, Oral
-
Aminopyridines / chemical synthesis
-
Aminopyridines / chemistry*
-
Aminopyridines / pharmacology
-
Animals
-
Dogs
-
Humans
-
Male
-
Microsomes, Liver
-
Morpholines / chemical synthesis
-
Morpholines / chemistry*
-
Morpholines / pharmacology
-
Pain / drug therapy
-
Protein Binding
-
Pyridines / chemical synthesis
-
Pyridines / chemistry*
-
Pyridines / pharmacokinetics
-
Rats
-
Rats, Sprague-Dawley
-
Receptor, Cannabinoid, CB1 / agonists
-
Receptor, Cannabinoid, CB1 / metabolism
-
Receptor, Cannabinoid, CB2 / agonists*
-
Receptor, Cannabinoid, CB2 / metabolism
-
Structure-Activity Relationship
Substances
-
2,2-dimethyl-N-(5-methyl-4-(morpholinomethyl)pyridin-2-yl)butanamide
-
Aminopyridines
-
Morpholines
-
Pyridines
-
Receptor, Cannabinoid, CB1
-
Receptor, Cannabinoid, CB2