Abstract
A series of spiro-piperidine azetidinone were synthesized and evaluated as potential TRPV1 antagonists. An important issue of plasma stability was investigated and resolved. Further focused SAR study lead to the discovery of a potent antagonist with good oral pharmacokinetic profile in rat.
MeSH terms
-
Administration, Oral
-
Animals
-
Azetidines / chemical synthesis*
-
Azetidines / pharmacokinetics*
-
Chemistry, Pharmaceutical / methods*
-
Drug Design
-
Hydrogen-Ion Concentration
-
Inhibitory Concentration 50
-
Models, Chemical
-
Rats
-
Spiro Compounds / chemical synthesis*
-
Spiro Compounds / pharmacology*
-
Stereoisomerism
-
Structure-Activity Relationship
-
TRPV Cation Channels / antagonists & inhibitors*
Substances
-
2-azetidinone
-
Azetidines
-
Spiro Compounds
-
TRPV Cation Channels
-
TRPV1 protein, human