Spiro-piperidine azetidinones as potent TRPV1 antagonists

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. (C) 2008 Elsevier Ltd. All rights reserved.