title: Spiro-piperidine azetidinones as potent TRPV1 antagonists.
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.
authors.affiliation: Chemical Research Department, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. dong.xiao@spcorp.com
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
authors.forename: Anandan
authors.initials: A
authors.lastname: Palani
authors.forename: Robert
authors.initials: R
authors.lastname: Aslanian
authors.forename: Brian A
authors.initials: BA
authors.lastname: McKittrick
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McPhail
authors.forename: Craig C
authors.initials: CC
authors.lastname: Correll
authors.forename: P Tara
authors.initials: PT
authors.lastname: Phelps
authors.forename: John C
authors.initials: JC
authors.lastname: Anthes
authors.forename: Diane
authors.initials: D
authors.lastname: Rindgen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001384:Azetidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D051381:Rats; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: C116379:2-azetidinone; D001384:Azetidines; D013141:Spiro Compounds; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human