title: Discovery of piperidine carboxamide TRPV1 antagonists.
abstract: A series of piperidine carboxamides were developed as potent antagonists of the transient receptor potential vanilloid-1 (TRPV1), an emerging target for the treatment of pain. A focused library of polar head groups led to the identification of a benzoxazinone amide that afforded good potency in cell-based assays. Synthesis and a QSAR model will be presented.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, Spring House, PA 19477, USA.
authors.forename: Wing S
authors.initials: WS
authors.lastname: Cheung
authors.forename: Raul R
authors.initials: RR
authors.lastname: Calvo
authors.forename: Brett A
authors.initials: BA
authors.lastname: Tounge
authors.forename: Sui-Po
authors.initials: SP
authors.lastname: Zhang
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Stone
authors.forename: Michael R
authors.initials: MR
authors.lastname: Brandt
authors.forename: Tasha
authors.initials: T
authors.lastname: Hutchinson
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Flores
authors.forename: Mark R
authors.initials: MR
authors.lastname: Player
mesh_terms: D000577:Amides / Q000737:chemistry*; D048588:Benzoxazines / Q000737:chemistry / Q000494:pharmacology*; D002211:Capsaicin / Q000737:chemistry; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D048588:Benzoxazines; D002352:Carrier Proteins; D010880:Piperidines; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002211:Capsaicin