Discovery of piperidine carboxamide TRPV1 antagonists.
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.
Cheung
Wing S
WS
Johnson & Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, Spring House, PA 19477, USA.
Calvo
Raul R
RR
Tounge
Brett A
BA
Zhang
Sui-Po
SP
Stone
Dennis R
DR
Brandt
Michael R
MR
Hutchinson
Tasha
T
Flores
Christopher M
CM
Player
Mark R
MR
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*
D000577:Amides; D048588:Benzoxazines; D002352:Carrier Proteins; D010880:Piperidines; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002211:Capsaicin