N-isoquinolin-5-yl-N'-aralkyl-urea and -amide antagonists of human vanilloid receptor 1.
Starting from a low micromolar agonist lead identified by high-throughput screening, series of N-isoquinolin-5-yl-N'-aralkyl ureas and analogous amides were developed as potent antagonists of human vanilloid receptor 1 (VR1). The synthesis and structure-activity relationships (SAR) of the series are described.
Jetter
Michele C
MC
Johnson & Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, Spring House, PA 19477, USA.
Youngman
Mark A
MA
McNally
James J
JJ
Zhang
Sui-Po
SP
Dubin
Adrienne E
AE
Nasser
Nadia
N
Dax
Scott L
SL
D000577:Amides / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000378:metabolism; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050916:TRPV Cation Channels; D014508:Urea / Q000737:chemistry* / Q000378:metabolism
D000577:Amides; D007546:Isoquinolines; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D014508:Urea