title: 7-Hydroxynaphthalen-1-yl-urea and -amide antagonists of human vanilloid receptor 1.
abstract: A series of structurally simple 7-hydroxynaphthalenyl ureas and amides were discovered to be potent ligands of human vanilloid receptor 1 (VR1). 1-(7-Hydroxynaphthalen-1-yl)-3-(4-trifluoromethylbenzyl)urea 5f exhibited nanomolar binding affinity (K(i)=1.0nM) and upon capsaicin challenge, behaved as a potent functional antagonist (IC(50)=4nM). The synthesis and structure-activity relationships (SARs) for the series are described.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, Spring House, PA 19477, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: McDonnell
authors.forename: Sui Po
authors.initials: SP
authors.lastname: Zhang
authors.forename: Nadia
authors.initials: N
authors.lastname: Nasser
authors.forename: Adrienne E
authors.initials: AE
authors.lastname: Dubin
authors.forename: Scott L
authors.initials: SL
authors.lastname: Dax
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009284:Naphthols / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D050916:TRPV Cation Channels; D014508:Urea / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000577:Amides; D009284:Naphthols; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D014508:Urea