title: Naphthol derivatives as TRPV1 inhibitors for the treatment of urinary incontinence.
abstract: We have identified naphthol derivatives as inhibitors of the vanilloid receptor TRPV1 by high throughput screening. The initial lead showed high clearance in rats and has been optimized by enhancing the acidity of the phenol group. Compound 6b has reduced clearance, improved potency and is active in rat cystometry models of urinary incontinence after intravenous administration.
authors.affiliation: Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto 619-0216, Japan. Klaus.Urbahns@merck.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Urbahns
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yura
authors.forename: Muneto
authors.initials: M
authors.lastname: Mogi
authors.forename: Masaomi
authors.initials: M
authors.lastname: Tajimi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujishima
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masuda
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Yoshida
authors.forename: Toshiya
authors.initials: T
authors.lastname: Moriwaki
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Lowinger
authors.forename: Heinrich
authors.initials: H
authors.lastname: Meier
authors.forename: Fiona
authors.initials: F
authors.lastname: Chan
authors.forename: David
authors.initials: D
authors.lastname: Madge
authors.forename: Jang B
authors.initials: JB
authors.lastname: Gupta
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009284:Naphthols / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D010288:Parenteral Nutrition; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D014549:Urinary Incontinence / Q000188:drug therapy*
chemical_list: D009284:Naphthols; D050916:TRPV Cation Channels; C494484:TRPV1 receptor