Naphthol derivatives as TRPV1 inhibitors for the treatment of urinary incontinence

Klaus Urbahns; Takeshi Yura; Muneto Mogi; Masaomi Tajimi; Hiroshi Fujishima; Tsutomu Masuda; Nagahiro Yoshida; Toshiya Moriwaki; Timothy B Lowinger; Heinrich Meier; Fiona Chan; David Madge; Jang B Gupta

doi:10.1016/j.bmcl.2011.04.013

Naphthol derivatives as TRPV1 inhibitors for the treatment of urinary incontinence

Bioorg Med Chem Lett. 2011 Jun 1;21(11):3354-7. doi: 10.1016/j.bmcl.2011.04.013. Epub 2011 Apr 9.

Authors

Klaus Urbahns¹, Takeshi Yura, Muneto Mogi, Masaomi Tajimi, Hiroshi Fujishima, Tsutomu Masuda, Nagahiro Yoshida, Toshiya Moriwaki, Timothy B Lowinger, Heinrich Meier, Fiona Chan, David Madge, Jang B Gupta

Affiliation

¹ Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto 619-0216, Japan. Klaus.Urbahns@merck.de

PMID: 21531136
DOI: 10.1016/j.bmcl.2011.04.013

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.

MeSH terms

Animals
Disease Models, Animal
Female
Inhibitory Concentration 50
Molecular Structure
Naphthols / chemical synthesis
Naphthols / chemistry*
Naphthols / therapeutic use
Parenteral Nutrition
Rats
Structure-Activity Relationship
TRPV Cation Channels / antagonists & inhibitors*
Urinary Incontinence / drug therapy*

Substances

Naphthols
TRPV Cation Channels
TRPV1 receptor