Structure-activity relationship of a novel class of naphthyl amide KATP channel openers

Bioorg Med Chem Lett. 2003 May 19;13(10):1741-4. doi: 10.1016/s0960-894x(03)00205-1.

Abstract

We have discovered a novel series of N-[2-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-naphthalen-1-yl] amides that are potent openers of K(ATP) channels and investigated structure-activity relationships (SAR) around the 1,2-disubstituted naphthyl core. A-151892, a prototype compound of this series, was found to be a potent and efficacious potassium channel opener in vitro in transfected Kir6.2/SUR2B cells and pig bladder strips. Additionally, A-151892 was found to selectively inhibit unstable bladder contractions in vivo in an obstructed rat model of myogenic bladder function

MeSH terms

  • ATP-Binding Cassette Transporters / agonists
  • ATP-Binding Cassette Transporters / genetics
  • Amides / administration & dosage
  • Amides / chemical synthesis*
  • Amides / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Cell Line
  • Fluorescent Dyes
  • Humans
  • Hypertrophy / drug therapy
  • Male
  • Membrane Potentials / drug effects
  • Muscle Contraction / drug effects
  • Naphthalenes / administration & dosage
  • Naphthalenes / chemical synthesis
  • Naphthalenes / pharmacology
  • Potassium Channels / agonists*
  • Potassium Channels / genetics
  • Potassium Channels, Inwardly Rectifying / agonists
  • Potassium Channels, Inwardly Rectifying / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / agonists
  • Receptors, Drug / genetics
  • Structure-Activity Relationship
  • Sulfonylurea Receptors
  • Swine
  • Transfection
  • Urinary Bladder / pathology

Substances

  • ATP-Binding Cassette Transporters
  • Amides
  • Fluorescent Dyes
  • Naphthalenes
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors