New potential uroselective NO-donor alpha1-antagonists

J Med Chem. 2003 Aug 14;46(17):3762-5. doi: 10.1021/jm030825u.

Abstract

A recent uroselective alpha(1)-adrenoceptor antagonist, REC15/2739, has been joined with nitrooxy and furoxan NO-donor moieties to give new NO-donor alpha(1)-antagonists. All the compounds studied proved to be potent and selective ligands of human cloned alpha(1a)-receptor subtype. Derivatives 6 and 7 were able to relax the prostatic portion of rat vas deferens contracted by (-)-noradrenaline because of both their alpha(1A)-antagonist and their NO-donor properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / chemical synthesis
  • Adrenergic alpha-Antagonists / chemistry
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Chromones / chemical synthesis*
  • Chromones / chemistry
  • Chromones / pharmacology
  • Cricetinae
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Male
  • Muscle Relaxation
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Nitric Oxide Donors / chemical synthesis*
  • Nitric Oxide Donors / chemistry
  • Nitric Oxide Donors / pharmacology
  • Nitrous Acid / chemistry*
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology
  • Radioligand Assay
  • Rats
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT1
  • Vas Deferens / drug effects
  • Vas Deferens / physiology

Substances

  • ADRA1A protein, human
  • Adra1a protein, rat
  • Adrenergic alpha-Antagonists
  • Chromones
  • Nitric Oxide Donors
  • Oxadiazoles
  • Rec 15-2739
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • furoxans
  • Nitrous Acid