Nitric oxide donor beta2-agonists: furoxan derivatives containing the fenoterol moiety and related furazans

J Med Chem. 2007 Oct 4;50(20):5003-11. doi: 10.1021/jm0704595. Epub 2007 Sep 11.

Abstract

The structure of fenoterol, a beta2-adrenoceptor agonist used in therapy, has been joined with furoxan NO-donor moieties to give new NO-donor beta2-agonists. The furazan analogues, devoid of the property to release NO, were also synthesized for comparison. All the compounds retained beta2-agonistic activity at micromolar or submicromolar concentration when tested on guinea pig tracheal rings precontracted with carbachol. Among the furoxan derivatives, the NO contribution to trachea relaxation was evident with product 15b at micromolar concentrations. All the new NO-donor hybrids were able to dilate rat aortic strips precontracted with phenylephrine. Both furoxan and furazan derivatives displayed antioxidant activity greater than that of fenoterol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists*
  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Aorta / drug effects
  • Aorta / physiology
  • Fenoterol / analogs & derivatives*
  • Fenoterol / chemical synthesis*
  • Fenoterol / chemistry
  • Fenoterol / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Microsomes, Liver / metabolism
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / chemistry
  • Nitric Oxide Donors / chemical synthesis*
  • Nitric Oxide Donors / chemistry
  • Nitric Oxide Donors / pharmacology
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology
  • Rats
  • Rats, Wistar
  • Stereoisomerism
  • Structure-Activity Relationship
  • Trachea / drug effects
  • Trachea / physiology
  • Vasodilator Agents / chemical synthesis
  • Vasodilator Agents / chemistry
  • Vasodilator Agents / pharmacology

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Antioxidants
  • Nitric Oxide Donors
  • Oxadiazoles
  • Vasodilator Agents
  • furoxans
  • Fenoterol
  • Nitric Oxide