New isoxazole derivatives provided with antihypertensive activity

Arzneimittelforschung. 1989 Jun;39(6):642-6. doi: 10.1002/chin.198948203.


A series of diazacycloalkane-quinazoline derivatives of isoxazoles were synthesized and tested in order to identify new potent and selective alpha 1-antagonists. A preliminary screening by using in vitro tests such as binding assay (3H-prazosin and 3H-rauwolscine displacement) and analysis of antagonistic activity in isolated rat aorta (norepinephrine-induced response) and in isolated rat vas deferens (clonidine-induced response) indicated that many of these compounds exhibited a good affinity and selectivity towards alpha 1-adrenergic receptors associated with potent pharmacological activity. In particular, a 3-bromo-5-isoxazolecarbonyl derivative, selected for further in vivo investigation, was provided with as high antihypertensive action as prazosin in spontaneously hypertensive rats (SHR) coupled to a shallow dose-response curve by oral route. Moreover, a higher ratio between oral antihypertensive doses in SHR and normotensive rats was found with respect to reference compound prazosin.

MeSH terms

  • Animals
  • Antihypertensive Agents* / chemical synthesis
  • Aorta, Thoracic / drug effects
  • Binding, Competitive / drug effects
  • Chemical Phenomena
  • Chemistry
  • Clonidine / pharmacology
  • In Vitro Techniques
  • Isoxazoles / chemical synthesis
  • Isoxazoles / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Norepinephrine / metabolism
  • Oxazoles / pharmacology*
  • Prazosin / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred Strains
  • Rats, Inbred WKY
  • Vas Deferens / drug effects
  • Yohimbine / metabolism


  • Antihypertensive Agents
  • Isoxazoles
  • Oxazoles
  • Yohimbine
  • Clonidine
  • Norepinephrine
  • Prazosin