Synthesis and bronchodilator activity of new quinazolin derivative

Eur J Med Chem. 2006 Mar;41(3):429-34. doi: 10.1016/j.ejmech.2005.09.010. Epub 2006 Jan 23.

Abstract

Taking lead from a naturally occurring quinazolin vasicine, a number of compounds were developed and evaluated for bronchodilator and anti-allergic activities. One of these compounds was 2,4-diethoxy-6,7,8,9,10,12-hexahydroazepino[2,1-b]quinazolin-12-one, hereinafter named 95-4, exhibited marked bronchodilator activity evaluated on contracted trachea or constricted tracheo-bronchial tree. On intestinal smooth muscle too it showed relaxant effect. Tracheal relaxant effect was not found to be mediated through beta-adrenoceptors. Cumulative dose-response study with acetylcholine and histamine indicated for its non-specific direct effect on smooth muscles. 95-4 was found to be more potent than theophylline and less to that of salbutamol on dose basis. Tested by a number of experimental models, it was found devoid of anti-allergic activity. It was also found to be free from any adverse effect. 95-4 due to its marked bronchial muscle relaxant effect can find use in conditions associated with spasm of bronchial muscles.

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry
  • Animals
  • Azepines / chemical synthesis*
  • Azepines / chemistry
  • Azepines / pharmacology*
  • Bronchodilator Agents / chemical synthesis*
  • Bronchodilator Agents / chemistry
  • Bronchodilator Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Guinea Pigs
  • Ileum / drug effects
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology

Substances

  • 2,4-diethoxy-6,7,8,9,10,12-hexahydroazepino(2,1-b)quinazolin-12-one
  • Alkaloids
  • Azepines
  • Bronchodilator Agents
  • Quinazolines
  • vasicine