Synthesis, enantioseparation and pharmacological activity of 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones

Arzneimittelforschung. 2002;52(1):27-33. doi: 10.1055/s-0031-1299852.

Abstract

4-Aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione derivatives (1-8) have been prepared by modified Biginelli reaction from 5,5-dimethyl-1,3-cyclohexanedione, the aromatic aldehydes and thiourea. The structures of the compounds were confirmed by spectroscopic and elemental analysis. Racemic compounds were resolved into their enantiomers by HPLC using an amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase in the normal phase mode. The calcium antagonist activities of the compounds were determined by the tests performed on isolated rat ileum and lamb carotid artery. Compounds 2, 3, 4 and 6 were the most active compounds on isolated rat ileum. Compounds 2 and 3 were significantly active on lamb carotid artery.

MeSH terms

  • Animals
  • Calcium Channel Blockers / chemical synthesis*
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / pharmacology*
  • Carotid Arteries / drug effects
  • Chromatography, High Pressure Liquid
  • Female
  • In Vitro Techniques
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Molecular Weight
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Potassium Chloride / pharmacology
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Rats
  • Sheep
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet
  • Stereoisomerism

Substances

  • Calcium Channel Blockers
  • Indicators and Reagents
  • Quinazolines
  • Potassium Chloride