New substituted 1,4-benzoxazine derivatives with potential intracellular calcium activity

J Med Chem. 1998 Aug 13;41(17):3142-58. doi: 10.1021/jm970795t.

Abstract

Substituted 1,4-benzoxazines bearing an amino side chain at the 2-position were prepared and were found to have a moderate activity on intracellular calcium. Of the compounds studied it was found that those which possess a homoveratrylamino moiety exhibited superior potency. The chain length and the nature of the amine (4-fluorophenylpiperazine, 4-fluorobenzhydryloxyethylamine, N-substituted homoveratrylamine) is discussed. The 4-benzyl-3, 4-dihydro-2-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-2H-1, 4-benzoxazine (3c) is the most potent derivative of the series with a ratio of IC50 values against PE (phenylephrine) and K+ of 2.1. Under these test conditions a ratio near 1 indicates potential intracellular calcium activity while a ratio greater than 100 an action on extracellular calcium influx.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / physiology
  • Calcium / metabolism*
  • Calcium Channel Blockers / chemical synthesis*
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / pharmacology
  • Drug Design
  • In Vitro Techniques
  • Male
  • Molecular Structure
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • Oxazines / chemical synthesis*
  • Oxazines / chemistry
  • Oxazines / pharmacology*
  • Phenylephrine / pharmacology
  • Rabbits
  • Renal Artery / drug effects
  • Renal Artery / physiology
  • Second Messenger Systems
  • Structure-Activity Relationship
  • Vasoconstriction / drug effects

Substances

  • Calcium Channel Blockers
  • Oxazines
  • Phenylephrine
  • Calcium