The neuroprotective activity of 8-alkylamino-1,4-benzoxazine antioxidants

Eur J Pharmacol. 2001 Jul 27;424(3):189-94. doi: 10.1016/s0014-2999(01)01152-9.

Abstract

Antioxidant 8-alkylamino-1,4-benzoxazines, (R,S)-(3-tert-butyl-8-phenylethylamino-3,4-dihydro-2H-1,4-benzoxazin-5-yl) (phenyl) methanone (S 24429) and (R,S)-(3-cyclopentyl-8-benzylamino-3,4-dihydro-2H-1,4-benzoxazin-5-yl) (phenyl) methanone (S 24718), were prepared according to a two-step one-pot electrochemical procedure. These compounds had been selected from a previous study of structure/activity. Both compounds (1-100 microM) prevented the fall in ATP levels caused by 24 h of hypoxia in astrocytes. Both compounds (1 and 10 mg/kg i.p.) were powerful neuroprotective agents in protecting against the lesions induced by 15 microg S-bromo-willardiine injected into the cortex or white matter of 5-day old mice pups. In contrast, exifone, an antioxidant compound, was inactive at these doses. S 24429 and S 24718 appear to be novel neuroprotective agents, which are effective in a model of brain damage mimicking the lesions underlying cerebral palsy.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Alanine / administration & dosage
  • Alanine / analogs & derivatives*
  • Animals
  • Animals, Newborn
  • Antioxidants / pharmacology*
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Benzophenones / pharmacology
  • Benzoxazines
  • Brain / drug effects
  • Brain / pathology
  • Dose-Response Relationship, Drug
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Oxazines / pharmacology*
  • Oxygen / pharmacology
  • Rats

Substances

  • (3-cyclopentyl-8-benzylamino-3,4-dihydro-2H-1,4-benzoxazin-5-yl)phenylmethanone
  • (3-tert-butyl-8-phenylethylamino-3,4-dihydro-2H-1,4-benzoxazin-5-yl)phenylmethanone
  • Antioxidants
  • Benzophenones
  • Benzoxazines
  • Neuroprotective Agents
  • Oxazines
  • 5-bromowillardiine
  • exifone
  • Adenosine Triphosphate
  • Alanine
  • Oxygen