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

Antioxidant 8-alkylamino-1,4-benzoxazines, (R,S)-(3-tert-butyl-8-phenylethy lamino-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) (ph enyl) methanone (S 24718), were prepared according to a two-step one-pot el ectrochemical procedure. These compounds had been selected from a previous study of structure/activity. Both compounds (1-100 muM) prevented the fall in ATP levels caused by 24 h of hypoxia in astrocytes. Both compounds (1 an d 10 mg/kg i.p.) were powerful neuroprotective agents in protecting against the lesions induced by 15 mug S-bromo-willardiine injected into the cortex or white matter of 5-day old mice pups. In contrast, exifone, an antioxida nt 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 damag e mimicking the lesions underlying cerebral palsy. (C) 2001 Elsevier Scienc e B.V. All rights reserved.