M. Largeron et al., Synthesis and in vitro evaluation of new 8-amino-1,4-benzoxazine derivatives as neuroprotective antioxidants, J MED CHEM, 42(24), 1999, pp. 5043-5052
A series of new 8-amino-1,4-benzoxazine derivatives 5a-o was synthesized an
d examined for their intrinsic cytotoxicity and their capacity to inhibit o
xidative stress-mediated neuronal degeneration in neuronal cell cultures. I
n particular, substituent effects at the 3- and 8-positions of the 1,4-benz
oxazine ring were investigated by in vitro evaluation.. In this aim, 3-alky
l substituents seemed to be essential for efficient neuroprotective activit
y. Furthermore, within the subseries of substituted S-alkyl benzoxazines, t
he most active derivatives were those bearing an 8-benzylamino substituent.
From the combined results of both toxicity and neuroprotection expressed i
n terms of the safety index, 8-benzylamino-substituted-3-alkyl-1,4-benzoxaz
ines were identified as the most promising compounds, owing to their potent
neuroprotective activity without the manifestation of intrinsic cytotoxici
ty.