Novel 2-alkylamino-1,4-benzoxazine derivatives as potent neuroprotective agents: structure-activity relationship studies

J Med Chem. 2005 Feb 24;48(4):1282-6. doi: 10.1021/jm040874m.

Abstract

2-Alkylamino-substituted-1,4-benzoxazine derivatives, a new class of potential neuroprotective agents, were synthesized and examined for their intrinsic cytotoxicity and their capacity to inhibit oxidative stress-mediated neuronal degeneration in vitro. Through structure-activity relationship studies, the 3,3-diphenyl-substituted-1,4-benzoxazine derivative 3l was identified as the optimal candidate, owing to its potent neuroprotective activity, without the manifestation of intrinsic cytotoxicity. Accordingly, 3l proved to be effective in an animal model of excitotoxic lesions in newborn mice.

MeSH terms

  • Animals
  • Animals, Newborn
  • Benzoxazines / chemical synthesis*
  • Benzoxazines / chemistry
  • Benzoxazines / pharmacology
  • Cell Line
  • Cerebral Palsy / chemically induced
  • Cerebral Palsy / drug therapy
  • Cerebral Palsy / pathology
  • Disease Models, Animal
  • Hippocampus / cytology
  • Mice
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship

Substances

  • Benzoxazines
  • Neuroprotective Agents
  • Reactive Oxygen Species