Design, synthesis and biological evaluation of novel chiral oxazino-indoles as potential and selective neuroprotective agents against Aß25-35-induced neuronal damage.

ABSTRACT

A series of chiral oxazino-indoles have been synthesized via a key intermolecular oxa-Pictet-Spengler reaction. These compounds exhibited significant and selective neuroprotective effects against Aß25-35-induced neuronal damage. This is the first report of evaluating the influence of chiral diversity of oxazino-indoles on their neuroprotective activities, with the structure-activity relationship been analyzed. The highly active compounds 3f, 3g, 4g, 4h, and 6b all performed over 90% cell protection, providing a new direction for the development of neuroprotective agents against Alzheimer's disease.