Discovery of a Neuroprotective Chemical, (S)?N?(3-(3,6- Dibromo?9H?carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2- amine [(?)-P7C3-S243], with Improved Druglike Properties

摘要

(?)-P7C3-S243 is a neuroprotective aminopropyl carbazole with improved druglike properties compared with previously reported compounds in the P7C3 class. It protects developing neurons in a mouse model of hippocampal neurogenesis and protects mature neurons within the substantia nigra in a mouse model of Parkinson’s disease. A short, enantioselective synthesis provides the neuroprotective agent in optically pure form. It is nontoxic, orally bioavailable, metabolically stable, and able to cross the blood?brain barrier. As such, it represents a valuable lead compound for the development of drugs to treat neurodegenerative diseases and traumatic brain injury.