Cargando…

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

[Image: see text] (−)-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 ni...

Descripción completa

Detalles Bibliográficos
Autores principales: Naidoo, Jacinth, De Jesus-Cortes, Hector, Huntington, Paula, Estill, Sandi, Morlock, Lorraine K., Starwalt, Ruth, Mangano, Thomas J., Williams, Noelle S., Pieper, Andrew A., Ready, Joseph M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206694/
https://www.ncbi.nlm.nih.gov/pubmed/24697290
http://dx.doi.org/10.1021/jm401919s
Descripción
Sumario:[Image: see text] (−)-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.