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

(−)-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 mod...

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Veröffentlicht in:Journal of medicinal chemistry 2014-05, Vol.57 (9), p.3746-3754
Hauptverfasser: 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
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Sprache:eng
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Zusammenfassung:(−)-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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm401919s