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.

Submitted by Héctor J De Jesús-Cortés on

Héctor J De Jesús-Cortés's picture
PDF versionPDF version
TitleDiscovery 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.
Publication TypeJournal Article
Year of Publication2014
AuthorsNaidoo, J, De Jesús-Cortés, H, Huntington, P, Estill, S, Morlock, LK, Starwalt, R, Mangano, TJ, Williams, NS, Pieper, AA, Ready, JM
JournalJ Med Chem
Volume57
Issue9
Pagination3746-54
Date Published2014 May 8
ISSN1520-4804
KeywordsAnimals, Area Under Curve, Carbazoles, Disease Models, Animal, Drug Discovery, Magnetic Resonance Spectroscopy, Mice, Mice, Inbred C57BL, Neuroprotective Agents, Parkinson Disease, Spectrometry, Mass, Electrospray Ionization, Substantia Nigra
Abstract

(-)-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.
DOI10.1021/jm401919s
Alternate JournalJ. Med. Chem.
PubMed ID24697290
PubMed Central IDPMC4206694
Grant ListR01 MH087986 / MH / NIMH NIH HHS / United States
R01 MH087986 / MH / NIMH NIH HHS / United States