Discovery of a neuroprotective chemical, (S)- N -(3-(3,6-Dibromo-9 H -carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(-)-P7C3-S243], with improved druglike properties

Jacinth Naidoo, Hector De Jesus-Cortes, Paula Huntington, Sandi Estill, Lorraine K. Morlock, Ruth Starwalt, Thomas J. Mangano, Noelle S. Williams, Andrew A. Pieper, Joseph M. Ready

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 Parkinsons 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.

Original languageEnglish (US)
Pages (from-to)3746-3754
Number of pages9
JournalJournal of Medicinal Chemistry
Volume57
Issue number9
DOIs
StatePublished - May 8 2014

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Amines
Neurons
Neurogenesis
Neuroprotective Agents
Substantia Nigra
Blood-Brain Barrier
Neurodegenerative Diseases
Parkinson Disease
Pharmaceutical Preparations
Protect-It
Lead
P7C3 compound
carbazole
Traumatic Brain Injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Discovery of a neuroprotective chemical, (S)- N -(3-(3,6-Dibromo-9 H -carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(-)-P7C3-S243], with improved druglike properties. / 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.

In: Journal of Medicinal Chemistry, Vol. 57, No. 9, 08.05.2014, p. 3746-3754.

Research output: Contribution to journalArticle

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. / Discovery of a neuroprotective chemical, (S)- N -(3-(3,6-Dibromo-9 H -carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(-)-P7C3-S243], with improved druglike properties. In: Journal of Medicinal Chemistry. 2014 ; Vol. 57, No. 9. pp. 3746-3754.
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