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

doi:10.1021/jm401919s

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 journal › Article › peer-review

57 Scopus citations

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 language	English (US)
Pages (from-to)	3746-3754
Number of pages	9
Journal	Journal of Medicinal Chemistry
Volume	57
Issue number	9
DOIs	https://doi.org/10.1021/jm401919s
State	Published - May 8 2014

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm401919s

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Naidoo, J., De Jesus-Cortes, H., Huntington, P., Estill, S., Morlock, L. K., Starwalt, R., Mangano, T. J., Williams, N. S., Pieper, A. A., & Ready, J. M. (2014). 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. Journal of Medicinal Chemistry, 57(9), 3746-3754. https://doi.org/10.1021/jm401919s

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

Research output: Contribution to journal › Article › peer-review

Naidoo, J, De Jesus-Cortes, H, Huntington, P, Estill, S, Morlock, LK, Starwalt, R, Mangano, TJ, Williams, NS, Pieper, AA & Ready, JM 2014, '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', Journal of Medicinal Chemistry, vol. 57, no. 9, pp. 3746-3754. https://doi.org/10.1021/jm401919s

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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.",

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AU - Naidoo, Jacinth

AU - De Jesus-Cortes, Hector

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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

Abstract

ASJC Scopus subject areas

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