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...

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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
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author 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.
author_facet 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.
author_sort Naidoo, Jacinth
collection PubMed
description [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.
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spelling pubmed-42066942014-10-23 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 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. J Med Chem [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. American Chemical Society 2014-04-03 2014-05-08 /pmc/articles/PMC4206694/ /pubmed/24697290 http://dx.doi.org/10.1021/jm401919s Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle 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-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(−)-P7C3-S243], with Improved Druglike Properties
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206694/
https://www.ncbi.nlm.nih.gov/pubmed/24697290
http://dx.doi.org/10.1021/jm401919s
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