Discovery of a Neuroprotective Chemical, (S)-N-(3-(3,6-Dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(鈭?-P7C3-S243], with Improved Druglike Properties
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- 作者：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
- 刊名：Journal of Medicinal Chemistry
- 出版年：2014
- 出版时间：May 8, 2014
- 年：2014
- 卷：57
- 期：9
- 页码：3746-3754
- 全文大小：451K
- 年卷期：v.57,no.9(May 8, 2014)
- ISSN：1520-4804
文摘
(鈭?-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鈥檚 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鈥揵rain barrier. As such, it represents a valuable lead compound for the development of drugs to treat neurodegenerative diseases and traumatic brain injury.