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

  • J Med Chem. 2014 May 8;57(9):3746-54. doi: 10.1021/jm401919s.
Jacinth Naidoo  1 ,  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
Affiliations
  • 1. Departments of †Biochemistry and ‡Neuroscience, University of Texas Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
PMID: 24697290 DOI: 10.1021/jm401919s
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.

Products