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. Epub 2014 Apr 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Area Under Curve
  • Carbazoles / pharmacology*
  • Disease Models, Animal
  • Drug Discovery
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents / pharmacokinetics
  • Neuroprotective Agents / pharmacology*
  • Parkinson Disease / pathology
  • Spectrometry, Mass, Electrospray Ionization
  • Substantia Nigra / pathology

Substances

  • Carbazoles
  • Neuroprotective Agents
  • P7C3 compound