Synthesis and 5 alpha-reductase inhibitory activity of 8-substituted benzo[f]quinolinones derived from palladium mediated coupling reactions

Bioorg Med Chem Lett. 1998 Feb 17;8(4):395-8. doi: 10.1016/s0960-894x(98)00035-3.

Abstract

Benzoquinolinones have been shown to be potent, selective inhibitors of the Type I 5 alpha-reductase enzyme, which is responsible for the production of dihydrotestosterone from testosterone localized in the scalp. In an effort to identify compounds that demonstrate inhibition of both 5 alpha-reductase isozymes, we have employed 8-bromobenzoquinolinone as an advanced intermediate for participation in a variety of palladium mediated carbon-carbon bond forming reactions. By varying the 8-substituent it is possible to alter the selectivity profile of the series.

MeSH terms

  • Cholestenone 5 alpha-Reductase
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Male
  • Oxidoreductases / antagonists & inhibitors*
  • Palladium / chemistry*
  • Prostate / drug effects
  • Prostate / enzymology
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Scalp / drug effects
  • Scalp / enzymology
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Quinolones
  • Palladium
  • Oxidoreductases
  • Cholestenone 5 alpha-Reductase