Synthesis of some novel potent and selective catechol O-methyltransferase inhibitors

J Med Chem. 1989 Apr;32(4):841-6. doi: 10.1021/jm00124a017.


A series of disubstituted catechol derivatives was synthesized and tested as potential COMT inhibitors. The most active compounds were more than 1000 times more potent (IC50 = 3-6 nM) in vitro than the known COMT inhibitor, 3',4'-dihydroxy-2-methylpropiophenone (U 0521, IC50 = 6000 nM). The new compounds were also highly selective COMT inhibitors with no activity against other essential enzymes involved in the synthesis and metabolism of catecholamines.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / enzymology
  • Catechol O-Methyltransferase Inhibitors*
  • Catechols / chemical synthesis*
  • Catechols / pharmacology
  • Chemical Phenomena
  • Chemistry
  • Female
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship


  • Catechol O-Methyltransferase Inhibitors
  • Catechols