Inhibition of Pig Kidney L-aromatic Amino Acid Decarboxylase by 2,3-methano-m-tyrosines

J Med Chem. 1992 Apr 17;35(8):1410-7. doi: 10.1021/jm00086a009.

Abstract

Both racemic (E)- and (Z)-2,3-methano-m-tyrosines (9E and 9Z) have been synthesized from a common intermediate, monoester (Z)-1-(ethoxycarbonyl)-2-[3-[(2-methoxyethoxy)methoxy]phenyl] cyclopropanecarboxylic acid (5). Quinine and ephedrine, respectively, were used to resolve their N-tert-butoxycarbonyl (Boc) derivatives. Among the compounds prepared, the (+)-(E)-diastereomer of 9 is the most potent inhibitor of L-aromatic amino acid decarboxylase (Dopa decarboxylase), having a Ki of 22 microM, with the (-)-Z-diastereomer (9Z) second at Ki = 49 microM. (+)-9E is a 45-fold more potent inhibitor of DDC than its acyclic analogue, D-m-tyrosine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatic Amino Acid Decarboxylase Inhibitors*
  • Chromatography, High Pressure Liquid
  • Dopa Decarboxylase / isolation & purification
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Kidney / enzymology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Swine
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemical synthesis
  • Tyrosine / pharmacology

Substances

  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Enzyme Inhibitors
  • 2,3-methano-3-tyrosine
  • Tyrosine
  • Dopa Decarboxylase