A novel class of enkephalinase inhibitors containing a C-terminal sulfo group

J Med Chem. 1992 Feb 7;35(3):602-8. doi: 10.1021/jm00081a024.


A new series of sulfonic acids were synthesized and tested for their enkephalinase inhibitory activity. Among them, the most potent was N-(2-benzyl-3-mercaptopropionyl)metanilic acid 10i with an IC50 value of 0.27 nM. Several other analogues (10a,b,j,n,o,gg,hh) showed the inhibitory activity comparable to or greater than thiorphan (IC50 = 2.6 nM), a C-terminal carboxyl-containing inhibitor of enkephalinase. Thus compounds containing a C-terminal sulfo group, instead of the C-terminal carboxyl group, were found to show a remarkably high level of inhibition of enkephalinase. The analgesic activity of 10b, (S)-10b, and (R)-10b was also evaluated by the phenylbenzoquinone writhing test.

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Female
  • Mice
  • Molecular Conformation
  • Neprilysin / antagonists & inhibitors*
  • Rabbits
  • Structure-Activity Relationship
  • Sulfonic Acids / chemical synthesis
  • Sulfonic Acids / pharmacology


  • Analgesics
  • Enzyme Inhibitors
  • Sulfonic Acids
  • Neprilysin