Novel inhibitors of prolyl 4-hydroxylase

J Med Chem. 1992 Mar 6;35(5):800-4. doi: 10.1021/jm00083a001.


A series of 5-acyl sulfonamides derived from pyridine-2,5-dicarboxylic acid (15) has been prepared and several members of this series have been shown to be more potent, in vitro, as inhibitors of prolyl 4-hydroxylase than 15. Several chain-extended pyridinedicarboxylic acids have also been prepared and shown to be potent inhibitors of prolyl 4-hydroxylase. The structure-activity in both these series is discussed. The results indicate that the 5-carboxylic acid binding site, in the enzyme, can accept a carboxylic acid or an acyl sulfonamide equally well. This indicates a much greater degree of freedom in this distal carboxylic acid binding site than is predicted by the current theoretical model of the active site.

Publication types

  • Comparative Study

MeSH terms

  • Binding Sites
  • Molecular Structure
  • Procollagen-Proline Dioxygenase / antagonists & inhibitors*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*


  • Pyridines
  • Sulfonamides
  • 2,5-Pyridinedicarboxylic acid
  • Procollagen-Proline Dioxygenase