Novel inhibitors of prolyl 4-hydroxylase. 2. 5-Amide substituted pyridine-2-carboxylic acids

J Med Chem. 1992 Mar 6;35(5):804-7. doi: 10.1021/jm00083a002.


A series of 5-[(arylcarbonyl)amino]- and 5-(arylcarbamoyl)pyridine-2-carboxylic acids has been prepared and tested for activity as inhibitors of the enzyme prolyl 4-hydroxylase (EC All the analogues prepared were inhibitors of the enzyme in vitro, the best compounds being equipotent with the known inhibitor pyridine-2,5-dicarboxylic acid (9). Like 9 these amidic analogues were not active in a cultured embryonic chick tendon cell model, considered to be a predictor of in vivo activity. The activity of the amides is not consistent with the model described for the mode of action of 9 with the enzyme and aspects of this are discussed.

Publication types

  • Comparative Study

MeSH terms

  • Amides / chemical synthesis
  • Amides / pharmacology*
  • Molecular Structure
  • Picolinic Acids / chemistry*
  • Picolinic Acids / pharmacology
  • Procollagen-Proline Dioxygenase / antagonists & inhibitors*
  • Pyridines / pharmacology
  • Structure-Activity Relationship


  • Amides
  • Picolinic Acids
  • Pyridines
  • 2,5-Pyridinedicarboxylic acid
  • Procollagen-Proline Dioxygenase
  • picolinic acid