Design, synthesis, and urease inhibition studies of some 1,3,4-oxadiazoles and 1,2,4-triazoles derived from mandelic acid

J Enzyme Inhib Med Chem. 2010 Aug;25(4):572-6. doi: 10.3109/14756360903389864.

Abstract

Some new structural type inhibitors of urease, i.e. 2,5-disubstituted-1,3,4-oxadiazoles (4a-e) and 4,5-disubstituted-1,2,4-triazole-3-thiones (5a-e) were synthesized in two steps from mandelic acid hydrazides (2a-e) and aryl isothiocyanates. The hydrazides in turn were synthesized from mandelic acid via esterification. Compounds 4a-e and 5a-e were evaluated against jack bean urease. Compounds 4d, 5b, and 5d were found to be more potent, with IC(50) values of 16.1 +/- 0.12 microM, 18.9 +/- 0.188 microM, and 16.7 +/- 0.178 microM, respectively, when compared to the standard (thiourea; IC(50) = 21.0 +/- 0.011 microM). These compounds may be subjected to further investigations for the development of antiulcer drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Ulcer Agents
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Mandelic Acids / chemistry
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / pharmacology
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology
  • Urease / antagonists & inhibitors*

Substances

  • Anti-Ulcer Agents
  • Enzyme Inhibitors
  • Mandelic Acids
  • Oxadiazoles
  • Triazoles
  • 1,2,4-triazole
  • Urease
  • mandelic acid