Design, synthesis and biological evaluation of benzimidazole/benzothiazole and benzoxazole derivatives as cyclooxygenase inhibitors

Bioorg Med Chem Lett. 2003 Feb 24;13(4):657-60. doi: 10.1016/s0960-894x(02)01006-5.

Abstract

We have synthesised a series of 2-[[2-alkoxy-6-pentadecylphenyl)methyl]thio]-1H-benzimidazoles/benzothiazoles and benzoxazoles from anacardic acid and investigated their ability to inhibit human cyclooxygenase-2 enzyme (COX-2). The active compounds were screened for cyclooxygenase-1 (COX-1) inhibition. Compound 13 is 384-fold and 19 is more than 470-fold selective towards COX-2 compared to COX-1. Thus, this class of compounds may serve as excellent candidates for selective COX-2 inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / pharmacology
  • Benzothiazoles
  • Benzoxazoles / chemical synthesis
  • Benzoxazoles / pharmacology
  • Blood / metabolism
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / chemical synthesis*
  • Cyclooxygenase Inhibitors / pharmacology
  • Drug Evaluation, Preclinical
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Isoenzymes / antagonists & inhibitors
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / pharmacology

Substances

  • Benzimidazoles
  • Benzothiazoles
  • Benzoxazoles
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Heterocyclic Compounds
  • Isoenzymes
  • Membrane Proteins
  • Thiazoles
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • benzothiazole