Design and synthesis of orally active inhibitors of TNF synthesis as anti-rheumatoid arthritis drugs

Bioorg Med Chem Lett. 2003 Nov 17;13(22):3951-4. doi: 10.1016/j.bmcl.2003.08.076.

Abstract

A novel series of TNF inhibitors was identified based on the screening of existing MMP inhibitor libraries. Further SAR optimization led to the discovery of a novel lead compound. Its synthesis, efficacy in experimental animal models, and pharmacokinetic data are discussed.

MeSH terms

  • Animals
  • Antirheumatic Agents / chemical synthesis*
  • Antirheumatic Agents / chemistry
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Disease Models, Animal
  • Drug Design
  • Humans
  • Mice
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha