Synthesis and bioactivities of novel bicyclic thiophenes and 4,5,6,7-tetrahydrothieno[2,3-c]pyridines as inhibitors of tumor necrosis factor-alpha (TNF-alpha) production

Bioorg Med Chem Lett. 2002 Aug 5;12(15):1897-900. doi: 10.1016/s0960-894x(02)00332-3.

Abstract

We synthesized bicyclic thiophenes and 4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives, and evaluated for their ability to inhibit LPS-stimulated production of TNF-alpha. Several compounds revealed excellent in vivo activity. Furthermore, an effective compound was found in adjuvant-induced arthritic model (AIA) of rat.

MeSH terms

  • Animals
  • Arthritis, Experimental / drug therapy
  • Bridged Bicyclo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / pharmacology
  • Disease Models, Animal
  • Inhibitory Concentration 50
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis*
  • Thiophenes / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Bridged Bicyclo Compounds
  • Lipopolysaccharides
  • Pyridines
  • Thiophenes
  • Tumor Necrosis Factor-alpha