Thienopyridines: nitric oxide synthase inhibitors with potent in vivo activity

Bioorg Med Chem Lett. 2001 Apr 23;11(8):1027-30. doi: 10.1016/s0960-894x(01)00120-2.

Abstract

5-Substituted 7-amino-4,5-tetrahydrothieno[2,3-c]pyridines and 6-substituted 4-amino-6,7-dihydrothieno[3,2-c]pyridines were shown to be exceptionally potent inhibitors of inducible and neuronal nitric oxide synthase. Selectivity and potency could be modulated by variation of the 5- or 6-substituent. Compound 3e showed potent in vivo inhibition of iNOS.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Cells, Cultured
  • Cerebellum / cytology
  • Cyclopropanes / chemical synthesis
  • Cyclopropanes / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Humans
  • In Vitro Techniques
  • Inhibitory Concentration 50
  • Lipopolysaccharides / pharmacology
  • Models, Animal
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitrites / agonists
  • Pyridines / chemical synthesis
  • Pyridines / pharmacology*
  • Rats
  • omega-N-Methylarginine / pharmacology

Substances

  • Cyclopropanes
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Nitrites
  • Pyridines
  • omega-N-Methylarginine
  • NOS1 protein, human
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nos1 protein, rat
  • Nos2 protein, rat