Selective heterocyclic amidine inhibitors of human inducible nitric oxide synthase

Bioorg Med Chem Lett. 2001 Oct 8;11(19):2651-3. doi: 10.1016/s0960-894x(01)00523-6.

Abstract

The potency and selectivity of a series of 5-hetero-2-iminohexahydroazepines were examined as inhibitors of the three human NOS isoforms. The effect of ring substitution of the 5-carbon for a heteroatom is presented. Potencies (IC(50)'s) for these inhibitors are in the low micromolar range for hi-NOS with some examples exhibiting a 500x selectivity versus hec-NOS.

MeSH terms

  • Azepines / chemical synthesis
  • Azepines / chemistry
  • Azepines / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Isoenzymes / antagonists & inhibitors*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II
  • Structure-Activity Relationship

Substances

  • Azepines
  • Enzyme Inhibitors
  • Isoenzymes
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II