Synthesis of L-thiocitrulline, L-homothiocitrulline, and S-methyl-L-thiocitrulline: A New Class of Potent Nitric Oxide Synthase Inhibitors

J Med Chem. 1994 Apr 1;37(7):885-7. doi: 10.1021/jm00033a004.

Abstract

Nitric oxide synthase catalyzes the NADPH- and O2-dependent conversion of L-arginine to L-citrulline and nitric oxide. L-Thiocitrulline, L-homothiocitrulline, and S-methyl-L-thiocitrulline, novel citrulline analogs, have been synthesized and are shown to be potent inhibitors of both the constitutive brain and the inducible smooth muscle isoforms of nitric oxide synthase. Although many N omega-monosubstituted arginine derivatives inhibit nitric oxide synthase, inhibitory citrulline derivatives have not previously been reported. S-Methyl-L-thiocitrulline is significantly more potent than N omega-methyl-L-arginine, the prototypic nitric oxide synthase inhibitor.

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors*
  • Amino Acid Oxidoreductases / metabolism
  • Aminocaproates*
  • Aminocaproic Acid*
  • Animals
  • Binding Sites
  • Brain / enzymology
  • Citrulline / analogs & derivatives*
  • Citrulline / chemical synthesis
  • Citrulline / pharmacology
  • Heme / metabolism
  • Iron / metabolism
  • Muscle, Smooth / enzymology
  • Nitric Oxide Synthase
  • Rats
  • Thiourea / analogs & derivatives*
  • Thiourea / chemical synthesis
  • Thiourea / pharmacology

Substances

  • Aminocaproates
  • homothiocitrulline
  • thiocitrulline
  • homocitrulline
  • Citrulline
  • Heme
  • Iron
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Thiourea
  • S-methylthiocitrulline
  • Aminocaproic Acid