2-substituted 3-(aminooxy)propanamines as Inhibitors of Ornithine Decarboxylase: Synthesis and Biological Activity

J Med Chem. 1992 Apr 17;35(8):1339-44. doi: 10.1021/jm00086a003.

Abstract

1-Amino-3-(aminooxy)-2-propanol (6a) has been synthesized and found to inhibit rat liver ornithine decarboxylase (ODC) with an IC50 in the nanomolar range. Compound 6a served as a basis for the design of new enzyme inhibitors, which led to the identification of 3-(aminooxy)-2-fluoropropanamine (15) as a new powerful enzyme blocker. Compound 15 inhibited ODC at 3 times lower concentrations than 6a and 3-(aminooxy)propanamine (APA), and it was superior to APA as an antiproliferative agent in inhibiting the growth of human T24 bladder carcinoma cells in vitro.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Diamines / chemical synthesis*
  • Diamines / pharmacology
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Liver / drug effects
  • Liver / enzymology
  • Ornithine Decarboxylase Inhibitors*
  • Propanolamines / chemical synthesis*
  • Propanolamines / chemistry
  • Propanolamines / pharmacology
  • Rats
  • Structure-Activity Relationship
  • Tumor Cells, Cultured / drug effects

Substances

  • Diamines
  • Enzyme Inhibitors
  • Ornithine Decarboxylase Inhibitors
  • Propanolamines
  • 3-(aminooxy)-2-fluoropropanamine