2-substituted 3-(aminooxy)propanamines as inhibitors of ornithine decarboxylase: synthesis and biological activity

J Stanek; J Frei; H Mett; P Schneider; U Regenass

doi:10.1021/jm00086a003

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.

Authors

J Stanek¹, J Frei, H Mett, P Schneider, U Regenass

Affiliation

¹ Research Laboratories, Pharmaceuticals Division, Ciba-Geigy AG., Basel, Switzerland.

PMID: 1573631
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