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

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)...

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Veröffentlicht in:	Journal of medicinal chemistry 1992-04, Vol.35 (8), p.1339-1344
Hauptverfasser:	Stanek, Jaroslav, Frei, Joerg, Mett, Helmut, Schneider, Peter, Regenass, Urs
Format:	Artikel
Sprache:	eng
Schlagworte:	Aliphatic compounds Animals Cell Division - drug effects Chemistry Diamines - chemical synthesis Diamines - pharmacology Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Exact sciences and technology Humans Liver - drug effects Liver - enzymology Organic chemistry Ornithine Decarboxylase Inhibitors Preparations and properties Propanolamines - chemical synthesis Propanolamines - chemistry Propanolamines - pharmacology Rats Structure-Activity Relationship Tumor Cells, Cultured - drug effects
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Zusammenfassung:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm00086a003