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) 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.
Stanek
J
J
Research Laboratories, Pharmaceuticals Division, Ciba-Geigy AG., Basel, Switzerland.
Frei
J
J
Mett
H
H
Schneider
P
P
Regenass
U
U
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003959:Diamines / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D065108:Ornithine Decarboxylase Inhibitors; D011412:Propanolamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003959:Diamines; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D011412:Propanolamines; C074203:3-(aminooxy)-2-fluoropropanamine