In search of new anticancer drugs. 13. Phosphonic and phosphinic analogs of ornithine

Phosphonic (4a,b) and phosphinic (5a-d) analogues of ornithine were synthesized and evaluated for their inhibitory activity against ornithine decarboxylase and against the lymphocytic leukemia P388. The title compounds possess a low degree of inhibition against rat liver ornithine decarboxylase as c...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 1985-09, Vol.28 (9), p.1350-1354
Main Authors: Sosnovsky, George, Lukszo, Jan, Gravela, Enrico, Zuretti, Maria Franca
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Chemical Phenomena
Chemistry
Leukemia P388 - drug therapy
Liver - enzymology
Male
Mice
Organophosphonates
Ornithine - analogs & derivatives
Ornithine Decarboxylase Inhibitors
Phosphinic Acids
Rats
Rats, Inbred Strains
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Phosphonic (4a,b) and phosphinic (5a-d) analogues of ornithine were synthesized and evaluated for their inhibitory activity against ornithine decarboxylase and against the lymphocytic leukemia P388. The title compounds possess a low degree of inhibition against rat liver ornithine decarboxylase as compared to alpha-(difluoromethyl)ornithine. Thus, compounds 4a and 5a inhibit by 40% the ornithine decarboxylase activity at a 5 mM concentration. The other derivatives are less potent. Compounds 4a, 4b, 5b, and 5d are inactive against P388 tumor in CD2F1 mice at doses of 50 and 150 mg/kg.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00147a041