In the search for new anticancer drugs. 13. Phosphonic and phosphinic analogues of ornithine

Article abstract of DOI:10.1021/jm00147a041

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 α-(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.