Development of new mitomycin C and porfiromycin analogs

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Abstract
New mitomycin C and porfiromycin analogs were prepared by treating mitomycin A and N-methylmitomycin A with a variety of amines, including aziridines, allylamines, propargylamines, chloroalkylamines, hydroxyalkylamines, glycine derivatives, aralkylamines and heterocyclic amines. All analogs were evaluated against P-388 murine leukemia and selected ones were examined for their leukopenic properties. Certain analogs were superior to mitomycin C in potency, efficacy and therapeutic ratio in the P-388 assay. The most active substituents at the mitosane 7 position included aziridine, 2-methylaziridine, propargylamine, furfurylamine, methyl glycinate and 3-aminopyridine. Mitomycin A and the 7-aziridino, 7-(2-methylaziridino) and 3-aminopyridine analogs were less leukopenic than mitomycin C. Certain other analogs, including propargylamino and methyl glycinate, were highly leukopenic. The 3 compounds tested against B-16 melanoma in mice were significantly more effective than mitomycin C in this assay. Previously established structure-activity relationships were inadequate to account for all of the new data.