3'-deamino-3'-hydroxy-4'-deoxy-4'-amino doxorubicin and related daunorubicin

Claim 2

An anthracycline glycoside of the general formula (I): ##STR12## wherein R is hydrogen or hydroxy, and pharmaceutically acceptable salts thereof.

Claim 3

A compound according to claim 1, which is 3'-deamino-3'-hydroxy-4'-deoxy-4'-aminodaunorubicin or its hydrochloride.

Claim 4

A compound according to claim 1, which is 3'-deamino-3'-hydroxy-4'-deoxy-4'-aminodoxorubicin or its hydrochloride.

Claim 5

A process for the preparation of the compound of claim 1, in which 3'-deamino-4'-deoxy-3',4'-epiimino daunorubicin dissolved in acetone, is treated at room temperature and for 8 hours with p-toluensulfonic acid to afford 3'-deamino-3'-hydroxy-3'-epi-4'-deoxy-4'-amino daunorubicin which is subsequently reacted at room temperature and for 1 hour, in anhydrous methylene dichloride, with trifluoroacetic anhydride to obtain 3'-deamino-3'-hydroxy-3'-epi-4'-deoxy-4'-trifluoroacetamido daunorubicin which is converted, by treatment with trifluoromethanesulfonic anhydride at 0° C., in anhydrous methylene dichloride and in the presence of dry pyridine, into its 3'-O-trifluoromethanesulfonate derivative which after a mild alkaline treatment with 5% aqueous sodium bicarbonate, gives its 3',4'-oxazolidine derivative, from which upon acid hydrolysis with 0.5N hydrochloric acid, in methanolic solution at room temperature and for 1 hour, the desired 3'-deamino-3'-hydroxy-4'-deoxy-4'-amino daunorubicin (R=H) is isolated as its hydrochloride and, thereafter reacted with bromine in chloroform to obtain its 14-bromo derivative from which, after a mild hydrolysis at room temperature and for 48 hours under nitrogen with an aqueous solution of sodium formate, the compound of formula (I) (R=OH) is obtained as a free base and, by treatment with anhydrous methanolic hydrogen chloride, is isolated as its hydrochloride.

Claim 6

A pharmaceutical composition having antitumor activity against P388 leukemia tumors, comprising a therapeutically effective amount of the compound of claim 1 and inert carrier therefor.

Claim 7

A method of inhibiting the growth of P388 leukemia tumors comprising administering, to a mammal, afflicted with said tumor a therapeutically effective amount of the compound of claim 1.