4-Demethoxy-4-hydroxydaunorubicin 6-methyl ether and 11-methyl ether, two active isomers of daunorubicin.

The preparation of two isomers of daunorubicin, one having a completely chelated dihydroxyanthraquinone chromophor (III) and one have having such a chromophor in a emichelated form (IV), is reported. The former is as active as daunorubicin, the latter shows a considerable activity, however at much higher doses.

Doxorubicin 14-ethers.

The synthesis and the antitumor activities of a group of doxorubicin (adriamycin) 14-ethers are reported. The new compounds were found to have an activity similar to that of daunorubicin, at somewhat higher doses, but inferior to that of doxorubicin.

Synthesis and antitumour activity of new daunorubicin and adriamycin analogues.

A new synthetic procedure for the preparation of daunorubicin and adriamycin analogues bearing different substituents on ring D, has been developed. The new compounds display outstanding efficacy against experimental tumours of mice.

Synthesis and antitumor activity of 4-demethoxyadriamycin and 4-demethoxy-4' -epiadriamycin.

Two new analogs of adriamycin have been obtained by chemical synthesis, 4-demethoxyadriamycin and 4-demethoxy-4' -epiadriamycin. Both compounds were highly effective against experimental mouse tumors at doses about ten times lower than those effective for adriamycin. At the optimal dose, 4-demethoxyadriamycin displayed antitumor activity similar to that of adriamycin in solid Sarcoma 180 (S180), L1210, P388, and Gross leukemias, and mammary carcinoma, while it did not markedly inhibit the growth of Moloney sarcoma virus-induced sarcoma in mice treated before the virus infection. At the optimal dose, 4-demethoxy-4' -epiadriamycin was as active as adriamycin against L1210, P388,and Gross leukemias, and less active against solid S180. The results show that anthracycline derivatives characterized by the absence of the methoxyl group at the C-4 position are markedly more potent than the parent compound, and may exhibit a differential antitumor effect on a number of mouse tumors.

Synthesis and antitumor activity of 4-demethoxydaunorubicin, 4-demethoxy-7,9-diepidaunorubicin, and their beta anomers.

Four new derivatives of daunorubicin, characterized by the absence of the methoxyl group at the C-4 position, have been obtained by chemical synthesis. 4-Demethoxydaunorubicin (NSC-256439) was effective against L1210 and Gross leukemias and ascites and solid Sarcoma 180 at doses four to eight times lower than those effective for daunorubicin. The beta anomer of 4-demethoxydaunorubicin was active at doses 13and eight times higher than those of its corresponding alpha anomer against L1210 and Gross leukemias respectively. 4-Demethoxy-7,9-diepidaunorubicin and its beta anomer were devoid of any biologic activity at the doses tested.