Elsevier

Pharmacology & Therapeutics

Volume 76, Issues 1–3, October–December 1997, Pages 117-124
Pharmacology & Therapeutics

New developments in antitumor anthracyclines

https://doi.org/10.1016/S0163-7258(97)00096-XGet rights and content

Abstract

Doxorubicin is a major anticancer agent introduced to extended clinical use in the early 1970s. The fulfillment of a wide program of analogue synthesis led to the development of the better tolerated epirubicin and of a highly potent antileukemic drug, idarubicin. In recent years, on the basis of the available information on the molecular requirements for action, a new synthetic program, coupled with target-oriented pharmacological experiments, was carried out. Various interesting derivatives, namely, the 8- and 10-fluoro compounds and the disaccharides, were obtained. The latter compounds exhibited a strong dependence of biological activity on the orientation (axial vs. equatorial) of the second sugar moiety, daunosamine. A member of this group, namely, 7-O-(4′-O-α-l-daunosaminyl-2′-deoxy-α-l-fucosyl)-4-demethoxy-adriamycinone, is presently undergoing clinical trials as a third generation antitumor anthracycline.

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