Arcamone F, Animati F, Capranico G, Lombardi P, Pratesi G, Manzini S, Supino R, Zunino F
Menarini Ricerche, Rome, Italy.
Pharmacol Ther. 1997 Oct-Dec;76(1-3):117-24. doi: 10.1016/s0163-7258(97)00096-x.
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-alpha-L-daunosaminyl-2'-deoxy-alpha-L-fucosyl)-4-demetho xy-adriamycinone, is presently undergoing clinical trials as a third generation antitumor anthracycline.
阿霉素是20世纪70年代初开始广泛应用于临床的一种主要抗癌药物。一系列广泛的类似物合成计划的实施，促成了耐受性更好的表柔比星以及高效抗白血病药物伊达比星的研发。近年来，基于已有的关于作用分子要求的信息，开展了一项新的合成计划，并结合了靶向药理学实验。获得了各种有趣的衍生物，即8-氟和10-氟化合物以及二糖。后一类化合物的生物活性强烈依赖于第二个糖部分柔红糖胺的取向（轴向与赤道向）。该类中的一个成员，即7-O-(4'-O-α-L-柔红糖胺基-2'-脱氧-α-L-岩藻糖基)-4-去甲氧基-阿霉素酮，目前正在作为第三代抗肿瘤蒽环类药物进行临床试验。
