Adams N, Blake C, Broadhurst M J, Bushnell D J, Hassall C H, Hartmann H R, Keech E, Stratton A R, Thomas G J
Roche Products Limited, Welwyn Garden City, Hertfordshire, England.
J Med Chem. 1990 Sep;33(9):2380-4. doi: 10.1021/jm00171a011.
A number of 4-demethoxyanthracyclines having hydroxylalkyl functions at the 9-position have previously been synthesized and shown to have potent antitumor activity. A series of carbamate derivatives of these (hydroxyalkyl)anthracyclines have now been prepared, many of which possess considerably greater efficacy in an L-1210 leukemia test system than do the parent alcohols or the known anthracyclines daunorubicin (1), doxorubicin (2), and 4-demethoxydaunorubicin (3). Phenylcarbamate 8a was more active than methyl analogue 8b, while the 4'-deoxy and 4'-epi phenylcarbamates 17 and 18 showed particularly high efficacy at optimal dose levels similar to that of doxorubicin. Secondary carbamates were more potent, with the 13R isomer 23 having significantly higher efficacy than 13S analogue 24.
先前已合成了多种在9位具有羟烷基官能团的4-去甲氧基蒽环类化合物，并显示出具有强大的抗肿瘤活性。现在已经制备了这些（羟烷基）蒽环类化合物的一系列氨基甲酸酯衍生物，其中许多在L-1210白血病测试系统中的疗效比母体醇类或已知的蒽环类化合物柔红霉素（1）、阿霉素（2）和4-去甲氧基柔红霉素（3）要高得多。苯基氨基甲酸酯8a比甲基类似物8b更具活性，而4'-脱氧和4'-表苯基氨基甲酸酯17和18在与阿霉素相似的最佳剂量水平下显示出特别高的疗效。仲氨基甲酸酯更具效力，13R异构体23的疗效明显高于13S类似物24。
