Atwell G J, Rewcastle G W, Baguley B C, Denny W A
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
J Med Chem. 1990 May;33(5):1375-9. doi: 10.1021/jm00167a015.
9-Oxoxanthene-4-acetic acids are a class of antitumor agents effective against the mouse colon adenocarcinoma 38 in vivo. Within this class, 5-substituents on the xanthenone are known to enhance potency. To extend structure-activity relationships for the class, a series of derivatives bearing a wide variety of substituents at the 5-position have been prepared and evaluated. The results suggest that activity correlates better with the lipophilic properties of substituents rather than with their electronic properties. Generally, lipophilic substituents result in more active compounds, but there may be a size limitation on such substituents. The 5-methyl derivative is the most dose-potent of the analogues studied.
9-氧代氧杂蒽-4-乙酸是一类在体内对小鼠结肠腺癌38有效的抗肿瘤剂。在这类化合物中，已知占吨酮上的5-取代基可增强效力。为了扩展该类化合物的构效关系，已制备并评估了一系列在5-位带有各种取代基的衍生物。结果表明，活性与取代基的亲脂性而非电子性质的相关性更好。一般来说，亲脂性取代基会产生更具活性的化合物，但此类取代基可能存在尺寸限制。5-甲基衍生物是所研究类似物中剂量效力最高的。
