Plant antitumor agents. 18. Synthesis and biological activity of camptothecin analogs
作者:Mansukh C. Wani、Peter E. Ronman、James T. Lindley、Monroe E. Wall
DOI:10.1021/jm00179a016
日期:1980.5
Four analogues, 10-methoxy (20), 12-aza (29), benz[j] (36), and 18-methoxy (38), of camptothecin were obtained by total synthesis. The two water-soluble analogues, 10-[(carboxymethyl)oxy]- (24) and 10-[2'-(diethylamino)-ethoxy]-20(S)-camptothecin (26), with intact ring E were prepared from natural 10 hydroxycamptothecin (3). In general, there was a good correlation between in vitro 9KB cytotoxicity
通过全合成获得喜树碱的四个类似物,即10-甲氧基(20),12-氮杂(29),苯并[j](36)和18-甲氧基(38)。由完整的环E制备了两个水溶性类似物10-[(羧甲基)氧基]-(24)和10- [2'-(二乙氨基)-乙氧基] -20(S)-喜树碱(26)。天然10羟基喜树碱(3)。通常,P-388白血病系统的体外9KB细胞毒性与活性之间存在良好的相关性。尽管氮杂类似物29在P-388中的活性仅比天然喜树碱(1)高得多,但18-甲氧基类似物38的活性却与1相似。水溶性衍生物24是无活性的。胺盐酸盐26在高剂量水平下显示出优异的活性。这可能是由于其水解为3。dl-Camptothecin(17)的活性大约是1的一半,