PLANT ANTITUMOR AGENTS .23. SYNTHESIS AND ANTILEUKEMIC ACTIVITY OF CAMPTOTHECIN ANALOGS
PLANT ANTITUMOR AGENTS .23. SYNTHESIS AND ANTILEUKEMIC ACTIVITY OF CAMPTOTHECIN ANALOGS
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DOI：
10.1021/jm00161a035
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发表时间：
1986-11-01
影响因子：
7.3
通讯作者：
WALL, ME
中科院分区：
文献类型：
--
作者：
WANI, MC;NICHOLAS, AW;WALL, ME
制备了 20(S)-喜树碱的八种光学活性类似物和九种外消旋环 A 修饰类似物，并评估了其在 L-1210 白血病系统中的抗肿瘤活性。 A环单取代和双取代类似物在活性和效力方面表现出很大的差异。研究发现，在 9、10 或 11 位被 NH2 或 OH 单取代产生的化合物的活性远高于母体化合物喜树碱，而在 12 位的取代则大大降低了活性。一般来说，A环的去取代大大降低了抗白血病活性。用杂环（噻吩或吡啶）取代环 A 会产生仅具有中等活性的类似物。
Eight optically active and nine racemic ring A modified analogues of 20(S)-camptothecin were prepared and evaluated for antitumor activity in the L-1210 leukemia system. The ring A mono- and disubstituted analogues displayed a wide variance in activity and potency. It was found that monosubstitution by NH2 or OH at positions 9, 10, or 11 yielded compounds with activity much higher than the parent compound, camptothecin, whereas substitution at position 12 greatly reduced activity. In general, disubstitution in ring A greatly reduced antileukemic activity. Replacement of ring A by heterocyclic rings (thiophene or pyridine) leads to analogues with only moderate activity.