10,11-亚甲二氧基-14-氮杂喜树碱的合成与生物学评价

Synthesis and biological evaluation of 10,11-methylenedioxy-14-azacamptothecin.

作者信息

Elban Mark A, Sun Wenyue, Eisenhauer Brian M, Gao Rong, Hecht Sidney M

机构信息

Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, USA.

出版信息

Org Lett. 2006 Aug 3;8(16):3513-6. doi: 10.1021/ol0611604.

DOI:10.1021/ol0611604

PMID:16869648

Abstract

[reaction: see text] 10,11-Methylenedioxy-14-azacamptothecin, a potent analogue of the antitumor agent camptothecin (CPT), has been prepared via a key condensation between AB and DE ring precursors. The biological testing of this compound validated a strategy for modulation of the off-rate of camptothecin analogues from the topoisomerase-DNA-CPT ternary complex via structural modification.

摘要

[反应：见正文]10,11-亚甲基二氧基-14-氮杂喜树碱是抗肿瘤药物喜树碱（CPT）的一种有效类似物，它是通过AB环和DE环前体之间的关键缩合反应制备的。该化合物的生物学测试验证了一种通过结构修饰来调节喜树碱类似物从拓扑异构酶-DNA-CPT三元复合物解离速率的策略。