(19S)-10,19-diethyl-7,19-dihydroxy-8-prop-2-enyl-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione | 852213-06-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: (19S)-10,19-diethyl-7,19-dihydroxy-8-prop-2-enyl-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
• CAS: 852213-06-0
• 化学式: C₂₅H₂₄N₂O₅
• 分子量: 432.476
• InChiKey: GWGTZDOPYOSSLR-VWLOTQADSA-N

物化性质

• 沸点：
  802.7±65.0 °C(predicted)
• 密度：
  1.43±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (19S)-10,19-diethyl-7,19-dihydroxy-8-prop-2-enyl-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 溶剂黄146 为溶剂， 生成 (8S)-2-(bromomethyl)-8,15-diethyl-8-hydroxy-1,8,11,14-tetrahydro-12H-furo[3,2-f]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-9,12(2H)-dione
  参考文献：
  名称：

  Synthesis and antitumor activity of the hexacyclic camptothecin derivatives

  摘要：

  A series of hexacyclic camptothecin derivatives were synthesized to test for antitumor activity as topoisomerase I inhibitor. The strategy of synthesis was used for the formation of additional furan and dihydrofuran rings fused with 9- and 10-positions of camptothecin. All of the hexacyclic camptothecins were assayed for cytotoxicity against four human tumor cell lines, HL60, BEL-7402, HCT-116, and HeLa, and showed very impressive cytotoxicity activity in vitro. Enzyme activity of the hexacyclic camptothecins was evaluated, being equal or superior to that of SN-38. The stability of four compounds was assessed in human plasma. Two of these compounds were chosen to test for antitumor activity in vivo against Sarcoma-180. The results suggested that additional furan and dihydrofuran rings could improve the antitumor activity in vitro and vivo, though the stability of the lactone ring did not increase. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.063
• 作为产物：
  描述：

  7-乙基-10-羟基喜树碱 在 potassium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (19S)-10,19-diethyl-7,19-dihydroxy-8-prop-2-enyl-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
  参考文献：
  名称：

  喜树碱的7-乙基-9-烷基衍生物的合成及抗肿瘤活性。

  摘要：

  合成了一系列新的喜树碱衍生物，作为拓扑异构酶I抑制剂，以鉴定有效的抗肿瘤药。合成方法基于10-烯丙氧基-7-乙基喜树碱的Claisen重排。测定所有化合物对两种人类肿瘤细胞系Bel7402，HCT116的细胞毒性，并在体外显示出良好的效价。评估化合物2、4、9在人血浆中内酯的稳定性。然后测试化合物2在体外对小鼠肿瘤肉瘤180的抗肿瘤活性。结果表明，喜树碱的7位和9位上的小烷基基团在体内和体外均可促进脂溶性和抗肿瘤活性，尽管并没有增加内酯的稳定性。

  DOI：

  10.1016/j.bmcl.2005.02.072