10-hydroxy-9-[(4'-hydroxyethyl)piperazin-1-ylmethyl]camptothecin | 1439356-85-0

• 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: 10-hydroxy-9-[(4'-hydroxyethyl)piperazin-1-ylmethyl]camptothecin
• 英文别名: (19S)-19-ethyl-7,19-dihydroxy-8-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-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: 1439356-85-0
• 化学式: C₂₇H₃₀N₄O₆
• 分子量: 506.558
• InChiKey: MJVBESTVJNHODP-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-羟乙基哌嗪 、 聚合甲醛 、 10-羟基喜树碱 以 溶剂黄146 为溶剂， 以70.1%的产率得到10-hydroxy-9-[(4'-hydroxyethyl)piperazin-1-ylmethyl]camptothecin
  参考文献：
  名称：

  Cyclane-aminol 10-hydroxycamptothecin analogs as novel DNA topoisomerase I inhibitors induce apoptosis selectively in tumor cells

  摘要：

  A novel series of cyclane-aminol 10-hydroxycamptothecin (HCPT) analogs was designed and synthesized through the Mannich reaction using HCPT as the lead compound, such as 10-hydroxyl-9-L-prolinol (+) methylcamptothecin (PRPT), 10-hydroxyl-9-(4'-hydroxy) piperidinylmethylcamptothecin (PPPT), and 10-hydroxy-9(4'-hydroxyethyl)-piperazinylmethycamptothecin (QPPT). Three kinds of new cyclane-aminols were introduced into the structure of HCPT, which modified strong cytotoxic HCPT into cyclane-aminol HCPT analogs with moderate cytotoxicity and improved selectivity toward DNA topoisomerase I inhibition in tumor cells. Special metabolic pathways for cyclane-aminol HCPT analogs in rats were discovered, which differed from other HCPT analogs. Cyclane-aminol HCPT analogs can capture O-2(-) and cause an increase in intracellular hydrogen peroxide levels with selective induction of apoptosis in tumor cells rather than in normal peripheral blood mononuclear cells. Among them, PPPT has a much better druggability than topotecan (TPT) and has the potential to be developed into an antitumor agent. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

  DOI：

  10.1097/cad.0000000000000083