10-hydroxyl-9-L-prolinol (+)methylcamptothecin | 1439356-77-0

• 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-hydroxyl-9-L-prolinol (+)methylcamptothecin
• 英文别名: (19S)-19-ethyl-7,19-dihydroxy-8-[[(2S)-2-(hydroxymethyl)pyrrolidin-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: 1439356-77-0
• 化学式: C₂₆H₂₇N₃O₆
• 分子量: 477.517
• InChiKey: DYRKSLHHIBGLAO-HAWMADMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  10-hydroxyl-9-L-prolinol (+)methylcamptothecin 在 sodium hypochlorite 作用下， 以92.1%的产率得到ortho-quinonemethide
  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
• 作为产物：
  描述：

  聚合甲醛 、 10-羟基喜树碱 、 L-脯氨醇 以 溶剂黄146 为溶剂， 以90.2%的产率得到10-hydroxyl-9-L-prolinol (+)methylcamptothecin
  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

文献信息

• Cyclane-aminol 10-hydroxycamptothecin analogs as novel DNA topoisomerase I inhibitors induce apoptosis selectively in tumor cells
  作者：Shixuan Zhang、Tao Geng、Bo Jiang、Ge Song、Lisha Ha、Chenguang Sun、Yuan Qian、Qingyu Fan、Hongmin Guo

  DOI：10.1097/cad.0000000000000083

  日期：2014.7

  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.