9-nitrocamptothecin-20-O-butyrate

• 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: 9-nitrocamptothecin-20-O-butyrate
• 英文别名: [(19S)-19-ethyl-8-nitro-14,18-dioxo-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)-heptaen-19-yl] butanoate
• 化学式: C₂₄H₂₁N₃O₇
• 分子量: 463.447
• InChiKey: SPLFBXLHYCYRJP-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  132
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  丁酸酐 、 鲁比替康 在 吡啶 作用下， 以56%的产率得到9-nitrocamptothecin-20-O-butyrate
  参考文献：
  名称：

  Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs

  摘要：

  通用公式所代表的紫杉醇衍生物如下所述： 其中当R1为H时，R为C2-C4烷基、C6-C15烷基、C3-C8环烷基、C2-C15烯基或C2-C15环氧基；当R2为硝基或氨基时，R1为C1-C15烷基、C1-C15烯基、C3-C8环烷基或环氧基。还描述了包括这些特定紫杉醇衍生物的脂质体前药，其受限于脂质体传递系统。还公开了制备这些前药以及在癌症治疗中使用它们的方法。

  公开号：

  US06352996B1

文献信息

• Alkyl Esters of Camptothecin and 9-Nitrocamptothecin:  Synthesis, in Vitro Pharmacokinetics, Toxicity, and Antitumor Activity
  作者：Zhisong Cao、Nick Harris、Anthony Kozielski、Dana Vardeman、John S. Stehlin、Beppino Giovanella

  DOI：10.1021/jm9607562

  日期：1998.1.1

  Eleven camptothecin esters, 6a-e and 7a-f, were prepared by straightforward acylation of camptothecins with the corresponding acylating reagents such as organic anhydrides and carboxylic acid chlorides. The in vitro pharmacokinetic determination of lactone levels of esters 6a and 7b showed that the biological life span of their lactone forms in human and mouse plasma significantly increased when compared with their mother compounds, camptothecin (3) and 9-nitrocamptothecin (4). The differences of lactone levels between human plasma and mouse plasma for 6a and 7b were much smaller than what was observed for their mother compounds. The in vivo antitumor activity and toxicity studies demonstrated that some of these esters were very active against human tumor xenografts in nude mice and had an exceptional lack of toxicity in nude mice, even at enormous doses.