7-(2-aminoethoxy)iminomethylcamptothecin

• 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: 7-(2-aminoethoxy)iminomethylcamptothecin
• 英文别名: ST1968；7-[(2-amino)ethoxyiminomethyl]-20S-camptothecin；namitecan；(19S)-10-(2-aminoethoxyiminomethyl)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione
• 化学式: C₂₃H₂₂N₄O₅
• 分子量: 434.451
• InChiKey: IBTISPLPBBHVSU-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  、 7-(2-aminoethoxy)iminomethylcamptothecin 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Novel tumor-targeted RGD peptide–camptothecin conjugates: Synthesis and biological evaluation

  摘要：

  Five RGD peptide-camptothecin (CPT) conjugates were designed and synthesized with the purpose to improve the therapeutic index of this antitumoral drug family. New RGD cyclopeptides were selected on the basis of their high affinity to alpha(v) integrin receptors overexpressed by tumor cells and their metabolic stability. The conjugates can be divided in two groups: in the first the peptide was attached to the drug through an amide bond, in the second through a hydrazone bond. The main difference between the two spacers lies in their acid stability. Affinity to the receptors was maintained for all conjugates and their internalization into tumor cells was demonstrated. The first group conjugates showed lower in vitro and in vivo activity than the parent drug, probably due to the excessive stability of the amide bond, even inside the tumor cells. Conversely, the hydrazone conjugates exhibited in vitro tumor cell inhibition similar to the parent drug, indicating high conversion in the culture medium and/or inside the cells, but their poor solubility hampered in vivo experiments. On the basis of these results, information was acquired for additional development of derivatives with different linkers and better solubility for in vivo evaluation. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.019
• 作为产物：
  描述：

  2-aminoethoxyamine dihydrochloride 、 (S)-11-formy-4-乙基-4-羟基-1,12-二氢-4H-2-噁-6,12a-二氮杂-二苯并b,h芴-3,13-二酮 生成 7-(2-aminoethoxy)iminomethylcamptothecin
  参考文献：
  名称：

  Camptothecin derivatives having antitumor activity

  摘要：

  本文披露了公式（I）的喜树碱衍生物，其中R1、R2和R3基团的定义如描述中所述。公式（I）化合物具有抗肿瘤活性，并显示出良好的治疗指数。本文还披露了公式（I）化合物的制备过程以及它们在制备用于治疗肿瘤、病毒感染和疟原虫的药物中的应用。

  公开号：

  US06242457B1

文献信息

• Camptothecin derivatives having antitumor activity
  申请人：Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.

  公开号：US06242457B1

  公开（公告）日：2001-06-05

  Camptothecin derivatives of camptothecin of formula (I) wherein the groups R1, R2 and R3 are as defined in the description are disclosed. The compounds of formula (I) are endowed with antitumor activity and show a good therapeutic index. Processes for the preparation of the compounds of formula (I) and their use in the preparation of medicaments useful in the treatment of tumors, viral infections and antiplasmodium falciparum are also disclosed.

  本文披露了公式（I）的喜树碱衍生物，其中R1、R2和R3基团的定义如描述中所述。公式（I）化合物具有抗肿瘤活性，并显示出良好的治疗指数。本文还披露了公式（I）化合物的制备过程以及它们在制备用于治疗肿瘤、病毒感染和疟原虫的药物中的应用。
• Synthesis and DNA-cleaving activity of lactenediynes conjugated with DNA-complexing moieties
  作者：Luca Banfi、Andrea Basso、Elisabetta Bevilacqua、Valentina Gandolfo、Giuseppe Giannini、Giuseppe Guanti、Loana Musso、Monica Paravidino、Renata Riva

  DOI：10.1016/j.bmc.2008.02.022

  日期：2008.4.1

  Lactenediynes are compounds characterized by the fusion of a beta-lactam with a cyclodeca-3-ene-1,5-diyne. In this work the most promising members of this family have been activated by attaching a carbalkoxy or a carbamoyl group to the azetidinone nitrogen, and conjugated to various DNA-complexing moieties, either acting by intercalation or through groove binding. These conjugated artificial enediynes have been demonstrated to possess in vitro ability to produce single and double strand cleavage of plasmid DNA. As potency and capacity to induce double cut, they rank among the best simple enediyne analogues ever prepared. A thorough investigation was carried out in order to develop the best suited linkers for assembling these conjugates. (C) 2008 Elsevier Ltd. All rights reserved.
• Novel tumor-targeted RGD peptide–camptothecin conjugates: Synthesis and biological evaluation
  作者：Alma Dal Pozzo、Ming-Hong Ni、Emiliano Esposito、Sabrina Dallavalle、Loana Musso、Alberto Bargiotti、Claudio Pisano、Loredana Vesci、Federica Bucci、Massimo Castorina、Rosanna Foderà、Giuseppe Giannini、Concetta Aulicino、Sergio Penco

  DOI：10.1016/j.bmc.2009.11.019

  日期：2010.1

  Five RGD peptide-camptothecin (CPT) conjugates were designed and synthesized with the purpose to improve the therapeutic index of this antitumoral drug family. New RGD cyclopeptides were selected on the basis of their high affinity to alpha(v) integrin receptors overexpressed by tumor cells and their metabolic stability. The conjugates can be divided in two groups: in the first the peptide was attached to the drug through an amide bond, in the second through a hydrazone bond. The main difference between the two spacers lies in their acid stability. Affinity to the receptors was maintained for all conjugates and their internalization into tumor cells was demonstrated. The first group conjugates showed lower in vitro and in vivo activity than the parent drug, probably due to the excessive stability of the amide bond, even inside the tumor cells. Conversely, the hydrazone conjugates exhibited in vitro tumor cell inhibition similar to the parent drug, indicating high conversion in the culture medium and/or inside the cells, but their poor solubility hampered in vivo experiments. On the basis of these results, information was acquired for additional development of derivatives with different linkers and better solubility for in vivo evaluation. (C) 2009 Elsevier Ltd. All rights reserved.