gimatecan | 292620-90-7

• 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: gimatecan
• 英文别名: [3H]-Gimatecan；7-tert-Butoxyiminomethylcamptothecin；(19S)-19-ethyl-19-hydroxy-10-[(2-methylpropan-2-yl)oxyiminomethyl]-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
• CAS: 292620-90-7
• 化学式: C₂₅H₂₅N₃O₅
• 分子量: 447.491
• InChiKey: UIVFUQKYVFCEKJ-VWLOTQADSA-N

物化性质

• 熔点：
  250 °C (decomp)
• 沸点：
  780.6±70.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  gimatecan 在 4-二甲氨基吡啶 、 甲酸 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 ST8161AA1
  参考文献：
  名称：

  Growth inhibition of human ovarian carcinoma by a novel AvidinOX-anchored biotinylated camptothecin derivative

  摘要：

  Oxidized form of avidin, named AvidinOX, provides stable fixation of biotinylated molecules in tissues thus representing a breakthrough in topical treatment of cancer. AvidinOX proved to be a stable receptor for radiolabeled biotin, biotinylated antibodies and cells. In order to expand applicability of the AvidinOX-based delivery platform, in the present study we investigated the possibility to hold biotinylated chemotherapeutics in AvidinOX-treated sites. A novel biotinylated gimatecan-derived camptothecin, coded ST8161AA1, was injected at suboptimal doses into human tumors xenografted in mice alone or pre-complexed to AvidinOX. Significantly higher growth inhibition was observed when the drug was anchored to AvidinOX suggesting the potential utility of this delivery modality for the local treatment of inoperable tumors.

  DOI：

  10.1016/j.bmcl.2018.09.017
• 作为产物：
  描述：

  O-叔丁基羟胺盐酸盐 、 (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 以93的产率得到gimatecan
  参考文献：
  名称：

  STEREOSELECTIVE PROCESS AND CRYSTALLINE FORMS OF A CAMPTOTHECIN

  摘要：

  本文披露了一种制备7-[(E)-t-丁氧基亚胺甲基]-喜树碱（也称为吉马替康）的立体选择性过程。通过在适当的不同溶剂混合物中进行进一步的溶解和沉淀步骤，使用相同的立体选择性过程也可以获得四种新的吉马替康晶体形式。

  公开号：

  US20090239893A1

文献信息

• STEREOSELECTIVE PROCESS AND CRYSTALLINE FORMS OF A CAMPTOTHECIN
  申请人：Carminati Paolo

  公开号：US20090239893A1

  公开（公告）日：2009-09-24

  A stereoselective process for preparing 7-[(E)-t-butyloxyiminomethyl]-camptothecin (also known as gimatecan) is herein disclosed. With the addition of further dissolution and precipitation steps carried out in appropriate different solvent mixtures, four new crystalline forms of gimatecan are also obtainable by using the same stereoselective process.

  本文披露了一种制备7-[(E)-t-丁氧基亚胺甲基]-喜树碱（也称为吉马替康）的立体选择性过程。通过在适当的不同溶剂混合物中进行进一步的溶解和沉淀步骤，使用相同的立体选择性过程也可以获得四种新的吉马替康晶体形式。
• Use of esters of L-carnitine or alkanoyl L-carnitines as cationic lipids for the intracellular delivery of pharmacologically active compounds
  申请人：SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A.

  公开号：EP1426044B1

  公开（公告）日：2006-02-08
• Growth inhibition of human ovarian carcinoma by a novel AvidinOX-anchored biotinylated camptothecin derivative
  作者：Olga Minenkova、Loredana Vesci、Rita De Santis、Daniela Santapaola、Raffaella Cincinelli、Loana Musso、Sabrina Dallavalle、Giuseppe Giannini

  DOI：10.1016/j.bmcl.2018.09.017

  日期：2018.11

  Oxidized form of avidin, named AvidinOX, provides stable fixation of biotinylated molecules in tissues thus representing a breakthrough in topical treatment of cancer. AvidinOX proved to be a stable receptor for radiolabeled biotin, biotinylated antibodies and cells. In order to expand applicability of the AvidinOX-based delivery platform, in the present study we investigated the possibility to hold biotinylated chemotherapeutics in AvidinOX-treated sites. A novel biotinylated gimatecan-derived camptothecin, coded ST8161AA1, was injected at suboptimal doses into human tumors xenografted in mice alone or pre-complexed to AvidinOX. Significantly higher growth inhibition was observed when the drug was anchored to AvidinOX suggesting the potential utility of this delivery modality for the local treatment of inoperable tumors.