(2S)-2-[1-(二甲基氨基甲基)-2-羟基-8-(羟基甲基)-9-氧代-11H-吲哚嗪并[1,2-b]喹啉-7-基]-2-羟基丁酸 | 132877-29-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 中文名称: (2S)-2-[1-(二甲基氨基甲基)-2-羟基-8-(羟基甲基)-9-氧代-11H-吲哚嗪并[1,2-b]喹啉-7-基]-2-羟基丁酸
• 英文名称: Topotecan hydroxyl acid
• 英文别名: topotecan；(2S)-2-[1-[(dimethylazaniumyl)methyl]-2-hydroxy-8-(hydroxymethyl)-9-oxo-11H-indolizino[1,2-b]quinolin-7-yl]-2-hydroxybutanoate
• CAS: 132877-29-3
• 化学式: C₂₃H₂₅N₃O₆
• 分子量: 439.468
• InChiKey: DPQJTQJZJNYUEC-QHCPKHFHSA-N

物化性质

• 沸点：
  804.3±65.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  拓扑替康 在 poly(DL-lactide-co-glycolide) 、 poly(vinyl alcohol) 作用下， 以 various solvents 为溶剂， 反应 192.0h， 生成 (2S)-2-[1-(二甲基氨基甲基)-2-羟基-8-(羟基甲基)-9-氧代-11H-吲哚嗪并[1,2-b]喹啉-7-基]-2-羟基丁酸
  参考文献：
  名称：

  摘要：

  Purpose. The camptothecin (CPT) analogue, 10-hydroxycamptothecin (10-HCPT) has been shown previously to remain in its acid-stable land active) lactone form when encapsulated in poly(lactide-co-glycolide) (PLGA) microspheres (1). The purpose of this study was to determine the principal mechanism(s) of 10-HCPT stabilization.Methods. CPTs were encapsulated in PLGA 50:50 microspheres by standard solvent evaporation techniques. Microspheres were eroded in pH 7.4 buffer at 37 degrees C. The ratio of encapsulated lactone to carboxylate was determined by HPLC as a function of time, initial form of drug encapsulated, fraction of co-encapsulated Mg(OH)(2), CPT lipophilicity, and drug loading. Two techniques were developed to assess the microclimate pH, including: i) measurement of H+ content of the dissolved microspheres in an 80:20 acetonitrile/H2O mixture and iii confocal microscopy of an encapsulated pH-sensitive dye, fluorescein.Results. The encapsulated carboxylate converted rapidly to the lactone after exposure to the release media, indicating the lactone is favored at equilibrium in the microspheres. Upon co-encapsulation of Mg(OH)(2), the trend was reversed, i.e., the lactone rapidly converted to the carboxylate form. Measurement of -log(hydronium ion activity) (pa(H)*) of dissolved microspheres with pH-electrode and pH mapping with fluorescein revealed the presence of an acidic microclimate. From the measurements of H+ and water contents of particles hydrated for 3 days, a microclimate pH was estimated to be in the neighborhood of 1.8. The co-encapsulation of Mg(OH)(2) could both increase the pa(H)* reading and neutralize pH in various regions of the microsphere interior. Varying the drug lipophilicity and loading revealed that the precipitation of the lactone could also stabilize CPT.Conclusions, PLGA microspheres prepared by the standard solvent evaporation techniques develop an acidic microclimate that stabilizes the lactone form of CPTs. This microclimate may be neutralized by co-encapsulating a base such as Mg(OH)(2), as suggested by previous work with poly(ortho eaters) (2).

  DOI：

  10.1023/a:1018876308346

文献信息

• PROCESS FOR PREPARING TOPOTECAN
  申请人：Palle Acharyulu Venkata Raghavendra

  公开号：US20070149783A1

  公开（公告）日：2007-06-28

  A process for preparing topotecan.

  制备托泊替康的过程。
• Water-Soluble Polymer Conjugates of Topotecan
  申请人：Gu Xuyuan

  公开号：US20140371258A1

  公开（公告）日：2014-12-18

  Provided herein are water-soluble polymer conjugates of topotecan, along with compositions comprising the conjugates and related methods of making and using the same.

  本文提供了水溶性聚合物结合拓扑替康的化合物，以及包含这些结合物的组合物和相关的制备和使用方法。
• DNA Interactions of Two Clinical Camptothecin Drugs Stabilize Their Active Lactone Forms
  作者：Danzhou Yang、J. Thompson Strode、H. Peter Spielmann、Andrew H.-J. Wang、Thomas G. Burke

  DOI：10.1021/ja973433j

  日期：1998.4.1
• Supramolecular Diversity through Click Chemistry: Switching from Nanomicelles to 1D-Nanotubes and Tridimensional Hydrogels
  作者：Mohyeddin Assali、Juan-José Cid、Inmaculada Fernández、Noureddine Khiar

  DOI：10.1021/cm4022613

  日期：2013.11.12

  The size and shape of nanoparticles are of prominent importance for their biological activities and for their application as smart drug delivery systems. Thus, synthetic designs allowing divergent synthesis of nanoscale materials with controlled size, morphology, and surface chemistry are currently highly desirable, but they remain a major challenge. Herein, we report a simple method for the creation of supramolecular diversity from structurally related diacetylenic-based glycolipids. We have found that neoglycolipids with an amide function between the hydrophilic and hydrophobic part of the amphiphile afford tridimensional micelles, while those having a triazole self-organize into 1D-nanotubes. Additionally, at higher concentrations, the clicked amphiphiles form hydrogels through three-dimensional networks of bundled nanotubes. Photopolymerization of the obtained nanomaterials leads to the formation of conjugated polydiacetylene backbone of alternating enyne groups, which rigidify glyconanomaterial structures enhancing their physical stability. The obtained nanostructures were extensively characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) techniques, enabling the confirmation of the formation of tubular structures in water for all triazolo-substituted neoglycolipids and micellar structures for the glycolipid containing an amide group. This fact refutes the so-called isosteric character of 1,2,3-triazole and amide groups, at least, at the supramolecular level and point out to the possibility of using the CuAAC between azides and alkynes to create supramolecular diversity at the nanoscale. The functionality of the gel was, moreover, evaluated as a nanocontainer for the incarceration and controlled release of the antitumoral topotecan.
• US7547785B2
  申请人：——

  公开号：US7547785B2

  公开（公告）日：2009-06-16