2'-O-甲基紫杉醇 | 156413-67-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 2'-O-甲基紫杉醇
• 英文名称: 2'-methoxypaclitaxel
• 英文别名: 2'-O-Methyl Paclitaxel；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-methoxy-3-phenylpropanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 156413-67-1
• 化学式: C₄₈H₅₃NO₁₄
• 分子量: 867.947
• InChiKey: CXXNFHTXDMZRLB-JBTWBBNCSA-N

物化性质

• 熔点：
  195-210°C
• 溶解度：
  可溶于二甲基亚砜、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  63
• 可旋转键数：
  15
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  210
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  紫杉醇 、 碘甲烷 在 silver(l) oxide 作用下， 以 丙酮 为溶剂， 反应 168.0h， 以44%的产率得到2'-O-甲基紫杉醇
  参考文献：
  名称：

  Conformational Studies of Paclitaxel Analogs Modified at the C-2‘ Position in Hydrophobic and Hydrophilic Solvent Systems

  摘要：

  The conformations of two paclitaxel analogs modified at the C-2' position, 2'-deoxypaclitaxel and 2'-methoxypaclitaxel, were studied in hydrophobic Emd hydrophilic solvent systems by a combination of NMR spectroscopy, CD measurements, and molecular modeling. Both analogs have hydrophobic and hydrophilic conformations that resemble those of paclitaxel itself in the same media. Since the two have diminished biological activities in a number of bioactivity assays and the hydrogen-bonding capability of the 2'-hydroxyl group has been eliminated, we postulate that this group is involved in hydrogen bonding with tubulin and plays an important role in molecular recognition. The results of this study are in agreement with our earlier report on paclitaxel 2'-acetate, an analog in which the 2'-hydroxyl group hydrogen-bonding capacity has also been eliminated.

  DOI：

  10.1021/jm970026+

文献信息

• [EN] FATTY ACID ANTICANCER DERIVATIVES AND THEIR USES<br/>[FR] DÉRIVÉS D'ACIDES GRAS ANTI-CANCÉREUX ET LEURS UTILISATIONS
  申请人：CATABASIS PHARMACEUTICALS INC

  公开号：WO2014204856A1

  公开（公告）日：2014-12-24

  The invention relates to fatty acid anticancer derivatives; compositions comprising an effective amount of a fatty acid anticancer derivative; and methods for treating or preventing cancer comprising the administration of an effective amount of a fatty acid anticancer derivative.

  这项发明涉及脂肪酸抗癌衍生物；包含有效量脂肪酸抗癌衍生物的组合物；以及治疗或预防癌症的方法，包括给予有效量脂肪酸抗癌衍生物的管理。
• [EN] TRIGGER-ACTIVATABLE METABOLIC SUGAR PRECURSORS FOR CANCER-SELECTIVE LABELING AND TARGETING<br/>[FR] PRÉCURSEURS MÉTABOLIQUES DE SUCRE, ACTIVABLES PAR UN DÉCLENCHEUR POUR LE MARQUAGE ET LE CIBLAGE SÉLECTIF D'UN CANCER
  申请人：UNIV ILLINOIS

  公开号：WO2017062800A1

  公开（公告）日：2017-04-13

  Disclosed are compounds for the selective labeling of cell-surface sugars in cancer cells. The compounds are activatable by triggers specific to cancer cells, and, when metabolized, label a cancer cell surface sugar with an azide chemical group. Facilitated by a click chemistry reaction, combination of the cell surface-expressed azide with a alkynyl- drug conjugate enables efficient targeted drug delivery to cancer cells with reduced toxicity Also disclosed are compounds for delivering a drug to an azide-bearing cancer cell, and methods of treating cancer using the compounds of the invention.

  本文披露了一种用于选择性标记癌细胞表面糖分子的化合物。这些化合物可被癌细胞特异性触发器激活，并在代谢时，使用偶氮化学基标记癌细胞表面的糖分子。通过点击化学反应，将表面表达偶氮基的细胞与烷基-药物结合物结合，可以实现高效的靶向药物传递至癌细胞，同时减少毒性。此外，本文还披露了一种将药物传递至带有偶氮基的癌细胞的化合物，以及使用本发明的化合物治疗癌症的方法。
• [EN] METHODS OF USING MODIFIED CYTOTOXINS TO TREAT CANCER<br/>[FR] PROCÉDÉS D'UTILISATION DE CYTOTOXINES MODIFIÉES POUR TRAITER LE CANCER
  申请人：UNIV NORTHWESTERN

  公开号：WO2021007322A1

  公开（公告）日：2021-01-14

  The present disclosure provides methods of using prodrugs of small-molecule cytotoxins for the treatment of cancer. In some embodiments, the cancer is a tumor comprising cells that overexpress fatty acid uptake proteins, such as cells that overexpress fatty acid translocase CD36. In some other aspects, the disclosure provides compositions suitable for use in such methods. In some further aspects, the disclosure provides combination therapies that may be suitable used in combination with the use of small-molecule prodrugs disclosed herein.

  本公开提供了使用小分子细胞毒素的前药治疗癌症的方法。在一些实施例中，癌症是包含过度表达脂肪酸摄取蛋白的细胞的肿瘤，例如过度表达脂肪酸转运酶CD36的细胞。在其他一些方面，本公开提供了适用于此类方法的组合物。在进一步的一些方面，本公开提供了可能适用于与本公开所披露的小分子前药的使用相结合的组合治疗方法。
• Bis(thio-hydrazide amide) salts for treatment of cancers
  申请人：Synta Pharmaceuticals Corp.

  公开号：EP2305642A2

  公开（公告）日：2011-04-06

  Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I)          2 M+ or M2+Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently -H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is -O or -S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation. Also disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt.

  所公开的是双(硫代酰肼酰胺)二盐，其结构式为 (I) 2 M+ 或 M2+Y 是共价键或取代或未取代的直链烃基。R1-R4 独立地为-H、脂肪族基团、取代的脂肪族基团、芳基或取代的芳基，或 R1 和 R3 与它们所键合的碳原子和氮原子，和/或 R2 和 R4 与它们所键合的碳原子和氮原子，形成一个可选择与芳香环融合的非芳香杂环。Z 是-O 或-S。M+ 是药学上可接受的一价阳离子，M2+ 是药学上可接受的二价阳离子。还公开了包含上述双（硫肼酰胺）二盐的药物组合物。进一步公开了治疗癌症患者的方法。这些方法包括给药有效量的双(硫代酰肼酰胺)二盐的步骤。
• Modified cytotoxins and their therapeutic use
  申请人：The Regents of the University of California

  公开号：US10286079B2

  公开（公告）日：2019-05-14

  The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides small-molecule cytotoxins that are chemically modified to include one or more moieties that include hydrophobic portions. In some embodiments, the disclosure provides small-molecule cytotoxins that are chemically modified with fatty acid-containing moieties. In some aspects, the disclosure provides compositions, such as pharmaceutical compositions, that include such modified small-molecule cytotoxins and a protein. In some embodiments, the protein is albumin or an albumin mimetic. Further, the disclosure provides various uses of these compounds and compositions.

  本公开内容一般提供用于治疗癌症的化合物。在某些方面，本公开提供的小分子细胞毒素经过化学修饰，包括一个或多个含有疏水部分的分子。在一些实施方案中，本公开提供了用含脂肪酸的分子进行化学修饰的小分子细胞毒素。在某些方面，本公开提供的组合物，如药物组合物，包括这种修饰的小分子细胞毒素和蛋白质。在某些实施方案中，蛋白质是白蛋白或白蛋白模拟物。此外，本公开还提供了这些化合物和组合物的各种用途。