7-((甲硫基)甲基)紫杉醇 | 160237-25-2

• 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: 7-((甲硫基)甲基)紫杉醇
• 英文名称: BMS-184476
• 英文别名: 7-((methylthio)methyl)paclitaxel；7-Methylthiomethylpaclitaxel；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-9-(methylsulfanylmethoxy)-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 160237-25-2
• 化学式: C₄₉H₅₅NO₁₄S
• 分子量: 914.04
• InChiKey: UBJAHGAUPNGZFF-XOVTVWCYSA-N

物化性质

• 沸点：
  975.5±65.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  65
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  236
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  7-((甲硫基)甲基)紫杉醇 在 palladium on activated charcoal N-碘代丁二酰亚胺 、 4 A molecular sieve 、 氢气 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 25.0~37.0 ℃ 、413.69 kPa 条件下， 反应 2.5h， 生成 紫杉醇
  参考文献：
  名称：

  Synthesis and antitumor evaluation of paclitaxel phosphonooxymethyl ethers: a novel class of water soluble paclitaxel pro-drugs

  摘要：

  The synthesis, pharmacokinetic properties, and antitumor evaluation of novel paclitaxel phosphonooxymethyl ether derivatives 8-11 and salts thereof is described. These compounds exhibit improved water solubility as compared to paclitaxel (1) and upon incubation with plasma and alkaline phosphatase they readily release parent drug. The in vivo antitumor evaluation of compounds 8-11 established them as suitable pro-drugs of paclitaxel. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00321-6
• 作为产物：
  描述：

  紫杉醇 在 吡啶 、 盐酸 、 过氧化苯甲酰 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 3.5h， 生成 7-((甲硫基)甲基)紫杉醇
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Novel C-7 Paclitaxel Ethers:  Discovery of BMS-184476

  摘要：

  The preparation of C-7 paclitaxel ethers is described. Various substituted ethers were prepared via activation of the corresponding methylthiomethyl ether followed by alcohol addition. Variation of the C-7 ether group as well the 3' side chain position led to the discovery of a novel taxane, BMS-184476 (4), with preclinical antitumor activity superior to paclitaxel.

  DOI：

  10.1021/jm0102607

文献信息

• Paclitaxel enhancer compounds
  申请人：Koya Keizo

  公开号：US20080214655A1

  公开（公告）日：2008-09-04

  Disclosed is a compound represented by the Structural Formula (I): Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R 7 R 8 )—. R 1 and R 2 are independently an aryl group or a substituted aryl group, R 3 and R 4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 5 -R 6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 7 and R 8 are each independently —H, an aliphatic or substituted aliphatic group, or R 7 is —H and R 8 is a substituted or unsubstituted aryl group, or, R 7 and R 8 , taken together, are a C2-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject with cancer by administering to the subject a compound of Structural Formula (I) in combination with Paclitaxel or an analog of Paclitaxel.

  本发明揭示了一种由结构式（I）表示的化合物： 其中，Y是共价键，苯基或取代或未取代的直链烃基团。此外，Y与其连接的两个>C=Z基团一起，是取代或未取代的芳香族基团。优选地，Y是共价键或—C（R7R8）—。R1和R2分别是芳基基团或取代芳基基团，R3和R4分别是—H、脂肪基、取代脂肪基、芳基或取代芳基。R5-R6分别是—H、脂肪基、取代脂肪基、芳基或取代芳基。R7和R8各自独立地是—H、脂肪基或取代脂肪基，或者R7是—H，R8是取代或未取代的芳基基团，或者R7和R8一起是C2-C6取代或未取代的烷基基团。Z是═O或═S。本发明还揭示了包含本发明化合物和药学可接受的载体或稀释剂的制药组合物。本发明还揭示了一种通过将Paclitaxel或Paclitaxel类似物与结构式（I）的化合物联合给予受试者治疗癌症的方法。
• COMPOUNDS FOR TREATING PROLIFERATIVE DISORDERS
  申请人：Koya Keizo

  公开号：US20140031429A1

  公开（公告）日：2014-01-30

  Disclosed are compounds and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and/or natural killer induction. Also, disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier.

  本发明涉及化合物及其使用方法，用于治疗具有增殖性疾病的受试者，例如癌症，并且用于治疗对Hsp70诱导和/或自然杀伤细胞诱导有反应的疾病的方法。此外，本发明还涉及包含本发明化合物和药用可接受载体的制药组合物。
• 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。
• Enhanced loading of intact, bacterially derived vesicles with small molecule compounds
  申请人：EnGeneIC Molecular Delivery Pty Ltd

  公开号：US11052157B2

  公开（公告）日：2021-07-06

  Enhanced loading of small molecule compounds into intact, bacterially derived vesicles provides operational and therapeutic advantages.

  将小分子化合物装载到完整的细菌衍生囊泡中，可增强操作和治疗优势。
• Bioorganic amp; Medicinal Chemistry Letters 1996, 6, 1837-1842
  作者：

  DOI：——

  日期：——