3'-dephenyl-3'-(2-methyl-1-propenyl)-10-acetyldocetaxel | 158976-49-9

• 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
• 英文名称: 3'-dephenyl-3'-(2-methyl-1-propenyl)-10-acetyldocetaxel
• 英文别名: 10-acetyl-3'-dephenyl-3'-(2-methyl-1-propenyl)docetaxel；SB-T-1102；10-acetyl-3'-dephenyl-3'-(2-methyl-2-propenyl)docetaxel；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-1,9-dihydroxy-15-[(2R,3S)-2-hydroxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoyl]oxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 158976-49-9
• 化学式: C₄₃H₅₇NO₁₅
• 分子量: 827.923
• InChiKey: NRISGROGJFACOP-LYEXFJIESA-N

物化性质

• 熔点：
  157-160 °C
• 沸点：
  873.2±65.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  59
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  231
• 氢给体数：
  4
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  3'-dephenyl-3'-(2-methyl-1-propenyl)-10-acetyldocetaxel 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 24.0h， 以85%的产率得到10-acetyl-3'-dephenyl-3'-(2-methylpropyl)docetaxel
  参考文献：
  名称：

  Syntheses and Structure−Activity Relationships of the Second-Generation Antitumor Taxoids:  Exceptional Activity against Drug-Resistant Cancer Cells

  摘要：

  A series of new 3'-(2-methyl-1-propenyl) and 3'-(2-methylpropyl) taxoids with modifications at C-10 was synthesized by means of the beta-lactam synthon method using 10-modified 7-(triethylsilyl)-10-deacetylbaccatin III derivatives. The new taxoids thus synthesized show excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon (HT-29), and breast (MCF-7) cancer cell lines. All but one of these new taxoids possess better activity than paclitaxel and docetaxel in the same assay, i.e., the IC50 values of almost all the taxoids are in the subnanomolar level. It is found that a variety of modifications at C-10 is tolerated for the activity against normal cancer cell lines, but the activity against a drug-resistant human breast cancer cell line expressing MDR phenotype (MCF7-R) is highly dependent on the structure of the C-10 modifier. A number of the new taxoids exhibit remarkable activity (IC50 = 2.1-9.1 nM) against MCF7-R. Among these, three new taxoids, SB-T-1213 (4a), SB-T-1214 (4b), and SB-T-1102 (5a), are found to be exceptionally potent, possessing 2 orders of magnitude better activity than paclitaxel and docetaxel. The observed exceptional activity of these taxoids may well be ascribed to an effective inhibition of P-glycoprotein binding by the modified C-10 moieties. The new taxoid SB-T-1213 (4a) shows an excellent activity (T/C = 0% at 12.4 and 7.7 mg/kg/dose, log(10) cell kill = 2.3 and 2.0, respectively) against B16 melanoma in B6D2F(1) mice via intravenous administration.

  DOI：

  10.1021/jm9604080
• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 在 吡啶 、 咪唑 、 氢氟酸 、 sodium hexamethyldisilazane 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.5h， 生成 3'-dephenyl-3'-(2-methyl-1-propenyl)-10-acetyldocetaxel
  参考文献：
  名称：

  Structure–activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells

  摘要：

  A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mphi. Positions G-3' and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN M and the cytotoxicity against Mphi-like cells. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00181-0

文献信息

• POLYMORPHS OF N-MALONYL-BIS(N`-METHYL-N`-THIOBENZOYLHYDRAZIDE)
  申请人：SYNTA PHARMACEUTICALS CORP.

  公开号：US20140350115A1

  公开（公告）日：2014-11-27

  At least 70% by weight of Compound 1 is the single crystalline form, Form A, Form C, or Form D, of the compound. A pharmaceutical composition comprises a pharmaceutically acceptable carrier or diluent, and compound 1, wherein at least 70% by weight of the compound is the single crystalline form, Form A, Form C, or Form D, of the compound. A method of treating a subject with cancer comprises administering to the subject an effective amount of compound 1 or the pharmaceutical composition.

  化合物1的重量至少70％是化合物的单晶形式，即A型、C型或D型。一种药物组合物包括一种药学上可接受的载体或稀释剂，以及化合物1，其中至少70％的化合物是单晶形式，即A型、C型或D型。一种治疗癌症患者的方法包括向患者投予化合物1或药物组合物的有效量。
• 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。
• 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。
• Bis(thiohydrazide amides) formulation
  申请人：Koya Keizo

  公开号：US20080118562A1

  公开（公告）日：2008-05-22

  Disclosed herein are compositions and methods useful for the in vivo delivery bis(thiohydrazide amides), encased in a polymeric biocompatible shell.
• Combination with Bis(thiohydrazide amides) for treating cancer
  申请人：Koya Keizo

  公开号：US20080119440A1

  公开（公告）日：2008-05-22

  Disclosed herein are methods of treating a proliferative disease, such as cancer, with bis(thio-hydrazide amides) or a tautomer, pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, in combination with hyperthermia treatment. Also disclosed are methods of treating a proliferative disease, such as cancer, with bis(thio-hydrazide amides) or a tautomer, pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, in combination with radiotherapy.