10-cyclopropylformyl-7-triethylsilylbaccatin III | 160084-71-9

• 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: 10-cyclopropylformyl-7-triethylsilylbaccatin III
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(cyclopropanecarbonyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 160084-71-9
• 化学式: C₃₉H₅₄O₁₁Si
• 分子量: 726.937
• InChiKey: VFJIWBKUJSCHSX-PQZSINHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.07
• 重原子数：
  51
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  155
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  10-cyclopropylformyl-7-triethylsilylbaccatin III 在 palladium on activated charcoal 吡啶 、 氢氟酸 、 氢气 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， -15.0~30.0 ℃ 、101.33 kPa 条件下， 反应 29.0h， 生成 SB-T-1104
  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：

  7-O-(三乙基硅烷基)-10-去乙酰基浆果赤霉素III 生成 10-cyclopropylformyl-7-triethylsilylbaccatin III
  参考文献：
  名称：

  C10 cyclopropyl ester substituted taxane compositions

  摘要：

  在C10处具有环丙基酯基团、在C9处具有酮基团、在C7处具有羟基基团、在C3'处具有2-呋喃基团和在C3'处具有异丁氧羰基基团的紫杉醇类化合物。

  公开号：

  US20060189679A1

文献信息

• 一种含氟紫杉烷类化合物及其制备方法与应用
  申请人：牡丹江师范学院

  公开号：CN110143934B

  公开（公告）日：2023-03-28

  本发明公开了一种含氟紫杉烷类化合物及其制备方法与应用。该化合物的结构通式如式I所示。药理实验证明，本发明所合成的一系列含氟的紫杉烷类衍生物，与紫杉醇相比，对于多药耐药型人乳腺癌细胞株MCF‑7/Adr，卵巢癌细胞株NCI/Adr具有优于紫杉醇的细胞毒性，并且针对肿瘤干细胞过表达的结肠癌细胞株HCT‑116++表现出优于紫杉醇的细胞毒性。
• Synthesis and biological evaluation of novel 3′-difluorovinyl taxoids
  作者：Larissa Kuznetsova、Liang Sun、Jin Chen、Xianrui Zhao、Joshua Seitz、Manisha Das、Yuan Li、Jean M. Veith、Paula Pera、Ralph J. Bernacki、Shujun Xia、Susan B. Horwitz、Iwao Ojima

  DOI：10.1016/j.jfluchem.2012.07.007

  日期：2012.11

  3′-difluorovinyl taxoids evaluated, eight taxoids exhibited less than 100 pM IC50 values against MCF7 cell line. Difluorovinyl taxoids induced GTP-independent tubulin polymerization much faster than paclitaxel. Then, the resulting microtubules were stable to Ca2+-induced depolymerization, indicating strong stabilization of microtubules. Molecular modeling study indicated that a difluorovinyl taxoid binds to

  一系列具有 C10 修饰以及具有 C2 和 C10 修饰的 3'-二氟乙烯基紫杉醇被战略性地设计为阻断细胞色素 P-450 3A4 酶的代谢并合成。评估了这些新型二氟乙烯基紫杉素对药物敏感的人乳腺 (MCF7)、多药耐药 (MDR) 人卵巢 (NCI/ADR)、人结肠 (HT-29) 和人胰腺 (PANC-1) 癌细胞的细胞毒性线。与紫杉醇相比，3'-二氟乙烯基紫杉醇对 MCF7、HT-29 和 PANC-1 细胞系的活性高出数倍至 16 倍，对 NCI/ADR 细胞系的效力高出三个数量级。构效关系研究表明 C2 修饰对 MDR 癌细胞系的活性至关重要，而 C10 修饰对效力的影响相当小，但有一些例外。C2 修饰对 MCF7 细胞系效力的影响按以下顺序增加：H < F < Cl < N3 . 在评估的 25 种 3'-二氟乙烯基紫杉类中，8 种紫杉类对 MCF7 细胞系的pM IC 50值小于
• Synthesis of a Next-Generation Taxoid by Rapid Methylation Amenable for ¹¹C-Labeling
  作者：Joshua D. Seitz、Tao Wang、Jacob G. Vineberg、Tadashi Honda、Iwao Ojima

  DOI：10.1021/acs.joc.7b03284

  日期：2018.3.2

  synthetic route features a highly stereoselective chiral ester enolate–imine cyclocondensation, regioselective hydrostannation of the resulting β-lactam, and the Stille coupling of the novel vinylstannyl taxoid intermediate with methyl iodide. Conditions have been established to allow the rapid methylation and HPLC purification of the target compound in a time frame amenable to 11C-labeling for applications

  下一代紫杉醇，例如SB-T-1214，是高度有效的细胞毒素剂，在体内对耐药性肿瘤表现出显着的功效，包括那些过表达P-糖蛋白（Pgp）外排泵的药物。由于SB-T-1214并非Pgp介导外排的底物，因此与紫杉醇或多西他赛都是Pgp底物相比，它可能表现出明显不同的生物分布和肿瘤蓄积特征。为了使用正电子发射断层扫描（PET）研究SB-T-1214的生物分布和肿瘤蓄积水平，已开发出一种新的合成途径以允许将11种C，是在化学合成的最后一步，通过甲基碘，通常使用的发射正电子的放射性核素。该合成路线具有高度立体选择性的手性酯烯酸酯-亚胺环缩合，所得β-内酰胺的区域选择性加氢锡化以及新型乙烯基锡烷基紫杉烷中间体与碘甲烷的Stille偶联。已经建立了条件，可以在适合11 C-标记的时间范围内快速甲基化和HPLC纯化目标化合物，以用于PET研究。
• Synthesis and biological activity of novel 3′-trifluoromethyl taxoids
  作者：Iwao Ojima、John C. Slater、Paula Pera、Jean M. Veith、Ahmed Abouabdellah、Jean-Pierre Bégué、Ralph J. Bernacki

  DOI：10.1016/s0960-894x(96)00595-1

  日期：1997.1

  Second generation taxoids possessing a trifluoromethyl moiety in place of the 3'-phenyl group are synthesized by means of the beta-Lactam Synthon Method. The in vitro cytotoxicities of these new taxoids are evaluated against several different human cancer cell lines and found to exhibit greatly enhanced activities as compared to those of paclitaxel and docetaxel. The activity enhancement is most remarkable against a drug-resistant breast cancer cell line, MCF7-R, expressing MDR phenotype. (C) 1997, Elsevier Science Ltd.
• Biocatalysis of precursors to new-generation SB-T-taxanes effective against paclitaxel-resistant cancer cells
  作者：Aimen Al-Hilfi、Kevin D. Walker

  DOI：10.1016/j.abb.2022.109165

  日期：2022.4