7-triethylsilyl-10-dimethylcarbamoyl-10-deacetylbaccatin III | 160084-73-1

• 英文名称: 7-triethylsilyl-10-dimethylcarbamoyl-10-deacetylbaccatin III
• 英文别名: 10-N,N-dimethylcarbamoyl-7-triethylsilylbaccatin III；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(dimethylcarbamoyloxy)-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: 160084-73-1
• 化学式: C₃₈H₅₅NO₁₁Si
• 分子量: 729.94
• InChiKey: ZJNZGMQSXUSOCD-GXQWTKNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.82
• 重原子数：
  51
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  158
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  7-triethylsilyl-10-dimethylcarbamoyl-10-deacetylbaccatin III 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以90%的产率得到[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(dimethylcarbamoyloxy)-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  Taxanes Compounds, Preparation Method Therefor, and Uses Thereof

  摘要：

  本发明提供了具有式（I）或式（II）结构的紫杉醇化合物，以及制备这些化合物的方法，以及含有这些化合物、药学上可接受的盐和溶剂的组合物的用途，作为口服抗肿瘤药物的活性成分。在式（I）中，R1为—COR6，—COOR6或—CONR7aR7b；R2为C1-C6烷基，C1-C6烯基，取代的碳氢化合物基团，杂环基团，芳香基团或取代的芳香基团；R3为—OR6，—OCOOR6，—OCOSR6或—OCONR7aR7b；R4为—OR6，—OCOOR6，—OCOSR6，—OCONR7aR7b或H；其中，R6为C1-C6烷基，C1-C6烯基，C1-C6炔基，取代的碳氢化合物基团，芳香基团或杂环基团；R7a和R7b分别为氢，碳氢化合物基团，取代的碳氢化合物基团或杂环基团。在式（II）中，R1为—COR6或—COOR6；R2为芳香基团；R3为—OR6；其中，R6为C1-C6烷基，C1-C6烯基，C1-C6炔基，取代的碳氢化合物基团，芳香基团或杂环基团。

  公开号：

  US20160297784A1
• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 在 咪唑 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 7-triethylsilyl-10-dimethylcarbamoyl-10-deacetylbaccatin III
  参考文献：
  名称：

  新型紫杉烷类口服药物的合成

  摘要：

  合成了一组在紫杉醇的C-7，C-10，C-3'和C-14位置进行了修饰的新型类紫杉醇，以通过降低它们与P-糖蛋白（P-gp）的亲和力来改善其生物学特性）并增加细胞通透性。在体外，大多数新的类紫杉醇在MCF-7人肿瘤细胞系中表现出与紫杉醇相似的有效细胞毒性活性。在单层Caco-2细胞的通透性测定中，与紫杉醇相比，大多数化合物在A到B方向上表现出增加的跨细胞转运。其中的化合物T - 13，T - 15和T - 26表现出最高的渗透性，并且其流出率比Ortataxel更好。使用Madin-Darby犬肾（MDCK）-多药耐药-1（MDR1）和MDCK-野生型（WT）评估化合物T - 13和T - 26与P-gp的相互作用。结果表明，T - 13和T - 26是P-gp的底物，具有P-gp介导的外排的抑制作用。因此很明显，紫杉醇在C-7，C-10和C-3'位置的同时修饰显着削弱了其与P-gp的相互作用，并干扰了P-gp介导的外排。

  DOI：

  10.1016/j.bmc.2013.11.037

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
• TAXANE COMPOUND, AND PREPARATION METHOD AND USE THEREOF
  申请人：JIANGSU TASLY DIYI PHARMACEUTICAL CO., LTD.

  公开号：US20160340365A1

  公开（公告）日：2016-11-24

  Provided are taxanes compounds having the structure of formula I, preparation method thereof, and uses of compositions having the compound, pharmaceutical salts and solvates thereof as active ingredients in the preparation of oral antitumor drugs. In the formula, R 1 is —COR 6 , —COOR 6 , and —CONR 7a R 7b ; R 2 is C1-C6 alkyl, C1-C6 alkenyl group, a substituted hydrocarbon group, a heterocyclic group, an aromatic group or a substituted aromatic group; R 3 is —OR 6 , —OCOOR 6 , —OCOSR 6 , and —OCONR 7a R 7b ; R 4 is —OR 6 , —OCOOR 6 , —OCOSR 6 , —OCONR 7a R 7b , H, and OH; R 6 is C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl group, a substituted hydrocarbon group, an aromatic group or a heterocyclic group; and R 7a and R 7b are respectively hydrogen, a hydrocarbon group, a substituted hydrocarbon group or a heterocyclic group.

  提供了具有公式I结构的納豆化合物，其制备方法，以及将该化合物、药物盐和溶剂化合物用作口服抗肿瘤药物的用途。在公式中，R1为—COR6，—COOR6和—CONR7aR7b；R2为C1-C6烷基，C1-C6烯基，一个取代的碳氢基团，一个杂环基团，一个芳香基团或一个取代的芳香基团；R3为—OR6，—OCOOR6，—OCOSR6和—OCONR7aR7b；R4为—OR6，—OCOOR6，—OCOSR6，—OCONR7aR7b，H和OH；R6为C1-C6烷基，C1-C6烯基，C1-C6炔基，一个取代的碳氢基团，一个芳香基团或一个杂环基团；R7a和R7b分别为氢，一个碳氢基团，一个取代的碳氢基团或一个杂环基团。
• Structure–activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells
  作者：Iwao Ojima、Cecilia L Fumero-Oderda、Scott D Kuduk、Zhuping Ma、Fumiko Kirikae、Teruo Kirikae

  DOI：10.1016/s0968-0896(03)00181-0

  日期：2003.7

  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.
• Syntheses and Structure−Activity Relationships of the Second-Generation Antitumor Taxoids:  Exceptional Activity against Drug-Resistant Cancer Cells
  作者：Iwao Ojima、John C. Slater、Evelyne Michaud、Scott D. Kuduk、Pierre-Yves Bounaud、Patricia Vrignaud、Marie-Christine Bissery、Jean M. Veith、Paula Pera、Ralph J. Bernacki

  DOI：10.1021/jm9604080

  日期：1996.1.1

  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.