[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,9,15-trihydroxy-10,14,17,17-tetramethyl-12-[(E)-3-naphthalen-2-ylprop-2-enoyl]oxy-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate | 872852-70-5

• 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: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,9,15-trihydroxy-10,14,17,17-tetramethyl-12-[(E)-3-naphthalen-2-ylprop-2-enoyl]oxy-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 872852-70-5
• 化学式: C₄₂H₄₄O₁₁
• 分子量: 724.805
• InChiKey: HHIGRWHLRMRUDY-LUZZEONASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  53
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  166
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (E)-3-(萘-2-基)丙烯酸 、 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,9,15-trihydroxy-10,14,17,17-tetramethyl-12-[(E)-3-naphthalen-2-ylprop-2-enoyl]oxy-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,15-dihydroxy-10,14,17,17-tetramethyl-9,12-bis[[(E)-3-naphthalen-2-ylprop-2-enoyl]oxy]-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  Design, Synthesis and Structure−Activity Relationships of Novel Taxane-Based Multidrug Resistance Reversal Agents

  摘要：

  A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure-activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonyleinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.

  DOI：

  10.1021/jm049483y
• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 在 吡啶 、 氟化氢吡啶 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,9,15-trihydroxy-10,14,17,17-tetramethyl-12-[(E)-3-naphthalen-2-ylprop-2-enoyl]oxy-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  New taxanes as highly efficient reversal agents for multi-drug resistance in cancer cells

  摘要：

  New non-cytotoxic taxanes synthesized from 10-deacetylbaccatin III and special hydrophobic acylating agents show remarkable MDR reversal activity (less than or equal to 99.8%) against drug-resistant human breast cancer cells when co-administered with paclitaxel or doxorubicin. This activity is ascribed to the highly efficient blocking of P-glycoprotein efflux by these new taxanes. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(97)10218-9

文献信息

• Targeting FtsZ for Antituberculosis Drug Discovery:  Noncytotoxic Taxanes as Novel Antituberculosis Agents
  作者：Qing Huang、Fumiko Kirikae、Teruo Kirikae、Antonella Pepe、Amol Amin、Laurel Respicio、Richard A. Slayden、Peter J. Tonge、Iwao Ojima

  DOI：10.1021/jm050920y

  日期：2006.1.1

  Screening of 120 taxanes identified a number of compounds that exhibited significant antituberculosis activity. Rational optimization of selected compounds led to the discovery that the C-seco-taxane-multidrug-resistance (MDR) reversal agents (C-seco-TRAs) are non-cytotoxic at the upper limit of solubility and detection (> 80 mu M), while maintaining MIC99 values of 1.25-2.5 mu M against drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis (MTB). Treatment of MTB cells with TRA 3aa and 10a at the MIC caused filamentation and prolongation of the cells, a phenotypic response to FtsZ inactivation.
• Design, Synthesis and Structure−Activity Relationships of Novel Taxane-Based Multidrug Resistance Reversal Agents
  作者：Iwao Ojima、Christopher P. Borella、Xinyuan Wu、Pierre-Yves Bounaud、Cecilia Fumero Oderda、Matthew Sturm、Michael L. Miller、Subrata Chakravarty、Jin Chen、Qing Huang、Paula Pera、Tracy A. Brooks、Maria R. Baer、Ralph J. Bernacki

  DOI：10.1021/jm049483y

  日期：2005.3.1

  A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure-activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonyleinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.
• New taxanes as highly efficient reversal agents for multi-drug resistance in cancer cells
  作者：Iwao Ojima、Pierre-Yves Bounaud、Craig Takeuchi、Paula Pera、Ralph J. Bernacki

  DOI：10.1016/s0960-894x(97)10218-9

  日期：1998.1

  New non-cytotoxic taxanes synthesized from 10-deacetylbaccatin III and special hydrophobic acylating agents show remarkable MDR reversal activity (less than or equal to 99.8%) against drug-resistant human breast cancer cells when co-administered with paclitaxel or doxorubicin. This activity is ascribed to the highly efficient blocking of P-glycoprotein efflux by these new taxanes. (C) 1998 Elsevier Science Ltd. All rights reserved.