3-((tert-butyldimethylsilyl)oxy)-4-methoxy-2-nitrobenzaldehyde | 886442-63-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-((tert-butyldimethylsilyl)oxy)-4-methoxy-2-nitrobenzaldehyde
• 英文别名: 3-(tert-butyldimethylsilyloxy)-4-methoxy-2-nitrobenzaldehyde；3-tert-butyldimethylsilyloxy-4-methoxy-2-nitrobenzaldehyde
• CAS: 886442-63-3
• 化学式: C₁₄H₂₁NO₅Si
• 分子量: 311.41
• InChiKey: QWGWYNHGZPBWCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  78.67
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-((tert-butyldimethylsilyl)oxy)-4-methoxy-2-nitrobenzaldehyde 在 四丁基氟化铵 、 甲酸铵 、 sodium hydride 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 氘代甲醇-d 为溶剂， 反应 13.0h， 生成 (E)-3-(4-chlorophenyl)-N-(2-hydroxy-3-methoxy-6-((Z)-3,4,5-trimethoxystyryl)phenyl)acrylamide
  参考文献：
  名称：

  芳基肉桂酰胺连接的康维他汀-A4杂合体作为微管蛋白聚合抑制剂和凋亡诱导剂的合成及生物学评价。

  摘要：

  通过结合芳基肉桂酰胺和康维他汀药效基团，在杂交方法的基础上设计了一系列新分子。合成并评估它们的细胞毒性活性，对微管蛋白聚合的抑制作用和凋亡诱导能力。大多数缀合物对某些代表性的人类癌细胞系均表现出显着的细胞毒性活性，其中两个缀合物6i和6p表现出强的细胞毒性，其对人乳腺癌细胞系（MCF-7）的GI50值分别为56nM和31nM。SAR研究表明，肉桂酰胺部分苯环上的3,4-取代有利于增强细胞毒性。此外，除了微管蛋白聚合抑制（IC50为1.97μM和1.之外），这些结合物（6i和6p）还诱导了G2 / M细胞周期阻滞。分别为05μM）。此外，线粒体膜电位，膜联蛋白V-FITC和caspase-9活化试验表明，这些结合物可通过凋亡诱导细胞死亡。对接研究表明，这些结合物在微管蛋白的秋水仙碱结合位点相互作用并结合。

  DOI：

  10.1016/j.bmcl.2016.03.049
• 作为产物：
  描述：

  异香兰素 在 咪唑 、 nitronium tetrafluoborate 作用下， 以 硝基甲烷 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 3-((tert-butyldimethylsilyl)oxy)-4-methoxy-2-nitrobenzaldehyde
  参考文献：
  名称：

  芳基肉桂酰胺连接的康维他汀-A4杂合体作为微管蛋白聚合抑制剂和凋亡诱导剂的合成及生物学评价。

  摘要：

  通过结合芳基肉桂酰胺和康维他汀药效基团，在杂交方法的基础上设计了一系列新分子。合成并评估它们的细胞毒性活性，对微管蛋白聚合的抑制作用和凋亡诱导能力。大多数缀合物对某些代表性的人类癌细胞系均表现出显着的细胞毒性活性，其中两个缀合物6i和6p表现出强的细胞毒性，其对人乳腺癌细胞系（MCF-7）的GI50值分别为56nM和31nM。SAR研究表明，肉桂酰胺部分苯环上的3,4-取代有利于增强细胞毒性。此外，除了微管蛋白聚合抑制（IC50为1.97μM和1.之外），这些结合物（6i和6p）还诱导了G2 / M细胞周期阻滞。分别为05μM）。此外，线粒体膜电位，膜联蛋白V-FITC和caspase-9活化试验表明，这些结合物可通过凋亡诱导细胞死亡。对接研究表明，这些结合物在微管蛋白的秋水仙碱结合位点相互作用并结合。

  DOI：

  10.1016/j.bmcl.2016.03.049

文献信息

• Design and Synthesis of Aminostilbene-Arylpropenones as Tubulin Polymerization Inhibitors
  作者：Ahmed Kamal、G. Bharath Kumar、Sowjanya Polepalli、Anver Basha Shaik、Vangala Santhosh Reddy、M. Kashi Reddy、Ch. Ratna Reddy、Rasala Mahesh、Jeevak Sopanrao Kapure、Nishant Jain

  DOI：10.1002/cmdc.201402256

  日期：2014.11

  A series of aminostilbene—arylpropenones were designed and synthesized by Michael addition and were investigated for their cytotoxic activity against various human cancer cell lines. Some of the investigated compounds exhibited significant antiproliferative activity against a panel of 60 human cancer cell lines of the US National Cancer Institute, with 50 % growth inhibition (GI50) values in the range

  通过迈克尔加成法设计和合成了一系列氨基二苯乙烯-芳基丙烯酮，并研究了它们对多种人类癌细胞系的细胞毒活性。某些所研究的化合物均显示出显著抗增殖活性对抗的美国国家癌症研究所的60个人癌症细胞系中，用50％的生长抑制（GI 50）值的范围在从<0.01至19.9μ中号。一项的化合物的抗增殖表现出功效的广谱上大部分的细胞系，用GI 50 <0.01μ的值中号。所有合成的化合物对A549（非小细胞肺癌），HeLa（宫颈癌），MCF-7（乳腺癌）和HCT116（结肠癌）均具有50％抑制浓度（IC 50）值的细胞毒性。从0.011到8.56μ中号。细胞周期测定表明，这些化合物阻止了细胞周期的G2 / M期。两种化合物对微管蛋白与IC表现出强烈的抑制作用组件50倍的0.71的值和0.79μ中号。此外，对细胞周期蛋白B1的斑点印迹分析表明，某些同类物强烈诱导细胞周期蛋白B1蛋白水平。分子对接研究表明，这些化合物占据了微管蛋白的秋水仙碱结合位点。
• Design, Synthesis, and in vitro and in vivo Evaluations of (<i>Z</i>)-3,4,5-Trimethoxystyrylbenzenesulfonamides/sulfonates as Highly Potent Tubulin Polymerization Inhibitors
  作者：Rasala Mahesh、Vadithe Lakshma Nayak、Korrapati Suresh Babu、Syed Riyaz、Thokhir Basha Shaik、Gajjela Bharth Kumar、Prema Latha Mallipeddi、Challa Ratna Reddy、Kunta Chandra Shekar、Jedy Jose、Narayana Nagesh、Ahmed Kamal

  DOI：10.1002/cmdc.201600643

  日期：2017.5.9

  5-trimethoxystyryl)phenyl]-4-methoxybenzenesulfonamide (9 a) were found to be potent. Similar results were obtained against three human cancer cell lines with IC50 values ranging between 0.04 and 3.0 μm. Studies aimed at elucidating the mechanism of action of these new analogues revealed that they inhibited the in vitro polymerization of tubulin and disorganized the assembly of microtubules in HeLa and MCF-7cancer

  可以通过采用从已知生物活性化合物对特有支架进行支架跳跃的策略，在药物开发中开发出新的疗法。该策略已在药物发现过程中广泛采用。基于结构的对接研究阐明了基本的基本概念，并揭示了磺酰胺基团的相互作用和疏水性相互作用至关重要。在此策略的基础上，合成了60多种合成类似物，并评估了其对60种人类癌细胞系NCI检测的细胞毒性。这些化合物大多数显示出有希望的细胞毒性，GI50值在18至50 nm之间。在这些化合物中，（Z）-N- [2,3-二甲氧基-5-（3,4,5-三甲氧基苯乙烯基）苯基] -4-甲氧基苯磺酰胺（7a）和（Z）-N- [2-羟基- 3-甲氧基-6-（3,4，发现5-三甲氧基苯乙烯基）苯基] -4-甲氧基苯磺酰胺（9a）是有效的。针对三种人类癌细胞系，IC50值介于0.04至3.0μm之间，也获得了相似的结果。旨在阐明这些新类似物作用机理的研究表明，它们抑制了微管蛋白的体外聚合，并破坏了H
• Design, Synthesis, and Biological Evaluation of Combretabenzodiazepines: A Novel Class of Anti-Tubulin Agents
  作者：Ubaldina Galli、Cristina Travelli、Silvio Aprile、Elena Arrigoni、Simone Torretta、Giorgio Grosa、Alberto Massarotti、Giovanni Sorba、Pier Luigi Canonico、Armando A. Genazzani、Gian Cesare Tron

  DOI：10.1021/jm5016389

  日期：2015.2.12

  In the present manuscript, starting from the 1,4-benzodiazepin-2-one nucleus, a privileged structure in medicinal chemistry, we have synthesized a novel class of cis-locked combretastatins named combreatabenzodiazepines. They show similar cytotoxic and antitubulin activity compared to combretastatin A-4 in neuroblastoma cells, showing a better pharmacokinetic profile. This class of compounds has therefore

  在本手稿中，从1,4-苯并二氮杂-2-酮核（一种药物化学中的特权结构）开始，我们合成了一类新型的顺式锁康维他汀类药物，称为康柏他唑二氮杂。与康普他汀A-4在神经母细胞瘤细胞中相比，它们显示出相似的细胞毒性和抗微管蛋白活性，表现出更好的药代动力学特征。因此，这类化合物具有作为抗微管蛋白剂进一步开发的潜力。
• Design, synthesis, and biological evaluation of combretastatin nitrogen-containing derivatives as inhibitors of tubulin assembly and vascular disrupting agents
  作者：Keith A. Monk、Rogelio Siles、Mallinath B. Hadimani、Benon E. Mugabe、J. Freeland Ackley、Scott W. Studerus、Klaus Edvardsen、Mary Lynn Trawick、Charles M. Garner、Monte R. Rhodes、George R. Pettit、Kevin G. Pinney

  DOI：10.1016/j.bmc.2005.12.033

  日期：2006.5

  A series of analogs with nitro or serinamide substituents at the C-2'-, C-5'-, or C-C-position of the combretastatin A-4 (CA4) B-ring was synthesized and evaluated for cytotoxic effects against heart endothelioma cells, blood flow reduction to tumors in SCID mice, and as inhibitors of tubulin polymerization. The synthesis of these analogs typically featured a Wittig reaction between a suitably functionalized arylaldehyde and an arylphosphonium salt followed by separation of the resultant F and Z-isomers. several of these nitrogen-modified CA4 derivatives (both amino and nitro) demonstrate significant inhibition of tubulin assembly as well as cytotoxicity and in vivo blood flow reduction. 2'-Aminostilbenoid 7 and 2'-amino-3'-hydroxystilbenoid 29 proved to be the most active in this series. Both compounds, 7 and 29, have the potential for further pro-drug modification and development as vascular disrupting agents for treatment of solid tumor cancers and certain ophthalmological diseases. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of 1,2,3-triazole linked aminocombretastatin conjugates as mitochondrial mediated apoptosis inducers
  作者：Ahmed Kamal、Bajee Shaik、V. Lakshma Nayak、Burri Nagaraju、Jeevak Sopanrao Kapure、M. Shaheer Malik、Thokhir Basha Shaik、B. Prasad

  DOI：10.1016/j.bmc.2014.08.008

  日期：2014.10

  A series of 1,2,3-triazole linked aminocombretastatin conjugates were synthesized and evaluated for cytotoxicity, inhibition of tubulin polymerization and apoptosis inducing ability. Most of the conjugates exhibited significant anticancer activity against some representative human cancer cell lines and two of the conjugates 6d and 7c displayed potent cytotoxicity with IC50 values of 53 nM and 44 nM against A549 human lung cancer respectively, and were comparable to combretastatin A-4 (CA-4). SAR studies revealed that 1-benzyl substituted triazole moiety with an amide linkage at 3-position of B-ring of the combretastatin subunit are more active compared to 2-position. G2/M cell cycle arrest was induced by these conjugates 6d and 7c and the tubulin polymerization assay (IC50 of 1.16 μM and 0.95 μM for 6d and 7c, respectively) as well as immunofluorescence analysis showed that these conjugates effectively inhibit microtubule assembly at both molecular and cellular levels in A549 cells. Colchicine competitive binding assay suggested that these conjugates bind at the colchicine binding site of tubulin as also observed from the docking studies. Further, mitochondrial membrane potential, ROS generation, caspase-3 activation assay, Hoechst staining and DNA fragmentation analysis revealed that these conjugates induce cell death by apoptosis.