1,2,3-trimethoxy-5-((E)-4-methoxy-2-nitrostyryl)benzene

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1,2,3-trimethoxy-5-((E)-4-methoxy-2-nitrostyryl)benzene
• 英文别名: 1,2,3-trimethoxy-5-[(E)-2-(4-methoxy-2-nitrophenyl)ethenyl]benzene
• 化学式: C₁₈H₁₉NO₆
• 分子量: 345.352
• InChiKey: YNTLZOPNNKBFCN-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-甲氧基-2-硝基溴苄 在 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 1,2,3-trimethoxy-5-((E)-4-methoxy-2-nitrostyryl)benzene
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of combretastatin nitrogen-containing derivatives as inhibitors of tubulin assembly and vascular disrupting agents

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2005.12.033

文献信息

• Design, synthesis, and biological evaluation of water-soluble amino acid prodrug conjugates derived from combretastatin, dihydronaphthalene, and benzosuberene-based parent vascular disrupting agents
  作者：Laxman Devkota、Chen-Ming Lin、Tracy E. Strecker、Yifan Wang、Justin K. Tidmore、Zhi Chen、Rajsekhar Guddneppanavar、Christopher J. Jelinek、Ramona Lopez、Li Liu、Ernest Hamel、Ralph P. Mason、David J. Chaplin、Mary Lynn Trawick、Kevin G. Pinney

  DOI：10.1016/j.bmc.2016.01.007

  日期：2016.3

  with improved water solubility and potentially greater bioavailability, various amino acid prodrug conjugates (AAPCs) of potent amino combretastatin, amino dihydronaphthalene, and amino benzosuberene analogs were synthesized along with their corresponding water-soluble hydrochloride salts. These compounds were evaluated for their ability to inhibit tubulin polymerization and for their cytotoxicity against

  靶向肿瘤脉管系统代表了在癌症治疗中的一种有趣的治疗策略。为了发现具有改善的水溶性和潜在更高的生物利用度的新的血管破坏剂，合成了有效的氨基康他汀，氨基二氢萘和氨基苯甲sub烯类似物的各种氨基酸前药共轭物（AAPC）及其相应的水溶性盐酸盐。对这些化合物抑制微管蛋白聚合的能力以及对选定的人类癌细胞系的细胞毒性进行了评估。基于氨基的亲本抗癌药7、8、32（也称为KGP05）和33（也称为KGP156）在所有评估的细胞系中均显示出强大的细胞毒性（GI50 = 0.11-40nM），它们是微管蛋白聚合的强抑制剂（IC50 =0.62-1.5μM）。研究了各种前药缀合物及其相应的盐是否被亮氨酸氨基肽酶（LAP）切割。甘氨酸水溶性AAPC中有四个（16、18、44和45）显示LAP定量裂解，导致释放出高细胞毒性母体药物，而其他前药则观察到部分裂解（<10-90％）（ 15、17、24、38和39）。19枚
• 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.