(E)-2',4',6'-trimethoxystyryl-4-methoxy-3-nitrobenzylsulfone

• 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: (E)-2',4',6'-trimethoxystyryl-4-methoxy-3-nitrobenzylsulfone
• 英文别名: 2-((E)-2-(4-methoxy-3-nitrobenzylsulfonyl)vinyl)-1,3,5-trimethoxybenzene；(E)-2,4,6-trimethoxystyryl-3'-nitro-4'-methoxybenzylsulfone；(E)-2,4,6-Trimethoxystyryl 4-Methoxy-3-Nitrobenzyl sulfone；1,3,5-trimethoxy-2-[(E)-2-[(4-methoxy-3-nitrophenyl)methylsulfonyl]ethenyl]benzene
• 化学式: C₁₉H₂₁NO₈S
• 分子量: 423.444
• InChiKey: XGRXGRFTLPXXAZ-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  125
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (E)-2',4',6'-trimethoxystyryl-4-methoxy-3-nitrobenzylsulfone 在 水 、 sodium acetate 、 sodium carbonate 作用下， 生成 瑞格色替
  参考文献：
  名称：

  Synthesis and biological evaluation of benzyl styrylsulfonyl derivatives as potent anticancer mitotic inhibitors

  摘要：

  We herein report the synthesis, biological activity and structure activity relationship of derivatives of benzylstyrylsulfone, benzylstyrylsulfine and benzylsulfonyl-N-phenylacetamide. A lead compound 7 represents a new class of mitotic inhibitors that demonstrates potent anti-proliferative activity and selectively induces cancer cell apoptosis while sparing non-transformed lung fibroblast. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.041
• 作为产物：
  描述：

  3-硝基-4-甲氧基苯甲醛 在 sodium tetrahydroborate 、 双氧水 、 三溴化磷 、 溶剂黄146 、 苄胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 28.5h， 生成 (E)-2',4',6'-trimethoxystyryl-4-methoxy-3-nitrobenzylsulfone
  参考文献：
  名称：

  Discovery of a Clinical Stage Multi-Kinase Inhibitor Sodium (E)-2-{2-Methoxy-5-[(2′,4′,6′-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na): Synthesis, Structure–Activity Relationship, and Biological Activity

  摘要：

  Cyclin D proteins are elevated in many cancer cells, and targeted deletion of cyclin D1 gene in the mammary tissues protects mice from breast cancer, Accordingly, there is an increasing awareness of this novel nonenzymatic target for cancer therapeutics. We have developed novel, nonalkylating styrylbenzylsulfones that induce cell death in wide variety of cancer cells without affecting the proliferation and survival of normal cells. The development of derivatized styrylbenzylsulfones followed logically from a tumor cell cytotoxicity screen performed in our laboratory that did not have an a priori target profile. Modifications of some of the precursor molecules led to lead optimization with regard to tumor cell cytotoxicity. In this report we describe the synthesis and structure-activity relationships of novel, nonalkylating (E)-styrylbenzylsulfones and the development of the novel anticancer agent sodium (E)-2-{2-methoxy-5-[(2',4',6'-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na), which is in phase III trials for myelodysplastic syndromes (MDS) associated with aberrant expression of cyclin D proteins.

  DOI：

  10.1021/jm200570p

文献信息

• [EN] 2,4,6-TRIALKOXYSTRYL ARYL SULFONES, SULFONAMIDES AND CARBOXAMIDES, AND METHODS OF PREPARATION AND USE<br/>[FR] 2,4,6-TRIALCOXYSTYRYLARYLSULFONES, SULFONAMIDES ET CARBOXAMIDES, ET PROCÉDÉS DE PRÉPARATION ET D'UTILISATION
  申请人：TEMPLE UNIV - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

  公开号：WO2017023912A1

  公开（公告）日：2017-02-09

  Compounds according to Formula (I) are provided and salts thereof, wherein R1, R2, R3, R4, R5, R6, R13, A, X and Y are as defined herein. Methods for preparing compounds of Formula (I) are also provided, as well as methods of treating cellular proliferative disorders, such as cancer, using compounds of Formula (I).

  根据公式（I）提供化合物及其盐，其中R1、R2、R3、R4、R5、R6、R13、A、X和Y的定义如本文所述。还提供了制备公式（I）化合物的方法，以及利用公式（I）化合物治疗细胞增殖性疾病，如癌症的方法。
• Hydrothiolation of benzyl mercaptan to arylacetylene: application to the synthesis of (E) and (Z)-isomers of ON 01910·Na (Rigosertib®), a phase III clinical stage anti-cancer agent
  作者：Venkat R. Pallela、Muralidhar R. Mallireddigari、Stephen C. Cosenza、Balaiah Akula、D. R. C. Venkata Subbaiah、E. Premkumar Reddy、M. V. Ramana Reddy

  DOI：10.1039/c3ob27220f

  日期：——

  A stereoselective and efficient method for free radical addition of benzyl thiol to aryl acetylene in the presence of Et3B-hexane has been developed for the synthesis of (Z) and (E)-styryl benzyl sulfides where base catalyzed hydrothiolations have failed. The scope of this reaction was successfully extended for the synthesis of (E)-ON 01910·Na, a phase III clinical stage anti-cancer agent and its inactive

  一种立体选择性且高效的自由基加成方法苄硫醇在 Et 3 B-己烷存在下将芳基乙炔转化为芳基乙炔已被开发用于合成 ( Z ) 和 ( E )-苯乙烯基苄基硫醚，其中碱催化的氢硫醇化已失败。该反应范围被成功扩展，用于合成III期临床抗癌药物( E )-ON 01910·Na及其无活性几何异构体( Z )-ON 01910·Na。有趣的是，与Z异构体相比，所有合成的E异构体都对癌细胞表现出更好的细胞毒性。
• COMPOSITION AND METHODS FOR THE TREATMENT OF MYELODYSPLASTIC SYNDROME AND ACUTE MYELOID LEUKEMIA
  申请人：Reddy E. Premkumar

  公开号：US20100305059A1

  公开（公告）日：2010-12-02

  Methods and compositions are provided for treating myelodysplastic syndrome and acute myeloid leukemia, wherein the composition comprises at least one compound according to Formula I: wherein R 1 is selected from the group consisting of —NH 2 , —NH—CH 2 —CO 2 H, —NH—CH(CH 3 )—CO 2 H, and —NH—C(CH 3 ) 2 —CO 2 H, or a pharmaceutically acceptable salt of such a compound; and a DNA methyltransferase inhibitor, or a pharmaceutically acceptable salt thereof.

  提供了用于治疗骨髓增生异常综合征和急性髓系白血病的方法和组合物，其中该组合物包括至少一种符合以下式I的化合物：其中R1选自—NH2、—NH—CH2—CO2H、—NH—CH(CH3)—CO2H和—NH—C(CH3)2—CO2H的群组，或者该化合物的药用可接受盐；以及DNA 甲基转移酶抑制剂，或其药用可接受盐。
• [EN] AMINO-SUBSTITUTED (E)-2,6-DIALKOXYSTYRYL 4-SUBSTITUTED BENZYLSULFONES FOR TREATING PROLIFERATIVE DISORDERS<br/>[FR] (E)- 2,6-DIALCOXYSTYRYLE A SUBSTITUTION AMINO-BENZYLSULFONES SUBSTITUEES EN POSITION 4 DESTINEES AU TRAITEMENT DE TROUBLES PROLIFERATIFS
  申请人：UNIV TEMPLE

  公开号：WO2003072062A2

  公开（公告）日：2003-09-04

  Compounds useful as antiproliferative agents, including, for example, anticancer agents, are provided according to formula (I); wherein: X, X1, X2, Ra, R1, R2, R3, R4, R5, R6, R7, g, M, y, a, b, d, e, V, W, Z and Q are as defined herein.

  提供了作为抗增殖剂有用的化合物，包括例如抗癌剂，其按照公式（I）提供；其中：X，X1，X2，Ra，R1，R2，R3，R4，R5，R6，R7，g，M，y，a，b，d，e，V，W，Z和Q如此定义。
• Amino-substituted (e)-2,6-dialkoxystyryl 4-substituted-benzylsulfones for treating proliferative disorders
  申请人：Reddy Premkumar E.

  公开号：US20050130942A1

  公开（公告）日：2005-06-16

  Compounds useful as antiproliferative agents, including, for example, anticancer agents, are provided according to formula (I); wherein: X, X 1 , X 2 , R a , R 1 , R 2 ,R 3 , R 4 , R 5 , R 6 , R 7 , g, M, y, a, b, d, e, V, W, Z and Q are as defined herein.

  提供了作为抗增殖剂有用的化合物，包括例如抗癌剂，其符合公式（I）; 其中：X、X1、X2、Ra、R1、R2、R3、R4、R5、R6、R7、g、M、y、a、b、d、e、V、W、Z和Q如此处所定义。