(E)-2-(5-(2,4,6-trimethoxystyrylsulfonylmethyl)-2-methoxyphenylamino)-propanoic acid | 592542-82-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (E)-2-(5-(2,4,6-trimethoxystyrylsulfonylmethyl)-2-methoxyphenylamino)-propanoic acid
• 英文别名: ON012380；(E)-2-(2-methoxy-5-((2',4',6'-trimethoxystyrylsulfonyl)-methyl)phenylamino)propanoic acid；racemic-(E)-2,4,6-trimethoxystyryl-3-(1-carboxyethyl)amino-4-methoxy-benzylsulfone；(E)-2,4,6-trimethoxystyryl-3-(1-carboxyethyl)amino-4-methoxybenzylsulfone；racemic-2-(5-(((E)-2,4,6-trimethoxystyrylsulfonyl)-methyl)-2-methoxyphenylamino)-propanoic acid；(E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)propanoic acid；2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]propanoic acid
• CAS: 592542-82-0
• 化学式: C₂₂H₂₇NO₈S
• 分子量: 465.524
• InChiKey: KLFKGEAXNPYTKB-CMDGGOBGSA-N

物化性质

• 熔点：
  116-118 °C(Solv: acetone (67-64-1))
• 沸点：
  752.7±60.0 °C(Predicted)
• 密度：
  1.309±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2,4,6-三甲氧基苯甲醛 在 正丁基锂 、 sodium dithionite 、 三乙基硼 、 水 、 sodium acetate 、 间氯过氧苯甲酸 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 丙酮 、 苯 为溶剂， 反应 54.92h， 生成 (E)-2-(5-(2,4,6-trimethoxystyrylsulfonylmethyl)-2-methoxyphenylamino)-propanoic acid
  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

• 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。
• Unsaturated Sulfides, Sulfones, Sulfoxides and Sulfonamides Synthesis
  申请人：Reddy M.V. Ramana

  公开号：US20090124828A1

  公开（公告）日：2009-05-14

  α,β-Unsaturated sulfides, sulfones, sulfoxides and sulfonamides according to Formula I: wherein Ar 1 , Ar 2 , X, n, * and R are as defined herein, are prepared by dehydration of β-hydroxy sulfides, sulfones, sulfoxides or sulfonamides.

  根据公式I，制备α，β-不饱和硫化物，磺酰酸，亚磺酸和磺酰胺，其中Ar1，Ar2，X，n，*和R的定义如下，通过β-羟基硫化物，磺酰酸，亚磺酸或磺酰胺的脱水反应制备。
• Treatment of proliferative disorders with amino-substituted (E)-2,6- dialkoxystyryl 4-substituted benzylsulfones
  申请人：Reddy E. Premkumar

  公开号：US20090281066A1

  公开（公告）日：2009-11-12

  Methods of treating cancer using compounds according to Formula (I) are disclosed herein, 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.

  本文披露了使用公式（I）中的化合物治疗癌症的方法，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的定义如下。