(E)-methyl 2'',2''-difluoro-2(2-methoxy-5-((2',4',6'-trimethoxystyrylsulfonyl)methyl)phenylamino)acetate | 1330633-90-3

• 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)-methyl 2'',2''-difluoro-2(2-methoxy-5-((2',4',6'-trimethoxystyrylsulfonyl)methyl)phenylamino)acetate
• 英文别名: methyl 2,2-difluoro-2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetate
• CAS: 1330633-90-3
• 化学式: C₂₂H₂₅F₂NO₈S
• 分子量: 501.505
• InChiKey: JNDKKGXIAUYVAO-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (E)-methyl 2'',2''-difluoro-2(2-methoxy-5-((2',4',6'-trimethoxystyrylsulfonyl)methyl)phenylamino)acetate 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以59%的产率得到(E)-2'',2''-difluoro-2-(2-methoxy-5-((2',4',6'-trimethoxystyrylsulfonyl)methyl)phenylamino)acetic 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
• 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 、 sodium acetate 、 间氯过氧苯甲酸 、 三苯基膦 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)-methyl 2'',2''-difluoro-2(2-methoxy-5-((2',4',6'-trimethoxystyrylsulfonyl)methyl)phenylamino)acetate
  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

• Discovery of a Clinical Stage Multi-Kinase Inhibitor Sodium (<i>E</i>)-2-{2-Methoxy-5-[(2′,4′,6′-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na): Synthesis, Structure–Activity Relationship, and Biological Activity
  作者：M. V. Ramana Reddy、Padmavathi Venkatapuram、Muralidhar R. Mallireddigari、Venkat R. Pallela、Stephen C. Cosenza、Kimberly A. Robell、Balaiah Akula、Benjamin S. Hoffman、E. Premkumar Reddy

  DOI：10.1021/jm200570p

  日期：2011.9.22

  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.