6-methoxy-3-nitrobenzylsulfonylacetic acid | 243142-39-4

• 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: 6-methoxy-3-nitrobenzylsulfonylacetic acid
• 英文别名: 2-[(2-Methoxy-5-nitrophenyl)methylsulfonyl]acetic acid
• CAS: 243142-39-4
• 化学式: C₁₀H₁₁NO₇S
• mdl: MFCD12446209
• 分子量: 289.266
• InChiKey: OAGVGSFXLRIMDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-methoxy-3-nitrobenzylsulfonylacetic acid 在 sodium dithionite 、 溶剂黄146 、 苄胺 作用下， 以 水 、 丙酮 为溶剂， 反应 1.0h， 生成 (E)-2',6'-dimethoxystyryl-6-methoxy-3-aminobenzylsulfone
  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-甲氧基-5-硝基苯基)甲醇 在 双氧水 、 三溴化磷 、 溶剂黄146 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 27.5h， 生成 6-methoxy-3-nitrobenzylsulfonylacetic 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

• Substituted styryl benzylsulfones for treating proliferative disorders
  申请人：——

  公开号：US20020115643A1

  公开（公告）日：2002-08-22

  Styryl benzylsulfones of formula I are useful as antiproliferative agents, including, for example, anticancer agents: 1 wherein (a) (i) at least three of R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, cyano, carboxyl, hydroxyl, phosphonato, amino, sulfamyl, acetoxy, dimethylamino(C2-C6 alkoxy) and trifluoromethyl, and the balance of said R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, cyano, carboxyl, hydroxyl, phosphonato, amino, sulfamyl, acetoxy, dimethylamino(C2-C6 alkoxy) and trifluoromethyl; and (ii) R 6 , R 7 , R 8 , R 9 and R 10 are independently selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, cyano, carboxyl, hydroxyl, phosphonato, amino, sulfamyl, acetoxy, dimethylamino(C2-C6 alkoxy) and trifluoromethyl; or (b) (i) at least three of R 6 , R 7 , R 8 , R 9 and R 10 are independently selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, cyano, carboxyl, hydroxyl, phosphonato, amino, sulfamyl, acetoxy, dimethylamino(C2-C6 alkoxy) and trifluoromethyl, and the balance of said R 6 , R 7 , R 8 , R 9 and R 10 are independently selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, cyano, carboxyl, hydroxyl, phosphonato, amino, sulfamyl, acetoxy, dimethylamino(C2-C6 alkoxy) and trifluoromethyl; and (ii) R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, cyano, carboxyl, hydroxyl, phosphonato, amino, sulfamyl, acetoxy, dimethylamino(C2-C6 alkoxy) and trifluoromethyl; or a pharmaceutically acceptable salt thereof.

  式I的苯基砜基苯乙烯是有用的抗增殖剂，包括例如抗癌剂：其中 (a) (i) R1、R2、R3、R4和R5中至少三个独立地选自卤素、C1-C6烷基、C1-C6烷氧基、硝基、氰基、羧基、羟基、膦酸基、氨基、磺胺基、乙酰氧基、二甲胺基(C2-C6烷氧基)和三氟甲基的群组，以及所述的R1、R2、R3、R4和R5的余下部分独立地选自氢、卤素、C1-C6烷基、C1-C6烷氧基、硝基、氰基、羧基、羟基、膦酸基、氨基、磺胺基、乙酰氧基、二甲胺基(C2-C6烷氧基)和三氟甲基的群组；和 (ii) R6、R7、R8、R9和R10独立地选自氢、卤素、C1-C6烷基、C1-C6烷氧基、硝基、氰基、羧基、羟基、膦酸基、氨基、磺胺基、乙酰氧基、二甲胺基(C2-C6烷氧基)和三氟甲基的群组；或 (b) (i) R6、R7、R8、R9和R10中至少三个独立地选自卤素、C1-C6烷基、C1-C6烷氧基、硝基、氰基、羧基、羟基、膦酸基、氨基、磺胺基、乙酰氧基、二甲胺基(C2-C6烷氧基)和三氟甲基的群组，以及所述的R6、R7、R8、R9和R10的余下部分独立地选自氢、卤素、C1-C6烷基、C1-C6烷氧基、硝基、氰基、羧基、羟基、膦酸基、氨基、磺胺基、乙酰氧基、二甲胺基(C2-C6烷氧基)和三氟甲基的群组；和 (ii) R1、R2、R3、R4和R5独立地选自氢、卤素、C1-C6烷基、C1-C6烷氧基、硝基、氰基、羧基、羟基、膦酸基、氨基、磺胺基、乙酰氧基、二甲胺基(C2-C6烷氧基)和三氟甲基的群组；或其药学上可接受的盐。
• Substituted benzylthioacetic acids and esters
  申请人：——

  公开号：US20030036536A1

  公开（公告）日：2003-02-20

  Styryl benzylsulfones of formula I are useful as antiproliferative agents, including, for example, anticancer agents: 1 wherein R 1 through R 10 are defined herein; or a pharmaceutically acceptable salt thereof.

  式I中的苯基磺酰苯基烷基化合物是一种有用的抗增殖剂，包括例如抗癌剂：1其中R1至R10在此定义；或其药学上可接受的盐。
• Substituted (e)-styryl benzylsulfones for treating proliferative disorders
  申请人：Reddy Premkumar E.

  公开号：US20050101528A1

  公开（公告）日：2005-05-12

  (E)-Styryl benzylsulfones useful as antiproliferative agents, including, for example, anticancer agents, are provided according to formula I: wherein: R 1 is selected from the group consisting of halogen, C1-C6 alkoxy, nitro, phosphonato, amino, sulfamyl, carboxy, acetoxy and dimethylamino (C2-C6 alkoxy); and R 2 and R 3 are independently selected from the group consisting of halogen, C1-C6 alkoxy, C1-C6 alkyl, nitro, cyano, hydroxyl, phosphonato, amino, sulfamyl, carboxy, acetoxy, and dimethylamino (C2-C6 alkoxy); provided: R 1 may not be halogen when R 2 and R 3 are both halogen; R 2 may not be 2-halogen when R 3 is 4-halogen; or a pharmaceutically acceptable salt thereof; or formula II: wherein: R 4 is selected from the group consisting of C1-C6 alkoxy, phosphonato, amino, sulfamyl, carboxy, acetoxy and dimethylamino (C2-C6 alkoxy); R 6 is selected from the group consisting of nitro, hydrogen, phosphonato, amino, sulfamyl, carboxy, acetoxy and dimethylamino (C2-C6 alkoxy); and R 7 is selected from the group consisting of halogen, C1-C6 alkoxy, C1-C6 alkyl, nitro, cyano, hydroxy, phosphonato, amino, sulfamyl, carboxy, acetoxy, dimethylamino (C2-C6 alkoxy) and trifluoromethyl; provided R 5 and R 6 may not be hydrogen in the same compound; or a pharmaceutically acceptable salt thereof.

  (E)-苯乙烯基苄基砜可用作抗增殖剂，例如包括抗癌剂，其根据式 I 提供： 其中：R 1 选自由卤素、C1-C6 烷氧基、硝基、膦酰基、氨基、氨基磺酰基、羧基、乙酰氧基和二甲基氨基（C2-C6 烷氧基）组成的组；以及 R 2 和 R 3 独立选自由卤素、C1-C6 烷氧基、C1-C6 烷基、硝基、氰基、羟基、膦酰基、氨基、氨基磺酰基、羧基、乙酰氧基和二甲基氨基（C2-C6 烷氧基）组成的组；前提是R 1 不得为卤素，当 R 2 和 R 3 都是卤素时 2 当 R 3 为 4-卤素时，R 2 不得为 2-卤素；或其药学上可接受的盐；或式 II： 其中R 4 选自由 C1-C6 烷氧基、膦酸、氨基、氨基磺酰基、羧基、乙酰氧基和二甲基氨基（C2-C6 烷氧基）组成的组 6 选自由硝基、氢、膦酰基、氨基、氨基磺酰基、羧基、乙酰氧基和二甲基氨基 （C2-C6 烷氧基）组成的组；以及 R 7 选自由卤素、C1-C6 烷氧基、C1-C6 烷基、硝基、氰基、羟基、膦酰基、氨基、氨基磺酰基、羧基、乙酰氧基、二甲基氨基（C2-C6 烷氧基）和三氟甲基组成的组；前提是 R 5 和 R 6 或其药学上可接受的盐。
• [EN] SUBSTITUTED (E)-STYRYL BENZYLSULFONES FOR TREATING PROLIFERATIVE DISORDERS<br/>[FR] (E)-STYRYL BENZYLSULFONES SUBSTITUES DESTINES AU TRAITEMENT DE TROUBLES A EVOLUTION CHRONIQUE
  申请人：UNIV TEMPLE

  公开号：WO2002028828A1

  公开（公告）日：2002-04-11

  (E)-Styryl benzylsulfones useful as antiproliferative agents, including, for example, anticancer agents, are provided according to formula I: wherein: R1 is selected from the group consisting of halogen, C1-C6 alkoxy, nitro, phosphonato, amino, sulfamyl, carboxy, acetoxy and dimethylamino (C2-C6 alkoxy); and R2 and R3 are independently selected from the group consisting of halogen, C1-C6 alkoxy, C1-C6 alkyl, nitro, cyano, hydroxy, phosphonato, amino, sulfamyl, carboxy, acetoxy, and dimethylamino (C2-C6 alkoxy); provided: R1 may not be halogen when R2 and R3 are both halogen; R2 may not be 2-halogen when R3 is 4-halogen; or a pharmaceutically acceptable salt thereof; or formula II: whrein: R4 is selected from the group consisting of C1-C6 alkoxy, phosphonato, amino, sulfamyl, carboxy, acetoxy and dimethylamino (C2-C6 alkoxy); R6 is selected from the group consisting of nitro, hydrogen, phosphonato, amino, sulfamyl, carboxy, acetoxy and dimethylamino (C2-C6 alkoxy); and R7 is selected from the group consisting of halogen, C1-C6 alkoxy, C1-C6 alkyl, nitro, cyano, hydroxy, phosphonato, amino, sulfamyl, carboxy, acetoxy, dimethylamino (C2-C6 alkoxy) and trifluoromethyl; provided R5 and R6 may not be hydrogen in the same compound; or a pharmaceutically acceptable salt thereof.

  提供了一种类Utilizing the following formula: wherein: R1 is selected from the group consisting of halogen, C1-C6 alkoxy, nitro, phosphonato, amino, sulfamyl, carboxy, acetoxy and dimethylamino (C2-C6 alkoxy); and R2 and R3 are independently selected from the group consisting of halogen, C1-C6 alkoxy, C1-C6 alkyl, nitro, cyano, hydroxy, phosphonato, amino, sulfamyl, carboxy, acetoxy, and dimethylamino (C2-C6 alkoxy); provided: R1 may not be halogen when R2 and R3 are both halogen; R2 may not be 2-halogen when R3 is 4-halogen; or a pharmaceutically acceptable salt thereof; or formula II: wherein: R4 is selected from the group consisting of C1-C6 alkoxy, phosphonato, amino, sulfamyl, carboxy, acetoxy and dimethylamino (C2-C6 alkoxy); R6 is selected from the group consisting of nitro, hydrogen, phosphonato, amino, sulfamyl, carboxy, acetoxy and dimethylamino (C2-C6 alkoxy); and R7 is selected from the group consisting of halogen, C1-C6 alkoxy, C1-C6 alkyl, nitro, cyano, hydroxy, phosphonato, amino, sulfamyl, carboxy, acetoxy, dimethylamino (C2-C6 alkoxy) and trifluoromethyl; provided R5 and R6 may not be hydrogen in the same compound; or a pharmaceutically acceptable salt thereof.
• EP1305015A4
  申请人：——

  公开号：EP1305015A4

  公开（公告）日：2003-05-21