benzyl (2E)-3-(5-methoxy-1H-indol-2-yl)-2-propenoate | 622860-26-8

• 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: benzyl (2E)-3-(5-methoxy-1H-indol-2-yl)-2-propenoate
• 英文别名: benzyl (E)-3-(5-methoxy-1H-indol-2-yl)prop-2-enoate
• CAS: 622860-26-8
• 化学式: C₁₉H₁₇NO₃
• 分子量: 307.349
• InChiKey: OKWNAYHJXUXVIU-JXMROGBWSA-N

物化性质

• 熔点：
  155-157 °C
• 沸点：
  513.8±40.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl (2E)-3-(5-methoxy-1H-indol-2-yl)-2-propenoate 在 palladium on activated charcoal manganese(IV) oxide 、 硫酸 、 二苯基膦叠氮化物 、 氢气 、 吡啶盐酸盐 、 三乙胺 、 叔丁醇 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 3.0~200.0 ℃ 、413.68 kPa 条件下， 反应 24.3h， 生成 9-hydroxy-4-iodopyrrolo[3,4-c]carbazole-1,3(1H,6H)-dione
  参考文献：
  名称：

  4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution

  摘要：

  High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]carbazole- 1,3(2H,6H)-dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2'-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.

  DOI：

  10.1021/jm0512591
• 作为产物：
  描述：

  5-甲氧基-1H-吲哚-2-羧酸 、 (苄氧羰基亚甲基)三苯基膦 在 甲醇 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以to give benzyl (2E)-3-(5-methoxy-1H-indol-2-yl)-2-propenoate (2) in a 30.46 g, 87% yield as pale yellow plates的产率得到benzyl (2E)-3-(5-methoxy-1H-indol-2-yl)-2-propenoate
  参考文献：
  名称：

  Inhibitors of checkpoint kinases (Wee1 and Chk1)

  摘要：

  本发明涉及公式I中的吡咯烷并咔唑衍生物，其中R1、R2、R7、R8、R9、X和Y如规范中所定义，其中这些衍生物特异性抑制检查点激酶Wee1和Chk1中的一个或两个。

  公开号：

  US07094798B1

文献信息

• Inhibitors of checkpoint kinases (Wee1 and Chk1)
  申请人：Pfizer Inc

  公开号：US07094798B1

  公开（公告）日：2006-08-22

  This invention relates to pyrrolocarbazole derivatives according formula I wherein R1, R2, R7, R8, R9, X and Y are as defined in the specification wherein said derivatives specifically inhibit one or both of the checkpoint kinases Wee1 and Chk1

  本发明涉及公式I中的吡咯烷并咔唑衍生物，其中R1、R2、R7、R8、R9、X和Y如规范中所定义，其中这些衍生物特异性抑制检查点激酶Wee1和Chk1中的一个或两个。
• 4-Phenylpyrrolo[3,4-<i>c</i>]carbazole-1,3(2<i>H</i>,6<i>H</i>)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution
  作者：Brian D. Palmer、Andrew M. Thompson、R. John Booth、Ellen M. Dobrusin、Alan J. Kraker、Ho H. Lee、Elizabeth A. Lunney、Lorna H. Mitchell、Daniel F. Ortwine、Jeff B. Smaill、Leesa M. Swan、William A. Denny

  DOI：10.1021/jm0512591

  日期：2006.8.1

  High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]carbazole- 1,3(2H,6H)-dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2'-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.