benzyl 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazole-4-carboxylate | 622860-29-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: benzyl 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazole-4-carboxylate
• 英文别名: benzyl 9-methoxy-1,3-dioxo-6H-pyrrolo[3,4-c]carbazole-4-carboxylate
• CAS: 622860-29-1
• 化学式: C₂₃H₁₆N₂O₅
• 分子量: 400.39
• InChiKey: NYXGQTFGNPEYBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  97.5
• 氢给体数：
  2
• 氢受体数：
  5

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	benzyl 9-methoxy-1,3-dioxo-1,2,3,3a,4,5,6,10c-octahydropyrrolo[3,4-c]carbazole-4-carboxylate	622860-27-9	C23H20N2O5	404.422

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazole-4-carboxylic acid	622860-31-5	C16H10N2O5	310.266
  ——	4-amino-9-methoxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	622860-34-8	C15H11N3O3	281.271
  ——	9-hydroxy-4-iodopyrrolo[3,4-c]carbazole-1,3(1H,6H)-dione	622860-38-2	C14H7IN2O3	378.126
  ——	9-Hydroxy-4-(3-methoxyphenyl)pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	622860-48-4	C21H14N2O4	358.353
  ——	9-hydroxy-4-(4-hydroxymethylphenyl)pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	——	C21H14N2O4	358.353
  ——	9-hydroxy-4-(4-methoxyphenyl)pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	622860-47-3	C21H14N2O4	358.353
  ——	9-Hydroxy-4-(3-hydroxymethyl-phenyl)-6H-pyrrolo[3,4-c]carbazole-1,3-dione	——	C21H14N2O4	358.353
  ——	9-hydroxy-4-(2-methoxyphenyl)pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	——	C21H14N2O4	358.353
  ——	9-hydroxy-4-p-tolyl-6H-pyrrolo[3,4-c]carbazole-1,3-dione	——	C21H14N2O3	342.354
  ——	4-(9-hydroxy-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo[3,4-c]carbazol-4-yl)-benzonitrile	——	C21H11N3O3	353.337

反应信息

• 作为反应物：
  描述：

  benzyl 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazole-4-carboxylate 在 palladium on activated charcoal 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 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 19.3h， 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 在 manganese(IV) oxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 benzyl 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazole-4-carboxylate
  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

文献信息

• [EN] INHIBITORS OF CHECKPOINT KINASES (WEE1 AND CHK1)<br/>[FR] INHIBITEURS DE CHECKPOINT KINASES (WEE1 ET CHK1)
  申请人：WARNER LAMBERT CO

  公开号：WO2003091255A1

  公开（公告）日：2003-11-06

  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，其中所述衍生物特异性地抑制检查点激酶Wee1和Chk1中的一个或两个。
• 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。
• INHIBITORS OF CHECKPOINT KINASES (WEE1 AND CHK1)
  申请人：WARNER-LAMBERT COMPANY LLC

  公开号：EP1501831A1

  公开（公告）日：2005-02-02
• US7094798B1
  申请人：——

  公开号：US7094798B1

  公开（公告）日：2006-08-22
• 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.