9-methoxy-4-(2-methoxy-5-nitrophenyl)-4,5,6,10c-tetrahydro-3aH-pyrrolo[3,4-c]carbazole-1,3-dione | 622860-97-3

• 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: 9-methoxy-4-(2-methoxy-5-nitrophenyl)-4,5,6,10c-tetrahydro-3aH-pyrrolo[3,4-c]carbazole-1,3-dione
• CAS: 622860-97-3
• 化学式: C₂₂H₁₉N₃O₆
• 分子量: 421.409
• InChiKey: OSMHIHFTIIDAOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9-methoxy-4-(2-methoxy-5-nitrophenyl)-4,5,6,10c-tetrahydro-3aH-pyrrolo[3,4-c]carbazole-1,3-dione 在 盐酸 、 nickel boride 、 三溴化硼 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 4-(5-Amino-2-methoxyphenyl)-9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,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 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 环己烷 为溶剂， 反应 10.25h， 生成 9-methoxy-4-(2-methoxy-5-nitrophenyl)-4,5,6,10c-tetrahydro-3aH-pyrrolo[3,4-c]carbazole-1,3-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

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。
• ANTICANCER AGENT COMPOSITION
  申请人：Carna Biosciences, Inc.

  公开号：EP3100742A1

  公开（公告）日：2016-12-07

  Provided is a pharmaceutical composition comprising a Cdc7 inhibitor and an M phase promoter. In particular, the Cdc7 inhibitor contained in the pharmaceutical composition is a furanone derivative represented by formula (I), or a pharmaceutically acceptable salt thereof. (In the formula, A is -COOR1 or a hydrogen atom; R1 is a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocycle; R2 and R3 are the same or different and are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted phenyl group, an optionally substituted heterocycle, an optionally substituted heterocyclic condensed ring, or an optionally substituted amino group. Alternatively, R2 and R3 may, together with the nitrogen atoms bonding the same, form an optionally substituted heterocycle or optionally substituted heterocyclic condensed ring. R4 is a hydrogen atom or halogen atom. However, if A is -COOR1, R2 and R3 are not both simultaneously optionally substituted amino groups. When A is a hydrogen atom, R3 is a hydrogen atom.)

  本发明提供了一种药物组合物，其中包含一种 Cdc7 抑制剂和一种 M 期促进剂。特别是，药物组合物中所含的 Cdc7 抑制剂是由式（I）表示的呋喃酮衍生物或其药学上可接受的盐。(式中，A为-COOR1或氢原子；R1为氢原子、任选取代的烃基或任选取代的杂环；R2和R3相同或不同，各自为氢原子、任选取代的烃基、任选取代的苯基、任选取代的杂环、任选取代的杂环缩合环或任选取代的氨基。或者，R2 和 R3 可与结合在一起的氮原子一起形成任选取代的杂环或任选取代的杂环缩合环。R4 是氢原子或卤素原子。但是，如果 A 是-COOR1，R2 和 R3 不能同时是任选取代的氨基。当 A 为氢原子时，R3 为氢原子）。
• 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
• ANTICANCER AGENT COMPOSITION COMPRISING A CDC7 INHIBITOR AND A WEE1 INHIBITOR
  申请人：Carna Biosciences, Inc.

  公开号：EP3100742B1

  公开（公告）日：2020-05-20
• US7094798B1
  申请人：——

  公开号：US7094798B1

  公开（公告）日：2006-08-22