4-(2-Chlorophenyl)-8-[3-(dimethylamino)propoxy]-9-hydroxy-6-methylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione | 622856-94-4

• 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: 4-(2-Chlorophenyl)-8-[3-(dimethylamino)propoxy]-9-hydroxy-6-methylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
• 英文别名: 4-(2-chlorophenyl)-8-[3-(dimethylamino)propoxy]-9-hydroxy-6-methylpyrrolo[3,4-c]carbazole-1,3-dione
• CAS: 622856-94-4
• 化学式: C₂₆H₂₄ClN₃O₄
• 分子量: 477.947
• InChiKey: ZWRDUCSPTGMSHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(2-Chlorophenyl)-8-[3-(dimethylamino)propoxy]-9-methoxy-6-methylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 4-(2-Chlorophenyl)-8-[3-(dimethylamino)propoxy]-9-hydroxy-6-methylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
  参考文献：
  名称：

  Synthesis and structure–activity relationships of soluble 8-substituted 4-(2-chlorophenyl)-9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of the Wee1 and Chk1 checkpoint kinases

  摘要：

  Pyrrolo[3,4-c]carbazoles bearing solubilising basic side chains at the 8-position retain potent Weel and Chk1 inhibitory properties in isolated enzyme assays, and evidence of G2/M checkpoint abrogation in several cellular assays. Co-crystal structure studies confirm that the primary binding to the Weel enzyme is as described previously, with the C-8 side chains residing in an area of bulk tolerance. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.12.046

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。
• Modified Wee1, crystals of peptide: inhibitor complexes containing such modified Wee1, and methods of use thereof
  申请人：Baker Neill Edward

  公开号：US20050037476A1

  公开（公告）日：2005-02-17

  Modified Wee1 peptides, polynucleotides encoding those peptides, and methods for purifying the peptides and crystallizing them as peptide: inhibitor complexes have been discovered. The three-dimensional structure of Wee1, including the ATP substrate binding site, and uses of this information in the design and screening of compounds that may associate with Wee1, or peptides structurally related thereto, have also been discovered.

  已经发现了修饰的 Wee1 肽、编码这些肽的多核苷酸以及纯化这些肽并将其结晶为肽：抑制剂复合物的方法。此外，还发现了 Wee1 的三维结构，包括 ATP 底物结合位点，以及利用这些信息设计和筛选可能与 Wee1 结合的化合物或与之结构相关的多肽的方法。
• 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
• Synthesis and structure–activity relationships of soluble 8-substituted 4-(2-chlorophenyl)-9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of the Wee1 and Chk1 checkpoint kinases
  作者：Jeff B. Smaill、Ho H. Lee、Brian D. Palmer、Andrew M. Thompson、Christopher J. Squire、Edward N. Baker、R. John Booth、Alan Kraker、Ken Hook、William A. Denny

  DOI：10.1016/j.bmcl.2007.12.046

  日期：2008.2

  Pyrrolo[3,4-c]carbazoles bearing solubilising basic side chains at the 8-position retain potent Weel and Chk1 inhibitory properties in isolated enzyme assays, and evidence of G2/M checkpoint abrogation in several cellular assays. Co-crystal structure studies confirm that the primary binding to the Weel enzyme is as described previously, with the C-8 side chains residing in an area of bulk tolerance. (C) 2007 Elsevier Ltd. All rights reserved.