4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione | 374068-99-2

• 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: 4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione
• 英文别名: CEP-A；1,2,3,11-Tetrahydro-5,11-diaza-benzo[a]trindene-4,6-dione；9,19-diazapentacyclo[10.7.0.02,6.07,11.013,18]nonadeca-1(12),2(6),7(11),13,15,17-hexaene-8,10-dione
• CAS: 374068-99-2
• 化学式: C₁₇H₁₂N₂O₂
• 分子量: 276.294
• InChiKey: UYZYLAFMPDNCIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  62
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione 在 sodium hydride 、 N-甲基吗啉 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 盐酸 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 、 1,4-二氧六环 为溶剂， 反应 2.0h， 以65%的产率得到9-(2-Aminoacetyl)-9,19-diazapentacyclo[10.7.0.02,6.07,11.013,18]nonadeca-1(12),2(6),7(11),13,15,17-hexaene-8,10-dione;hydrochloride
  参考文献：
  名称：

  Serendipitous Discovery of a Prodrug of a PARP-1 Inhibitor

  摘要：

  During SAR development of previously reported pyrrolocarbazole 1, a potent PARP‐1 inhibitor, compound 14, was discovered serendipitously to be a prodrug of compound 1.

  DOI：

  10.1111/cbdd.12165
• 作为产物：
  描述：

  1-(1H-indol-2-yl)cyclopentan-1-ol 在 盐酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel poly(ADP-ribose) polymerase-1 inhibitors

  摘要：

  A series of novel pyrrolocarbazoles was synthesized as potential PARP-1 inhibitors. Pyrrolocarbazole 1 was identified as a potent PARP-I inhibitor (IC50 = 36 nM) from our internal database. Synthesis of analogs around this template with the aid of modeling studies led to the identification of the truncated imide 14. Compound 14 (IC50 = 40 nM), with deleted B-ring, was found to be an equipotent PARP-1 inhibitor. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.099

文献信息

• Efficient Synthesis of Maleimides and Carbazoles via Zn(OTf)₂-Catalyzed Tandem Annulations of Isonitriles and Allenic Esters
  作者：Yuanzhen Li、Haixia Zou、Jianxian Gong、Jing Xiang、Tuoping Luo、Junmin Quan、Guoxin Wang、Zhen Yang

  DOI：10.1021/ol7018086

  日期：2007.9.1

  Lewis acid Zn(OTf)(2)-catalyzed tandem annulations of isonitriles and allenic esters which lead to efficient and flexible syntheses of a range of biologically significant maleimides and carbazoles and related compounds are reported. A mechanistic rationale is proposed to account for the observed reactivity.
• Novel poly(ADP-ribose) polymerase-1 inhibitors
  作者：Derek Dunn、Jean Husten、Mark A. Ator、Sankar Chatterjee

  DOI：10.1016/j.bmcl.2006.10.010

  日期：2007.1

  Synthesis and activity of a series of 4-thiazol-yl substituted analogs of novel pyrrolocarbazole 1 as poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been disclosed. (c) 2006 Elsevier Ltd. All rights reserved.
• Poly(ADP-ribose) polymerase-1 activity facilitates the dissociation of nuclear proteins from platinum-modified DNA
  作者：Evan R. Guggenheim、Alison E. Ondrus、Mohammad Movassaghi、Stephen J. Lippard

  DOI：10.1016/j.bmc.2008.09.074

  日期：2008.12

  The affinity of the poly(ADP-ribose) polymerase-1 (PARP-1) for platinum-damaged DNA was first discovered during photo-cross-linking experiments using the photoactive compound Pt-BP6 [J. Am. Chem. Soc. 2004, 126, 6536-6537], an analogue of the anticancer drug cis-diamminedichloroplatinum(II), cisplatin. Although PARP inhibitors sensitize cancer cells to cisplatin, there are conflicting reports in the literature about their efficacy. In order to improve our understanding of the mechanism by which PARP inhibition might potentiate the cell-killing ability of cisplatin, and to shed light on the source of the discrepancy among different laboratories, we have in the present study probed the influence of three PARP inhibitors in four types of cancer cells, cervical ( HeLa), testicular (NTera2), pancreatic (BxPC3), and osteosarcoma (U2OS), on the results of Pt-BP6 photo-cross-linking experiments and cytotoxicity assays. We find that the activity of PARP proteins following exposure to platinum-modified DNA results in the dissociation of DNA-bound proteins. PARP inhibitors were able to sensitize some, but not all, of the cell lines to cisplatin. This cell line-dependence and the potential consequences of PARP-initiated protein removal from platinum-DNA lesions are discussed. Control experiments revealed that NTera2 cells are especially sensitive to PARP inhibition. (C) 2008 Elsevier Ltd. All rights reserved.
• CYCLOALKANOPYROLOCARBAZOLE DERIVATIVES AND THE USE THEREOF AS PARP, VEGFR2 AND MLK3 INHIBITORS
  申请人：CEPHALON, INC.

  公开号：EP2066324B1

  公开（公告）日：2013-05-29
• Synthesis and structure–activity relationships of novel poly(ADP-ribose) polymerase-1 inhibitors
  作者：Ming Tao、Chung Ho Park、Ron Bihovsky、Gregory J. Wells、Jean Husten、Mark A. Ator、Robert L. Hudkins

  DOI：10.1016/j.bmcl.2005.10.099

  日期：2006.2

  A series of novel pyrrolocarbazoles was synthesized as potential PARP-1 inhibitors. Pyrrolocarbazole 1 was identified as a potent PARP-I inhibitor (IC50 = 36 nM) from our internal database. Synthesis of analogs around this template with the aid of modeling studies led to the identification of the truncated imide 14. Compound 14 (IC50 = 40 nM), with deleted B-ring, was found to be an equipotent PARP-1 inhibitor. (c) 2005 Elsevier Ltd. All rights reserved.