methyl 4-oxo-2,3,4,9-tetrahydro-1H-carbazole-5-carboxylate | 246513-42-8

• 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: methyl 4-oxo-2,3,4,9-tetrahydro-1H-carbazole-5-carboxylate
• 英文别名: methyl 5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate
• CAS: 246513-42-8
• 化学式: C₁₄H₁₃NO₃
• 分子量: 243.262
• InChiKey: YAQSQUUCVARXHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-oxo-2,3,4,9-tetrahydro-1H-carbazole-5-carboxylate 在 hydrazine hydrate 、 potassium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 10-(2-(dimethylamino)ethyl)-2,3,5,10-tetrahydro[1,2]diazepino[3,4,5,6-def]carbazol-6(1H)-one
  参考文献：
  名称：

  Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development

  摘要：

  Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses; therefore, this enzyme is targeted by PARP inhibitors in cancer therapy. Here we have developed a number of fused tetra- or pentacyclic dihydrodiazepinoindolone derivatives with excellent PARP enzymatic and cellular PARylation inhibition activities. These efforts led to the identification of pamiparib (BGB-290, 139), which displays excellent PARP-1 and PARP-2 inhibition with IC₅₀ of 1.3 and 0.9 nM, respectively. In a cellular PARylation assay, this compound inhibits PARP activity with IC₅₀ = 0.2 nM. Cocrystal of pamiparib shows similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a P-gp substrate and shows excellent drug metabolism and pharmacokinetics (DMPK) properties with significant brain penetration (17-19%, mice). The compound is currently being investigated in phase III clinical trials as a maintenance therapy in platinum-sensitive ovarian cancer and gastric cancer.

  DOI：

  10.1021/acs.jmedchem.0c01346
• 作为产物：
  描述：

  2-溴-3-硝基苯甲酸甲酯 在 二(氰基苯)二氯化钯 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 1,1'-双(二苯基膦)二茂铁 、 copper(l) iodide 、 1,10-菲罗啉 、 一氧化碳 、 1,3-双(二苯基膦)丙烷 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、607.95 kPa 条件下， 生成 methyl 4-oxo-2,3,4,9-tetrahydro-1H-carbazole-5-carboxylate
  参考文献：
  名称：

  Novel palladium-catalyzed synthesis of 1,2-dihydro-4(3H)-carbazolones

  摘要：

  Two sequential palladium-catalyzed reactions are the key steps in a novel synthetic route to carbazolones, an intermolecular Stille coupling followed by a recently developed palladium-catalyzed reductive N-heteroannulation. A number of functionalized 1,2-dihydro-4(3H)-carbazolones were prepared using this sequence. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)00072-2

文献信息

• Substituted tricyclics
  申请人：Eli Lilly and Company

  公开号：US06177440B1

  公开（公告）日：2001-01-23

  A class of novel tricyclics is disclosed together with the use of such compounds for inhibiting sPLA2 mediated release of fatty acids for treatment of conditions such as septic shock.

  一类新型三环化合物被披露，以及利用这类化合物抑制sPLA2介导的脂肪酸释放，用于治疗诸如感染性休克等疾病。
• 二氮杂*并咔唑类ido抑制剂及其应用
  申请人：南京众慧网络科技有限公司

  公开号：CN108794492A

  公开（公告）日：2018-11-13

  本发明属于化学医药领域，具体涉及二氮杂并咔唑类IDO抑制剂或其药学可接受的盐，以及含有这些化合物的药物组合物和这些化合物或组合物在药物制备中的应用，本发明提供的二氮杂并咔唑类IDO抑制剂，结构如式I所示，对IDO1和IDO2激酶具有较好的抑制活性，对结肠癌细胞具有较高的抑制活性。
• [EN] FUSED TETRA OR PENTA-CYCLIC DIHYDRODIAZEPINOCARBAZOLONES AS PARP INHIBITORS<br/>[FR] DIHYDRODIAZÉPINOCARBAZOLONES TÉTRA OU PENTACYCLIQUES FUSIONNÉS À UTILISER EN TANT QU'INHIBITEURS DE PARP
  申请人：BEIGENE LTD

  公开号：WO2013097225A1

  公开（公告）日：2013-07-04

  Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.

  提供了某些融合的四环或五环化合物及其盐、组合物和使用方法。
• FUSED TETRA OR PENTA-CYCLIC DIHYDRODIAZEPINOCARBAZOLONES AS PARP INHIBITORS
  申请人：BEIGENE, LTD.

  公开号：US20150175617A1

  公开（公告）日：2015-06-25

  Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.

  提供了某些融合的四环或五环化合物及其盐，以及它们的组合物和使用方法。
• Substituted carbazoles as inhibitors of spla2
  申请人：——

  公开号：US20040087796A1

  公开（公告）日：2004-05-06

  Carbazoles of formula (I) with R 2 =hydroxyfunctional amide (hydroxamic or esters) are disclosed together with the use of such compounds for inhibiting sPLA 2 mediated release of fatty acids for treatment of conditions such as septic shock. 1

  公式(I)中的Carbazoles，其中R2为羟基官能化酰胺（羟肟酰胺或酯）被揭示出来，以及使用这些化合物来抑制sPLA2介导的脂肪酸释放，以治疗诸如脓毒性休克等疾病。