ethyl 2-amino-1H-pyrrolo[2,3-c]pyridine-3-carboxylate | 1096472-13-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: ethyl 2-amino-1H-pyrrolo[2,3-c]pyridine-3-carboxylate
• CAS: 1096472-13-7
• 化学式: C₁₀H₁₁N₃O₂
• 分子量: 205.216
• InChiKey: DVJKNZIXDVKKAD-UHFFFAOYSA-N

物化性质

• 熔点：
  151-153 °C(Solvent: Ethanol)
• 沸点：
  431.9±40.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  81
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-amino-1H-pyrrolo[2,3-c]pyridine-3-carboxylate 在 sodium nitrite 、 sodium carbonate 作用下， 以 水 、 溶剂黄146 为溶剂， 生成 2-diazo-3-ethoxycarbonylpyrrolo[2,3-c]pyridine
  参考文献：
  名称：

  三氮杂氮杂吲哚的合成：一类具有抗肿瘤活性的新三氮烯

  摘要：

  尽管在癌症的治疗和预防方面有所改善，但新诊断的数量仍在继续增加。这激发了人们对开发新型有效化疗药物的浓厚兴趣。三氮烯类化合物（例如达卡巴嗪）已用于许多癌症类型的临床管理，包括脑癌，白血病和黑色素瘤。为了鉴定新的抗增殖剂，合成了带有三氮杂氮杂吲哚骨架的新的化合物类别。化合物5 -克和6 - ç筛选针对人肿瘤细胞系组成的小组，其中两个，图5e和5f中，表现出细胞毒性（GI 50范围：2.2-8.2μM）在所有细胞系中。这两种化合物甚至在某些具有多重耐药性的细胞系中都保持了细胞毒性。流式细胞仪分析表明它们具有通过溶酶体参与凋亡诱导细胞死亡的能力。

  DOI：

  10.1002/cmdc.201100027
• 作为产物：
  描述：

  ethyl-2-cyano-2-(3-nitropyrid-4-yl)acetate 在 锌 氮 、 溶剂黄146 、 碳酸氢钠 作用下， 以 溶剂黄146 为溶剂， 反应 1.33h， 以to give the title compound (2.02 g, 93%)的产率得到ethyl 2-amino-1H-pyrrolo[2,3-c]pyridine-3-carboxylate
  参考文献：
  名称：

  9H-PYRIMIDO[4,5-B]INDOLES, 9H-PYRIDO[4',3':4,5]PYRROLO[2,3-D]PYRIDINES, AND 9H 1,3,6,9 TETRAAZA-FLUORENES AS CHK1 KINASE FUNCTION INHIBITORS

  摘要：

  本发明涉及治疗化合物领域，更具体地涉及某些三环化合物（在此称为TC化合物），特别是某些9H-嘧啶并[4,5-b]吲哚，9H-吡啶[4′，3′：4,5]吡咯[2,3-d]吡啶和9H-1,3,6,9-四氮杂芴化合物，它们可以抑制检查点激酶1（CHK1）激酶功能。本发明还涉及包含这些化合物的制药组合物，以及在体内外使用这些化合物和组合物来抑制CHK1激酶功能，以及治疗由CHK1介导，通过抑制CHK1激酶功能得到改善等疾病和病况，包括增生性疾病如癌症等，可选地与另一种制剂联合使用，例如（a）DNA拓扑异构酶I或II抑制剂;（b）DNA损伤剂;（c）抗代谢物或TS抑制剂;（d）微管靶向剂;和（e）电离辐射。

  公开号：

  US20100210639A1

文献信息

• Synthesis and Cytotoxic and Antiviral Activity Profiling of All‐Four Isomeric Series of Pyrido‐Fused 7‐Deazapurine Ribonucleosides
  作者：Lucia Veselovská、Natálie Kudlová、Soňa Gurská、Barbora Lišková、Martina Medvedíková、Ondřej Hodek、Eva Tloušťová、Nemanja Milisavljevic、Michal Tichý、Pavla Perlíková、Helena Mertlíková‐Kaiserová、Jana Trylčová、Radek Pohl、Blanka Klepetářová、Petr Džubák、Marián Hajdúch、Michal Hocek

  DOI：10.1002/chem.202001124

  日期：2020.10.9

  synthesized. The total synthesis of each isomeric fused heterocycle through multistep heterocyclization was followed by glycosylation and derivatization at position 4 by cross‐coupling reactions or nucleophilic substitutions. All compounds were tested for cytostatic and antiviral activity. The most active were pyrido[4′,3′:4,5]pyrimidine nucleosides bearing MeO, NH2, MeS, or CH3 groups at position 4, which

  设计并合成了在不同位置具有吡啶氮原子的新颖的4个取代的吡啶基融合的7个氮杂嘌呤核糖核苷的所有四个异构体系列。通过多步杂环化，每个异构体稠合杂环的总合成，然后通过交叉偶联反应或亲核取代在位置4进行糖基化和衍生化。测试所有化合物的细胞抑制活性和抗病毒活性。活性最高的是带有MeO，NH 2，MeS或CH 3的吡啶并[4'，3'：4,5]嘧啶核苷在位置4的基团中，它们显示出亚微摩尔的细胞毒性作用和对癌细胞的良好选择性。该机制涉及通过磷酸化激活并掺入DNA，其中修饰的核糖核苷的存在导致双链断裂和凋亡。
• [EN] 9H-PYRIMIDO[4,5-B]INDOLES, 9H-PYRIDO[4',3':4,5]PYRROLO[2,3-D]PYRIDINES, AND 9H-1,3,6,9-TETRAAZA-FLUORENES AS CHK1 KINASE FUNCTION INHIBITORS<br/>[FR] 9H-PYRIMIDO[4,5-B]INDOLES, 9H-PYRIDO[4',3':4,5]PYRROLO[2,3-D]PYRIDINES, ET 9H-1,3,6,9-TÉTRAAZA-FLUORÈNES EN TANT QU'INHIBITEURS DE LA FONCTION KINASE CHK1
  申请人：CANCER REC TECH LTD

  公开号：WO2009004329A1

  公开（公告）日：2009-01-08

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain tricyclic compounds (referred to herein as TC compounds), and especially certain 9H-pyrimido[4,5-b]indole, 9H-pyrido[4',3':4,5]pyrrolo[2,3-d)pyridine, and 9H-1,3,6,9-tetraaza-fluorene compounds, which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or Il inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

  本发明一般涉及治疗化合物领域，更具体地涉及某些三环化合物（在此称为TC化合物），特别是某些9H-嘧啶并[4,5-b]吲哚，9H-吡啶并[4'，3'：4,5]吡咯[2,3-d]吡啶和9H-1,3,6,9-四氮杂芴化合物，这些化合物等等，能够抑制检查点激酶1（CHK1）激酶功能。本发明还涉及包含这些化合物的药物组合物，以及在体内外使用这些化合物和组合物来抑制CHK1激酶功能，并用于治疗由CHK1介导的疾病和症状，通过抑制CHK1激酶功能改善的疾病和症状等，包括癌症等增殖性疾病，可选地与另一药剂结合，例如，（a）DNA拓扑异构酶I或II抑制剂；（b）DNA损伤剂；（c）抗代谢物或TS抑制剂；（d）微管靶向剂；和（e）电离辐射。
• 9H-pyrimido[4,5-B]indoles, 9H-pyrido[4',3':4,5]pyrrolo[2,3-D]pyridines, and 9H 1,3,6,9 tetraaza-fluorenes as CHK1 kinase function inhibitors
  申请人：Collins Ian

  公开号：US08618121B2

  公开（公告）日：2013-12-31

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain tricyclic compounds (referred to herein as TC compounds), and especially certain 9H-pyrimido[4,5-b]indole, 9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyridine, and 9H-1,3,6,9-tetraaza-fluorene compounds, which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

  本发明涉及治疗化合物领域，更具体地涉及某些三环化合物（在此称为TC化合物），特别是某些9H-嘧啶并[4,5-b]吲哚，9H-吡啶[4'，3'：4,5]吡咯[2,3-d]吡啶和9H-1,3,6,9-四氮杂芴化合物，它们可以抑制检查点激酶1（CHK1）的激酶功能。本发明还涉及包含这种化合物的药物组合物，以及使用这种化合物和组合物在体内外抑制CHK1激酶功能，并用于治疗由CHK1介导的疾病和病症，通过抑制CHK1激酶功能而得到改善，等等，包括增殖性疾病如癌症等，可选择与另一种药物一起使用，例如（a）DNA拓扑异构酶I或II抑制剂；（b）DNA损伤剂；（c）抗代谢物或TS抑制剂；（d）微管靶向剂；和（e）电离辐射。
• Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing
  作者：John C. Reader、Thomas P. Matthews、Suki Klair、Kwai-Ming J. Cheung、Jane Scanlon、Nicolas Proisy、Glynn Addison、John Ellard、Nelly Piton、Suzanne Taylor、Michael Cherry、Martin Fisher、Kathy Boxall、Samantha Burns、Michael I. Walton、Isaac M. Westwood、Angela Hayes、Paul Eve、Melanie Valenti、Alexis de Haven Brandon、Gary Box、Rob L. M. van Montfort、David H. Williams、G. Wynne Aherne、Florence I. Raynaud、Suzanne A. Eccles、Michelle D. Garrett、Ian Collins

  DOI：10.1021/jm2007326

  日期：2011.12.22

  Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.
• 9H-PYRIMIDO[4,5-B]INDOLES, 9H-PYRIDO[4',3':4,5]PYRROLO[2,3-D]PYRIDINES, AND 9H-1,3,6,9-TETRAAZA-FLUORENES AS CHK1 KINASE FUNCTION INHIBITORS
  申请人：Cancer Research Technology Limited

  公开号：EP2170886A1

  公开（公告）日：2010-04-07