5-(4-氯苯基)-1H-吡咯并[2,3-b]吡啶 | 918516-27-5

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 5-(4-氯苯基)-1H-吡咯并[2,3-b]吡啶
• 中文别名: 5-(4-氯苯基)-7-氮杂吲哚
• 英文名称: 5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine
• CAS: 918516-27-5
• 化学式: C₁₃H₉ClN₂
• 分子量: 228.681
• InChiKey: AIRHBAXIGSQPNX-UHFFFAOYSA-N

物化性质

• 密度：
  1.326±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  5-(4-氯苯基)-1H-吡咯并[2,3-b]吡啶 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 碘 、 caesium carbonate 、 三乙胺 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Design of Novel 3-Pyrimidinylazaindole CDK2/9 Inhibitors with Potent In Vitro and In Vivo Antitumor Efficacy in a Triple-Negative Breast Cancer Model

  摘要：

  In the present study, a novel series of 3-pyrimidinylazaindoles were designed and synthesized using a bioinformatics strategy as cyclin-dependent kinases CDK2 and CDK9 inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription. The present approach gives new dimensions to the existing SAR and opens a new opportunity for the lead optimizations from comparatively inexpensive starting materials. The study led to the identification of the alternative lead candidate 4ab with a nanomolar potency against CDK2 and CDK9 and potent antiproliferative activities against a panel of tested tumor cell lines along with a better safety ratio of similar to 33 in comparison to reported leads. In addition, the identified lead 4ab demonstrated a good solubility and an acceptable in vivo PK profile. The identified lead 4ab showed an in vivo efficacy in mouse triple-negative breast cancer (TNBC) syngeneic models with a TGI (tumor growth inhibition) of 90% without any mortality growth inhibition in comparison to reported leads.

  DOI：

  10.1021/acs.jmedchem.7b00663
• 作为产物：
  描述：

  3-bromo-5-(4-chloro-phenyl)-pyridin-2-ylamine 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide potassium tert-butylate 、 四甲基胍 作用下， 以 N-甲基吡咯烷酮 、 甲苯 为溶剂， 反应 4.0h， 生成 5-(4-氯苯基)-1H-吡咯并[2,3-b]吡啶
  参考文献：
  名称：

  Novel Processes for the manufacture of Propane-1-sulfonic acid -amide

  摘要：

  根据本发明提供了制备化合物1的新工艺，以及用于这些工艺中的中间体和关键中间体的新合成路线。

  公开号：

  US20120022258A1
• 作为试剂：
  描述：

  5-(4-氯苯基)-1H-吡咯并[2,3-b]吡啶 、 N-(2,4-二氟-3-甲酰基苯基)-1-丙烷磺酰胺 在 5-(4-氯苯基)-1H-吡咯并[2,3-b]吡啶 作用下， 以44的产率得到propane-1-sulfonic acid (3-{[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-yl]hydroxymethyl}-2,4-difluorophenyl)amide
  参考文献：
  名称：

  Tetrahedron Lett. 2012, 53, 4161-4165

  摘要：

  DOI：

文献信息

• [EN] PROTEIN KINASE INHIBITORS FOR PROMOTING LIVER REGENERATION OR REDUCING OR PREVENTING HEPATOCYTE DEATH<br/>[FR] INHIBITEURS DE PROTÉINE KINASE POUR FAVORISER LA RÉGÉNÉRATION DU FOIE, OU POUR RÉDUIRE OU PRÉVENIR LA MORT DES HÉPATOCYTES
  申请人：HEPAREGENIX GMBH

  公开号：WO2018134254A1

  公开（公告）日：2018-07-26

  The invention relates to MKK4 (mitogen-activated protein kinase 4) and their use in promoting liver regeneration or reducing or preventing hepatocyte death. The MKK4 inhibitors selectively inhibit protein kinase MKK4 over protein kinases JNK and MKK7.

  这项发明涉及MKK4（有丝分裂原活化蛋白激酶4）及其在促进肝再生或减少或预防肝细胞死亡中的应用。这些MKK4抑制剂选择性地抑制蛋白激酶MKK4而不是蛋白激酶JNK和MKK7。
• [EN] PROTEIN KINASE INHIBITORS FOR PROMOTING LIVER REGENERATION OR REDUCING OR PREVENTING HEPATOCYTE DEATH<br/>[FR] INHIBITEURS DE PROTÉINE KINASE PERMETTANT DE FAVORISER LA RÉGÉNÉRATION DU FOIE, OU DE RÉDUIRE OU DE PRÉVENIR LA MORT DES HÉPATOCYTES
  申请人：HEPAREGENIX GMBH

  公开号：WO2020016243A1

  公开（公告）日：2020-01-23

  The invention relates to compounds of formula (I) which are inhibitors of MKK4 (mitogen-activated protein kinase kinase 4) and their use in promoting liver regeneration or reducing or preventing hepatocyte death. The compounds selectively inhibit protein kinase MKK4 over protein kinases JNK and MKK7. (I), wherein R x, R y , R z and R zz are selected from: a) R x and R y are F and R z and R zz are H; b) R x, R y and R zz are independently halogen and R z is H; c) R x R z and R zz are independently halogen and R y is H; and d) R x R y and R z are independently halogen and R zz is H

  该发明涉及式(I)的化合物，这些化合物是MKK4 (丝裂原活化蛋白激酶激酶4)的抑制剂，用于促进肝再生或减少或预防肝细胞死亡。这些化合物选择性地抑制蛋白激酶MKK4，而不影响蛋白激酶JNK和MKK7。(I)中，其中 Rx、Ry、Rz和Rzz从以下选项中选择：a) Rx和Ry为F，Rz和Rzz为H；b) Rx、Ry和Rzz独立为卤素，Rz为H；c) Rx、Rz和Rzz独立为卤素，Ry为H；以及d) Rx、Ry和Rz独立为卤素，Rzz为H。
• Synthesis and biological evaluation of selected 7-azaindole derivatives as CDK9/Cyclin T and Haspin inhibitors
  作者：Lianie Pieterse、Lesetja J. Legoabe、Richard M. Beteck、Béatrice Josselin、Stéphane Bach、Sandrine Ruchaud

  DOI：10.1007/s00044-020-02560-1

  日期：2020.8

  to its value in the design of inhibitors of diseases related protein kinases. However, this scaffold has not been evaluated against Haploid germ cell-specific nuclear protein kinase (Haspin). Herein, we report the synthesis of a select set of 7-azaindole derivatives and their evaluation against Haspin. The compounds were also evaluated against CDK9/Cyclin T kinase. The synthesis of 7-azaindole derivatives

  7-氮杂吲哚支架由于其在疾病相关蛋白激酶抑制剂设计中的价值而备受关注。但是，该支架尚未针对单倍体生殖细胞特异性核蛋白激酶（Haspin）进行评估。本文中，我们报告了一组7-氮杂吲哚衍生物的合成及其对Haspin的评价。还针对CDK9 /细胞周期蛋白T激酶评估了化合物。7-氮杂吲哚衍生物的合成是通过使用适当的卤代7-氮杂吲哚和硼酸的Suzuki偶联而实现的。所筛选的化合物中的七个在纳摩尔至低微摩尔范围内表现出作为CDK9 / Cyclin T和/或Haspin抑制剂的活性。最有前途的双重抑制化合物18c对CDK9 / Cyclin T的抑制潜力为0.206 µM，对Haspin的抑制潜力为0.118 µM。CDK9 /细胞周期蛋白T和Haspin的双重抑制可提供潜在的潜在抗有丝分裂剂，在进一步的抗癌研究中具有价值。
• Novel Processes for the manufacture of Propane-1-sulfonic acid -amide
  申请人：Brumsted Corey James

  公开号：US20120022258A1

  公开（公告）日：2012-01-26

  According to the present invention there are provided novel processes for the manufacture of the compound of formula 1 as well as intermediates and novel synthesis routes for key intermediates used in those processes.

  根据本发明提供了制备化合物1的新工艺，以及用于这些工艺中的中间体和关键中间体的新合成路线。
• COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR
  申请人：Spevak Wayne

  公开号：US20080167338A1

  公开（公告）日：2008-07-10

  Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

  描述了对蛋白激酶活性有作用的化合物，以及使用这些化合物来治疗与蛋白激酶异常活性相关的疾病和病况的方法。