1-(4-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethenone | 944956-37-0

• 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
• 英文名称: 1-(4-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethenone
• 英文别名: 3-acetyl-4-phenyl-1H-pyrrolo[2,3-b]pyridine；1-(4-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone
• CAS: 944956-37-0
• 化学式: C₁₅H₁₂N₂O
• 分子量: 236.273
• InChiKey: FKGARMNFEGUUFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethenone 在 三乙胺 、 二异丙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.25h， 生成 3-oxo-3-(4-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)propyl (pyridin-3-ylmethyl)carbamodithioate
  参考文献：
  名称：

  Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors

  摘要：

  Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.03.003
• 作为产物：
  描述：

  苯硼酸 在 aluminum (III) chloride 、 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate 、 caesium carbonate 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 12.5h， 生成 1-(4-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethenone
  参考文献：
  名称：

  Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors

  摘要：

  Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.03.003

文献信息

• PYRROLO[2,3-B]PYRIDINE COMPOUNDS, AZAINDOLE COMPOUNDS USED FOR SYNTHESIZING SAID PYRROLO[2,3-B]PYRIDINE COMPOUNDS, METHODS FOR THE PRODUCTION THEREOF, AND USES THEREOF
  申请人：Meijer Laurent

  公开号：US20100184790A1

  公开（公告）日：2010-07-22

  The invention relates to pyrrolo[2,3-b]pyridine compounds and azaindole compounds used for the synthesis thereof. The invention also relates to methods for the production thereof and the uses thereof. Said novel pyrrolo[2,3-b]pyridine compounds according to the invention have great antiproliferative, apoptotic, and neuroprotective activities. The invention particularly applies to the pharmaceutical field.

  该发明涉及用于合成吡咯并[2,3-b]吡啶化合物和氮杂吲哚化合物的方法。该发明还涉及其生产方法和用途。根据该发明，所述新型吡咯并[2,3-b]吡啶化合物具有很强的抗增殖、凋亡和神经保护活性。该发明特别适用于药物领域。
• Fused heterobicyclic kinase inhibitors
  申请人：Arnold D. Lee

  公开号：US20070208053A1

  公开（公告）日：2007-09-06

  Compounds of the formula and pharmaceutically acceptable salts thereof, wherein X 1 , X 2 , X 3 , X 4 , X 5 , X 5 , X 7 , R 1 , and Q 1 are defined herein, inhibit kinase enzymes and are useful for the treatment and/or prevention of hyperproliferative diseases such as cancer. The compounds are also useful in the treatment of inflammation, allergy, asthma, disease and conditions of the immune system, disease and conditions of the nervous system, cardiovascular diseases, disease and conditions of the eye, dermatological diseases, osteoporosis, diabetes, multiple sclerosis, and infections.

  该式化合物及其药物可接受的盐，其中X1、X2、X3、X4、X5、X5、X7、R1和Q1在此被定义，可抑制激酶酶，并且可用于治疗和/或预防过度增殖性疾病，如癌症。这些化合物还可用于治疗炎症、过敏、哮喘、免疫系统疾病和情况、神经系统疾病和情况、心血管疾病、眼部疾病和情况、皮肤病、骨质疏松症、糖尿病、多发性硬化症和感染。
• FUSED HETEROBICYCLIC KINASE INHIBITORS
  申请人：OSI Pharmaceuticals, Inc.

  公开号：EP1979353A2

  公开（公告）日：2008-10-15
• COMPOSES PYRROLO[2,3-B]PYRIDINE, COMPOSES AZAINDOLES UTILES DANS LA SYNTHESE DE CES COMPOSES PYRROLO[2,3-B]PYRIDINE, LEURS PROCEDES DE FABRICATION ET LEURS UTILISATIONS
  申请人：Centre National de la Recherche Scientifique

  公开号：EP2125803B1

  公开（公告）日：2013-04-10
• [EN] FUSED HETEROBICYCLIC KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE HETEROBICYCLIQUES FUSIONNES
  申请人：OSI PHARMACEUTICAL INC

  公开号：WO2007084667A2

  公开（公告）日：2007-07-26

  [EN] Compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein X₁, X₂, X₃, X₄, X₅, X₆, X₇, R¹, and Q¹ are defined herein, inhibit kinase enzymes and are useful for the treatment and/or prevention of hyperproliferative diseases such as cancer. The compounds are also useful in the treatment of inflammation, allergy, asthma, disease and conditions of the immune system, disease and conditions of the nervous system, cardiovascular diseases, disease and conditions of the eye, dermatological diseases, osteoporosis, diabetes, multiple sclerosis, and infections.
  [FR] La présente invention concerne des composés répondant à la formule (I) et des sels pharmaceutiquement acceptables, dans laquelle X₁, X₂, X₃, X₄, X₅, X₆, X₇, R¹ et Q¹ sont définis dans le présent document, qui inhibent des enzymes kinase et sont utiles dans le traitement et/ou la prophylaxie de pathologies hyperprolifératives, telles qu'un cancer. Les composés sont également utiles dans le traitement d'une inflammation, d'une allergie, de l'asthme, d'une pathologie et d'affections du système immunitaire, de pathologies et d'affections du système nerveux, de cardiopathies, de maladies et affections ophtalmiques, de pathologies dermatologiques, de l'ostéoporose, de diabètes, de la sclérose en plaque et d'infections.