1-(6-溴咪唑并[1,2-A]吡啶-3-基)乙酮 | 30493-41-5

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 中文名称: 1-(6-溴咪唑并[1,2-A]吡啶-3-基)乙酮
• 英文名称: 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)ethanone
• 英文别名: 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)ethan-1-one
• CAS: 30493-41-5
• 化学式: C₉H₇BrN₂O
• 分子量: 239.071
• InChiKey: DDVXKYXTMIQMPV-UHFFFAOYSA-N

物化性质

• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  34.4
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P330,P363,P501
• 危险性描述：
  H302,H312,H332
• 储存条件：
  存储条件：2-8°C，需密封并保持干燥。

反应信息

• 作为反应物：
  描述：

  1-(6-溴咪唑并[1,2-A]吡啶-3-基)乙酮 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 5.5h， 生成 6-bromo-3-(1H-pyrazol-3-yl)imidazo[1,2-a]pyridine
  参考文献：
  名称：

  Synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel PI3 kinase p110α inhibitors

  摘要：

  3-{1-[(4-Fluorophenyl)sulfonyl]-1H-pyrazol-3-yl}-2-methylimidazo[1,2-a]pyridine, 2a, was discovered in our chemical library as a novel p110 alpha inhibitor with an IC50 of 0.67 mu M, through screening in a scintillation proximity assay. Optimization of the substituents of 2a increased the p110 alpha inhibitory activity by more than 300-fold (2g: IC50 = 0.0018 mu M). Further structural modification of 2g afforded thiazole derivative 12, which has potent p110 alpha inhibitory activity (IC50 of 0.0028 mu M) and is highly selective for p110 alpha over other PI3K isoforms. Compound 12 also inhibited serum-induced cell proliferation of A375 and HeLa cells in vitro with IC50 values of 0.14 mu M and 0.21 mu M, respectively, and suppressed tumor growth by 37% in a mouse HeLa xenograft model when dosed intraperitoneally at 25 mg/kg. These results suggest that selective p110 alpha inhibitors may have potential as cancer therapeutic agents. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.047
• 作为产物：
  描述：

  (E)-N'-(5-bromopyridin-2-yl)-N,N-dimethylformimidamide 、 一氯丙酮 在 碳酸氢钠 作用下， 以 异丙醇 为溶剂， 反应 12.0h， 以1.0 g的产率得到1-(6-溴咪唑并[1,2-A]吡啶-3-基)乙酮
  参考文献：
  名称：

  [EN] 2,3-DISUBSTITUTED PYRIDINE COMPOUNDS AS TGF-BETA INHIBITORS AND METHODS OF USE
  [FR] COMPOSÉS DE PYRIDINE 2,3-DISUBSTITUÉS UTILISÉS COMME INHIBITEURS DE TGF-BÊTA ET PROCÉDÉS D'UTILISATION

  摘要：

  本发明涉及的化合物包括公式（IV）的化合物，以及一种治疗癌症的方法，包括向患有癌症的受试者施用其中一种化合物，结合另一种癌症治疗方法。这些化合物（IV）抑制TGF-β超家族成员如Nodal或Activin的信号传导。

  公开号：

  WO2015157093A1

文献信息

• [EN] ALKYNYL ALCOHOLS AS KINASE INHIBITORS<br/>[FR] ALCOOLS D'ALCYNYLE UTILISÉS COMME INHIBITEURS DE KINASES
  申请人：AMGEN INC

  公开号：WO2009158011A1

  公开（公告）日：2009-12-30

  Selected compounds are effective for prophylaxis and treatment of inflammation and inflammatory disorders, such as NIK-mediated disorders. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, inflammation and the like.

  选定的化合物对预防和治疗炎症和炎症性疾病，如NIK介导的疾病，具有有效性。该发明涵盖了新颖的化合物、类似物、前药及其药用可接受的盐，以及用于预防和治疗涉及炎症等疾病和其他疾病或病症的药物组合物和方法。
• Design and Synthesis of Imidazopyridine Analogues as Inhibitors of Phosphoinositide 3-Kinase Signaling and Angiogenesis
  作者：Okseon Kim、Yujeong Jeong、Hyunseung Lee、Sun-Sun Hong、Sungwoo Hong

  DOI：10.1021/jm101582z

  日期：2011.4.14

  Phosphatidylinositol 3-kinase α (PI3Kα) is an important regulator of intracellular signaling pathways, controlling remarkably diverse arrays of physiological processes. Because the PI3K pathway is frequently up-regulated in human cancers, the inhibition of PI3Kα can be a promising approach to cancer therapy. In this study, we have designed and synthesized a new series of imidazo[1,2-a]pyridine derivatives

  磷脂酰肌醇3-激酶α（PI3Kα）是细胞内信号通路的重要调节剂，可控制多种多样的生理过程。由于PI3K途径在人类癌症中经常被上调，因此PI3Kα的抑制可能是一种有前途的癌症治疗方法。在本研究中，我们通过片段增长策略设计并合成了一系列新的咪唑并[1,2- a ]吡啶衍生物作为PI3Kα抑制剂。通过改变咪唑[1,2- a]的3和6位上的基团]吡啶，我们研究了结构活性关系（SAR）谱，并鉴定了一系列有效的PI3Kα抑制剂。代表性衍生物在细胞增殖和凋亡测定中显示出良好的活性。而且，这些抑制剂表现出值得注意的抗血管生成活性。
• [EN] DERIVATIVES OF 4-(IMIDAZO[1,2-A]PYRIDIN-3-YL)-N-(PYRIDIN-3-YL) PYRIMIDIN-2- AMINE FOR TREATING PROLIFERATIVE DISEASES AND CONDITIONS<br/>[FR] DÉRIVÉS DE 4-(IMIDAZO[1,2-A] PYRIDIN-3-YL)-N-(PYRIDIN-3-YL)PYRIMIDIN-2-AMINE POUR LE TRAITEMENT DE MALADIES ET D'AFFECTIONS PROLIFÉRATIVES
  申请人：AUCENTRA THERAPEUTICS PTY LTD

  公开号：WO2021072475A1

  公开（公告）日：2021-04-22

  A novel class of heteroaryl compounds for use in the prevention and/or treatment of proliferative diseases and conditions including cancers. The compounds are considered to be capable of inhibiting cell proliferation by inhibiting the activity of one or more protein kinases selected from CDKs such as CDK2, CDK4, CDK6 and/or CDK9, and/or other protein kinases such as FLT3 and its mutants. The compounds have the general structure I: (I)

  一类新型的杂环芳基化合物，用于预防和/或治疗包括癌症在内的增殖性疾病和症状。这些化合物被认为能够通过抑制细胞增殖来抑制细胞蛋白激酶的活性，所选的蛋白激酶包括CDKs（如CDK2、CDK4、CDK6和/或CDK9）以及其他蛋白激酶，如FLT3及其突变体。这些化合物具有一般结构I：（I）
• [EN] DERIVATIVES OF 4-(IMIDAZO[L,2-A]PYRIDIN-3-YL)-N-(PYRIDINYL)PYRIMIDIN- 2-AMINE AS THERAPEUTIC AGENTS<br/>[FR] DÉRIVÉS DE 4-(IMIDAZO [L, 2-A] PYRIDINE-3-YL)-N-(PYRIDINYL) PYRIMIDINE-2-AMINE EN TANT QU'AGENTS THÉRAPEUTIQUES
  申请人：AUCENTRA THERAPEUTICS PTY LTD

  公开号：WO2021003517A1

  公开（公告）日：2021-01-14

  A novel class of heteroaryl compounds for use in the prevention and/or treatment of proliferative diseases and conditions including cancers. The compounds are considered to be capable of inhibiting cell proliferation by inhibiting the activity of FLT3 and its mutant forms and/or other protein kinases such as CDKs. The compounds have the general structure I:

  一类新型的杂环芳基化合物，用于预防和/或治疗包括癌症在内的增生性疾病和症状。这些化合物被认为能够通过抑制FLT3及其突变形式和/或其他蛋白激酶如CDK的活性来抑制细胞增殖。这些化合物具有一般结构I：
• Inhibiting NF-κB-inducing kinase (NIK): Discovery, structure-based design, synthesis, structure–activity relationship, and co-crystal structures
  作者：Kexue Li、Lawrence R. McGee、Ben Fisher、Athena Sudom、Jinsong Liu、Steven M. Rubenstein、Mohmed K. Anwer、Timothy D. Cushing、Youngsook Shin、Merrill Ayres、Fei Lee、John Eksterowicz、Paul Faulder、Bohdan Waszkowycz、Olga Plotnikova、Ellyn Farrelly、Shou-Hua Xiao、Guoqing Chen、Zhulun Wang

  DOI：10.1016/j.bmcl.2013.01.012

  日期：2013.3

  The discovery, structure-based design, synthesis, and optimization of NIK inhibitors are described. Our work began with an HTS hit, imidazopyridinyl pyrimidinamine 1. We utilized homology modeling and conformational analysis to optimize the indole scaffold leading to the discovery of novel and potent conformationally constrained inhibitors such as compounds 25 and 28. Compounds 25 and 31 were co-crystallized

  介绍了NIK抑制剂的发现，基于结构的设计，合成和优化。我们的工作始于HTS热门产品，咪唑并吡啶基嘧啶胺1。我们利用同源性建模和构象分析来优化吲哚骨架，从而导致发现新颖而有效的构象受限抑​​制剂，例如化合物25和28。化合物25和31与NIK激酶结构域共结晶以提供结构见解。