ethyl 4-(1H-benzo[d][1,2,3]triazol-1-yl)-4-oxobutanoate | 1333146-96-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并三唑类
• 英文名称: ethyl 4-(1H-benzo[d][1,2,3]triazol-1-yl)-4-oxobutanoate
• 英文别名: Ethyl 4-(1h-1,2,3-benzotriazol-1-yl)-4-oxobutanoate；ethyl 4-(benzotriazol-1-yl)-4-oxobutanoate
• CAS: 1333146-96-5
• 化学式: C₁₂H₁₃N₃O₃
• 分子量: 247.254
• InChiKey: NBQVPTYWIZCYAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  74.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-甲氧基-联苯-4-基)-乙酮 、 ethyl 4-(1H-benzo[d][1,2,3]triazol-1-yl)-4-oxobutanoate 在 magnesium bromide ethyl etherate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以3.2 g的产率得到ethyl (Z)-4-hydroxy-6-(4'-methoxy-[1,1'-biphenyl]-4-yl)-6-oxohex-4-enoate
  参考文献：
  名称：

  Irreversible inhibitors of pyruvate kinase M2 and the use thereof

  摘要：

  这项发明提供了一类新型的基于丙炔酰胺的PKM2不可逆抑制剂化合物，其一般化学式为I，以及诱导受患肿瘤的对象产生抗肿瘤效果的方法，包括向该对象投与包含化合物I有效量的药物组合物的药物组合物。

  公开号：

  US20210221801A1
• 作为产物：
  描述：

  T406石油添加剂 、 丁二酸单乙酯酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 ethyl 4-(1H-benzo[d][1,2,3]triazol-1-yl)-4-oxobutanoate
  参考文献：
  名称：

  Irreversible inhibitors of pyruvate kinase M2 and the use thereof

  摘要：

  这项发明提供了一类新型的基于丙炔酰胺的PKM2不可逆抑制剂化合物，其一般化学式为I，以及诱导受患肿瘤的对象产生抗肿瘤效果的方法，包括向该对象投与包含化合物I有效量的药物组合物的药物组合物。

  公开号：

  US20210221801A1

文献信息

• [EN] INTEGRIN-LINKED KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE LIÉE À L'INTÉGRINE
  申请人：UNIV OHIO STATE RES FOUND

  公开号：WO2012071310A1

  公开（公告）日：2012-05-31

  A number of compounds and use of the compounds in a method for treating or preventing cancer in a subject by administering to the subject a pharmaceutical composition including a compound of formula (I) or a pharmaceutically acceptable salt thereof are described. The compounds can also be used to inhibit integrin-linked kinase in a cell, which has an effect on the Akt signaling pathway.

  描述了一种化合物的数量以及在治疗或预防受试者癌症的方法中通过向受试者施用包括式（I）化合物或其药用可接受盐的药物组合物来使用这些化合物。这些化合物还可以用于抑制细胞中的整合素相关激酶，从而影响Akt信号通路。
• AMIDE INHIBITORS OF RENIN
  申请人：Gant Thomas G.

  公开号：US20100124550A1

  公开（公告）日：2010-05-20

  The present invention relates to new amide inhibitors of renin, pharmaceutical compositions thereof, and methods of use thereof

  本发明涉及新的肾素酶抑制剂酰胺、其药物组成以及使用方法。
• A Biocatalytic Route to Highly Enantioenriched β-Hydroxydioxinones
  作者：Rick C. Betori、Eric R. Miller、Karl A. Scheidt

  DOI：10.1002/adsc.201700095

  日期：2017.4.3

  A novel biocatalytic system to access a wide variety of β‐hydroxydioxinones from β‐ketodioxinones employing commercial engineered ketoreductases has been developed. This practical system provides a remarkably straightforward solution to limitations in accessing certain chemical scaffolds common in β‐hydroxydioxinones that are of great interest due to their diversification capabilities. A few highlights

  已经开发出一种新型生物催化系统，可使用商业工程酮还原酶从 β-酮二恶酮中获取多种 β-羟基二恶酮。这个实用的系统为获取β-羟基二恶英酮中常见的某些化学支架的限制提供了一种非常简单的解决方案，这些化学支架由于其多样化能力而备受关注。该系统的一些亮点是它具有高产率、高对映选择性且无需色谱法。我们展示了广泛的基质范围和高度的可扩展性。
• Identification and Characterization of a Novel Integrin-Linked Kinase Inhibitor
  作者：Su-Lin Lee、En-Chi Hsu、Chih-Chien Chou、Hsiao-Ching Chuang、Li-Yuan Bai、Samuel K. Kulp、Ching-Shih Chen

  DOI：10.1021/jm2007744

  日期：2011.9.22

  Integrin-linked kinase (ILK) represents a relevant target for cancer therapy in light of its role in promoting oncogenesis and tumor progression. Through the screening of an in-house focused compound library, we identified N-methyl-3-(1-(4-(piperazin-1-yl)phenyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-3-yl)propanamide (22) as a novel ILK inhibitor (IC50, 0.6 mu M), which exhibited high in vitro potency against a panel of prostate and breast cancer cell lines (IC50, 1-2.5 mu M), while normal epithelial cells were unaffected. Compound 22 facilitated the dephosphorylation of Akt at Ser-473 and other ILK targets, including glycogen synthase kinase-3 beta and myosin light chain. Moreover, 22 suppressed the expression of the transcription/translation factor YB-1 and its targets HER2 and EGFR in PC-3 cells, which could be rescued by the stable expression of constitutively active ILK. Evidence indicates that 22 induced autophagy and apoptosis, both of which were integral to its antiproliferative activity. Together, this broad spectrum of mechanisms underlies the therapeutic potential of 22 in cancer treatment, which is manifested by its in vivo efficacy as a single oral agent in suppressing PC-3 xenograft tumor growth.
• Development of Novel Irreversible Pyruvate Kinase M2 Inhibitors
  作者：I-Shan Hsieh、Balraj Gopula、Chi-Chi Chou、Hsiang-Yi Wu、Geen-Dong Chang、Wen-Jin Wu、Chih-Shiang Chang、Po-Chen Chu、Ching S. Chen

  DOI：10.1021/acs.jmedchem.9b00763

  日期：2019.9.26

  As cancer cells undergo metabolic reprogramming in the course of tumorigenesis, targeting energy metabolism represents a promising strategy in cancer therapy. Among various metabolic enzymes examined, pyruvate kinase M2 type (PKM2) has received much attention in light of its multifaceted function in promoting tumor growth and progression. In this study, we reported the development of a novel irreversible inhibitor of PKM2, compound 1, that exhibits a differential tumor-suppressive effect among an array of cancer cell lines. We further used a clickable activity-based protein profiling (ABPP) probe and SILAC coupled with LC-MS/MS to identify the Cys-317 and Cys-326 residues of PKM2 as the covalent binding sites. Equally important, compound 1 at 10 mg/kg was effective in suppressing xenograft tumor growth in nude mice without causing acute toxicity by targeting both metabolic and oncogenic functions. Together, these data suggest its translational potential to foster new strategies for cancer therapy.