methyl 2-(4-(trifluoromethyl)pyridin-2-yl)acetate | 1612222-96-4

• 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: methyl 2-(4-(trifluoromethyl)pyridin-2-yl)acetate
• 英文别名: methyl 2-[4-(trifluoromethyl)-2-pyridyl]acetate；Methyl 2-(4-(trifluoromethyl)pyridin-2-yl)acetate；methyl 2-[4-(trifluoromethyl)pyridin-2-yl]acetate
• CAS: 1612222-96-4
• 化学式: C₉H₈F₃NO₂
• 分子量: 219.163
• InChiKey: VKMZYIHZDPAGAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-(trifluoromethyl)pyridin-2-yl)acetate 在 氨 作用下， 以 甲醇 为溶剂， 反应 21.0h， 生成 2-(4-(trifluoromethyl)pyridin-2-yl)acetamide
  参考文献：
  名称：

  Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties

  摘要：

  Inhibition of glutaminase-1 (GLS-1) hampers the proliferation of tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused on optimizing physicochemical and pharmacokinetic properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials. Compound 27 attains high oral exposures in preclinical species, with strong in vivo target engagement, and should robustly inhibit glutaminase in humans.

  DOI：

  10.1021/acs.jmedchem.0c01398
• 作为产物：
  描述：

  diethyl 2-(4-(trifluoromethyl)pyridin-2-yl)malonate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以66%的产率得到methyl 2-(4-(trifluoromethyl)pyridin-2-yl)acetate
  参考文献：
  名称：

  Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties

  摘要：

  Inhibition of glutaminase-1 (GLS-1) hampers the proliferation of tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused on optimizing physicochemical and pharmacokinetic properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials. Compound 27 attains high oral exposures in preclinical species, with strong in vivo target engagement, and should robustly inhibit glutaminase in humans.

  DOI：

  10.1021/acs.jmedchem.0c01398

文献信息

• Expedient Synthesis of α-(2-Azaheteroaryl) Acetates via the Addition of Silyl Ketene Acetals to Azine-<i>N</i>-oxides
  作者：Allyn T. Londregan、Kristen Burford、Edward L. Conn、Kevin D. Hesp

  DOI：10.1021/ol501359r

  日期：2014.6.20

  A new and expedient synthesis of α-(2-azaheteroaryl) acetates is presented. The reaction proceeds rapidly under mild conditions via the addition of silyl ketene acetals to azine-N-oxides in the presence of the phosphonium salt PyBroP. This procedure affords diverse α-(2-azaheteroaryl) acetates which are highly desirable components/building blocks in molecules of pharmaceutical interest but are traditionally

  提出了一种新的方便合成α-（2-氮杂杂环芳基）乙酸酯的方法。在mild盐PyBroP存在下，通过将甲硅烷基烯酮缩醛添加到嗪-N-氧化物中，该反应在温和条件下快速进行。该方法提供了多种α-（2-氮杂杂环芳基）乙酸酯，它们是药物感兴趣的分子中非常需要的组分/结构单元，但是传统上难以通过现代方法合成。描述了反应的优化和机理，以及新型的电子增强的PyBroP衍生物。
• Potent and selective inhibitors of receptor-interacting protein kinase 1 that lack an aromatic back pocket group
  作者：Gregory L. Hamilton、Huifen Chen、Gauri Deshmukh、Charles Eigenbrot、Rina Fong、Adam Johnson、Pawan Bir Kohli、Patrick J. Lupardus、Bianca M. Liederer、Sreemathy Ramaswamy、Haowei Wang、Jian Wang、Zhaowu Xu、Yunliang Zhu、Domagoj Vucic、Snahel Patel

  DOI：10.1016/j.bmcl.2019.04.014

  日期：2019.6

  lipophilic aromatic group present in most literature inhibitors that typically occupies a hydrophobic back pocket of the protein active site. Despite not having this ubiquitous feature of many known RIPK1 inhibitors, we were able to obtain compounds with good potency, kinase selectivity, and pharmacokinetic properties in rats. The use of the lipophilic yet metabolically stable pentafluoroethyl group was critical

  受体相互作用蛋白激酶1（RIPK1），细胞坏死病途径的关键组成部分，已被公认是重要的治疗靶点。RIPK1的药理抑制或遗传失活已在动物疾病模型中显示出了希望，这些疾病的范围包括急性缺血性疾病，慢性炎症和神经退行性疾病。我们在这里介绍一类RIPK1抑制剂，其特征是大多数文献中的抑制剂（通常占据蛋白质活性位点的疏水性后口袋）中缺乏亲脂性芳香族基团。尽管没有许多已知的RIPK1抑制剂普遍存在的功能，我们仍能够在大鼠中获得具有良好效价，激酶选择性和药代动力学特性的化合物。
• 1-HETEROCYCLYL-1,5-DIHYDRO-PYRAZOLO[3,4-D] PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS PDE9A MODULATORS
  申请人：GIOVANNINI Riccardo

  公开号：US20140073641A1

  公开（公告）日：2014-03-13

  The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones, wherein i.) the nitrogen atom of the pyrazolo-group that is next to the pyrimidino-group is attached to a non-aromatic, organic heterocycle having at least one ring hetero atom selected from O, N and S and ii.) to the C-atom between the two nitrogen atoms of the pyrimidinone-ring a second substituent is bound via an optionally substituted methylene-bridge. According to one aspect of the invention the new compounds are for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments for the treatment of Alzheimer's disease.

  本发明涉及新型1,6-二取代吡唑嘧啶酮，其中i)紧邻嘧啶基的吡唑环上的氮原子连接到至少具有一个O、N和S中的环异构原子的非芳香性有机杂环上，ii)通过可选取代的亚甲基桥连接到嘧啶酮环的两个氮原子之间的C原子上的第二个取代基。根据本发明的一个方面，新化合物用于制造药物，特别是用于治疗感知、注意力、学习或记忆缺陷的药物。新化合物还用于制造治疗阿尔茨海默病的药物。
• GLS1 INHIBITORS FOR TREATING DISEASE
  申请人：Board of Regents, The University of Texas System

  公开号：US20160009704A1

  公开（公告）日：2016-01-14

  Disclosed herein are compounds and compositions useful in the treatment of GLS1 mediated diseases, such as cancer, having the structure of Formula I: Methods of inhibition GLS1 activity in a human or animal subject are also provided.

  本文揭示了一些化合物和组合物，其结构公式为I，可用于治疗GLS1介导的疾病，如癌症。还提供了抑制人类或动物主体中GLS1活性的方法。
• HETEROCYCLIC GLS1 INHIBITORS
  申请人：Board of Regents, The University of Texas System

  公开号：EP3677579A1

  公开（公告）日：2020-07-08

  Disclosed herein are compounds and compositions useful in the treatment of GLS I mediated diseases, such as cancer, having the structure of Formula I. Methods of inhibition GLS I activity in a human or animal subject are also provided.

  本文公开了用于治疗 GLS I 介导的疾病（如癌症）的具有式 I 结构的化合物和组合物。还提供了抑制人或动物体内 GLS I 活性的方法。