ethyl 2-((3-fluoro-4-methylphenyl)amino)-2-oxoacetate | 69066-06-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 2-((3-fluoro-4-methylphenyl)amino)-2-oxoacetate
• 英文别名: Ethyl [(3-fluoro-4-methylphenyl)amino](oxo)acetate；ethyl 2-(3-fluoro-4-methylanilino)-2-oxoacetate
• CAS: 69066-06-4
• 化学式: C₁₁H₁₂FNO₃
• 分子量: 225.22
• InChiKey: UXBJCBOMHDIITG-UHFFFAOYSA-N

物化性质

• 密度：
  1.254±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-((3-fluoro-4-methylphenyl)amino)-2-oxoacetate 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 N¹-(3-fluoro-4-methylphenyl)-N²-((5-(2-hydroxyethyl)-4-methylthiazol-2-yl)(piperidin-2-yl)methyl)oxalamide hydrochloride
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of Entry Inhibitors That Target the CD4-Binding Site of HIV-1

  摘要：

  The CD4 binding site on HIV-1 gp120 has been validated as a drug target to prevent HIV-1 entry to cells. Previously, we identified two small molecule inhibitors consisting of a 2,2,6,6-tetramethylpiperidine ring linked by an oxalamide to a p-halide-substituted phenyl group, which target this site, specifically, a cavity termed "Phe43 cavity". Here we use synthetic chemistry, functional assessment, and structure-based analysis to explore variants of each region of these inhibitors for improved antiviral properties. Alterations of the phenyl group and of the oxalamide linker indicated that these regions were close to optimal in the original lead compounds. Design of a series of compounds, where the tetramethylpiperidine ring was replaced with new scaffolds, led to improved antiviral activity. These new scaffolds provide insight into the surface chemistry at the entrance of the cavity and offer additional opportunities by which to optimize further these potential-next-generation therapeutics and microbicides against HIV-1.

  DOI：

  10.1021/jm3002247
• 作为产物：
  描述：

  3-氟-4-甲基苯胺 、 草酰氯单乙酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 ethyl 2-((3-fluoro-4-methylphenyl)amino)-2-oxoacetate
  参考文献：
  名称：

  发现硬脂酰辅酶A去饱和酶的细胞色素P450 4F11激活的抑制剂。

  摘要：

  硬脂酰辅酶A去饱和酶（SCD）催化饱和脂肪酸向不饱和脂肪酸转化的第一步。膜完整性和细胞增殖需要不饱和脂肪酸。由于这些原因，SCD抑制剂代表了潜在的癌症治疗方法。但是，具有内在活性的SCD抑制剂会导致皮肤毒性，这对它们的发展构成了障碍。我们最近描述了一系列草酸二酰胺，它们通过CYP4F11介导的代谢转化为癌症子集内的活性SCD抑制剂。在本文中，我们描述了草酸二酰胺和相关N-酰基脲的优化，以及与代谢活化和SCD抑制有关的结构-活性关系的分析。

  DOI：

  10.1021/acs.jmedchem.8b00052

文献信息

• CD4 mimics as HIV entry inhibitors: Lead optimization studies of the aromatic substituents
  作者：Tetsuo Narumi、Hiroshi Arai、Kazuhisa Yoshimura、Shigeyoshi Harada、Yuki Hirota、Nami Ohashi、Chie Hashimoto、Wataru Nomura、Shuzo Matsushita、Hirokazu Tamamura

  DOI：10.1016/j.bmc.2013.02.041

  日期：2013.5

  Several CD4 mimics have been reported as HIV-1 entry inhibitors that can intervene in the interaction between a viral envelope glycoprotein gp120 and a cell surface protein CD4. Our previous SAR studies led to a finding of a highly potent analogue 3 with bulky hydrophobic groups on a piperidine moiety. In the present study, the aromatic ring of 3 was modified systematically in an attempt to improve

  据报道，有几种CD4模拟物是HIV-1进入抑制剂，它们可以干预病毒包膜糖蛋白gp120与细胞表面蛋白CD4之间的相互作用。我们以前的SAR研究导致发现了高效有效的类似物3，在哌啶部分带有大量疏水基团。在本研究中，系统地修饰了3的芳香环，以试图改善其抗病毒活性和CD4模仿性，从而诱导gp120的构象变化，从而使包膜对中和抗体更加敏感。合成化合物的生物学分析表明，氟基团作为间位基团的引入芳环的取代基引起抗HIV活性的增加和CD4拟态的增强，并导致新型化合物13a的抗HIV活性是3的两倍，甚至在CD4拟态上也有显着提高在较低的浓度。
• TBAI-Catalyzed S–H and N–H Insertion Reactions of α-Diazoesters with Thiophenols and Amines under Metal-Free Conditions
  作者：Rongxiang Chen、Guoyang Ma、Yawen Li、Jinju Zhang、Ran Xia、Kai-Kai Wang、Lantao Liu

  DOI：10.1021/acs.joc.2c01262

  日期：2022.8.19

  Mild, convenient, and effective TBAI-catalyzed S–H and N–H insertion reactions of α-diazoesters with thiophenols and aromatic amines under metal-free conditions have been described, furnishing a straightforward and general platform for the synthesis of various thioethers and 2-amino-2-oxoacetates in moderate to excellent yields. Moreover, this strategy features simple operation, mild conditions, broad

  已经描述了在无金属条件下温和、方便和有效的 TBAI 催化的 α-重氮酯与苯硫酚和芳香胺的 S-H 和 N-H 插入反应，为合成各种硫醚和 2 -amino-2-oxoacetates，产率适中至极好。此外，该策略具有操作简单、条件温和、底物范围广、易于放大等特点。
• Design, Synthesis, and Antiviral Activity of Entry Inhibitors That Target the CD4-Binding Site of HIV-1
  作者：Francesca Curreli、Spreeha Choudhury、Ilya Pyatkin、Victor P. Zagorodnikov、Anna Khulianova Bulay、Andrea Altieri、Young Do Kwon、Peter D. Kwong、Asim K. Debnath

  DOI：10.1021/jm3002247

  日期：2012.5.24

  The CD4 binding site on HIV-1 gp120 has been validated as a drug target to prevent HIV-1 entry to cells. Previously, we identified two small molecule inhibitors consisting of a 2,2,6,6-tetramethylpiperidine ring linked by an oxalamide to a p-halide-substituted phenyl group, which target this site, specifically, a cavity termed "Phe43 cavity". Here we use synthetic chemistry, functional assessment, and structure-based analysis to explore variants of each region of these inhibitors for improved antiviral properties. Alterations of the phenyl group and of the oxalamide linker indicated that these regions were close to optimal in the original lead compounds. Design of a series of compounds, where the tetramethylpiperidine ring was replaced with new scaffolds, led to improved antiviral activity. These new scaffolds provide insight into the surface chemistry at the entrance of the cavity and offer additional opportunities by which to optimize further these potential-next-generation therapeutics and microbicides against HIV-1.
• Discovery of Cytochrome P450 4F11 Activated Inhibitors of Stearoyl Coenzyme A Desaturase
  作者：Sarah E. Winterton、Emanuela Capota、Xiaoyu Wang、Hong Chen、Prema L. Mallipeddi、Noelle S. Williams、Bruce A. Posner、Deepak Nijhawan、Joseph M. Ready

  DOI：10.1021/acs.jmedchem.8b00052

  日期：2018.6.28

  Stearoyl-CoA desaturase (SCD) catalyzes the first step in the conversion of saturated fatty acids to unsaturated fatty acids. Unsaturated fatty acids are required for membrane integrity and for cell proliferation. For these reasons, inhibitors of SCD represent potential treatments for cancer. However, systemically active SCD inhibitors result in skin toxicity, which presents an obstacle to their development

  硬脂酰辅酶A去饱和酶（SCD）催化饱和脂肪酸向不饱和脂肪酸转化的第一步。膜完整性和细胞增殖需要不饱和脂肪酸。由于这些原因，SCD抑制剂代表了潜在的癌症治疗方法。但是，具有内在活性的SCD抑制剂会导致皮肤毒性，这对它们的发展构成了障碍。我们最近描述了一系列草酸二酰胺，它们通过CYP4F11介导的代谢转化为癌症子集内的活性SCD抑制剂。在本文中，我们描述了草酸二酰胺和相关N-酰基脲的优化，以及与代谢活化和SCD抑制有关的结构-活性关系的分析。