2-((3-chloro-4-fluorophenyl)amino)-2-oxoacetic acid | 740870-86-4

• 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: 2-((3-chloro-4-fluorophenyl)amino)-2-oxoacetic acid
• 英文别名: 2-(3-Chloro-4-fluoroanilino)-2-oxoacetic acid
• CAS: 740870-86-4
• 化学式: C₈H₅ClFNO₃
• mdl: MFCD04045724
• 分子量: 217.584
• InChiKey: OJUWBNZOUDHLMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-((3-chloro-4-fluorophenyl)amino)-2-oxoacetic acid 、 2-(2-(amino(piperidin-2-yl)methyl)-4-methylthiazol-5-yl)ethan-1-ol 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 盐酸 作用下， 以35%的产率得到N¹-(3-chloro-4-fluorophenyl)-N²-((5-(2-hydroxyethyl)-4-methylthiazol-2-yl)(piperidin-2-yl)methyl)oxalamide dihydrochloride
  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：

  ethyl 3'-chloro-4'-fluorooxanilate 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 2-((3-chloro-4-fluorophenyl)amino)-2-oxoacetic acid
  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

文献信息

• [EN] SUBSTITUTED ISOQUINOLINYLMETHYL AMIDES, ANALOGUES THEREOF, AND METHODS USING SAME<br/>[FR] AMIDES D'ISOQUINOLINYLMÉTHYLE SUBSTITUÉS, ANALOGUES DE CEUX-CI ET PROCÉDÉS LES UTILISANT
  申请人：ARBUTUS BIOPHARMA CORP

  公开号：WO2021250461A1

  公开（公告）日：2021-12-16

  The present disclosure includes substituted isoquinolinylmethyl amides, or analogues thereof, of formula (I), wherein the groups R1, R2, R3, R4a, R4b and R5 and variable p are as defined herein, and compositions comprising the same, that can be used to treat, ameliorate and/or prevent hepatitis B virus (HBV) and/or hepatitis D virus (HDV) infections in a patient.

  本公开涵盖了式(I)的取代异喹啉甲基酰胺或其类似物，其中所述的基团R1、R2、R3、R4a、R4b和R5以及变量p的定义如本文所述，并包括含有这些物质的组合物，可用于治疗、改善和/或预防患者体内的乙型肝炎病毒（HBV）和/或丙型肝炎病毒（HDV）感染。
• 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.