diethyl (((3-(trifluoromethyl)phenyl)carbonyl)amino)propanedioate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: diethyl (((3-(trifluoromethyl)phenyl)carbonyl)amino)propanedioate
• 英文别名: Diethyl 2-[[3-(trifluoromethyl)benzoyl]amino]propanedioate
• 化学式: C₁₅H₁₆F₃NO₅
• 分子量: 347.291
• InChiKey: AILUNOWQTGCRRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  diethyl (((3-(trifluoromethyl)phenyl)carbonyl)amino)propanedioate 在 吡啶 、 tetraphosphorus decasulfide 、 乙醇 、 sodium 作用下， 反应 4.17h， 生成 5-methyl-2-(3-trifluoromethylphenyl)thiazolo[5,4-d]pyrimidin-7-one
  参考文献：
  名称：

  Exploring the 7-oxo-thiazolo[5,4-d]pyrimidine core for the design of new human adenosine A3 receptor antagonists. Synthesis, molecular modeling studies and pharmacological evaluation

  摘要：

  A new series of 5-methyl-thiazolo[5,4-d]pyrimidine-7-ones bearing different substituents at position 2 (aryl, heteroaryl and arylamino groups) was synthesized and evaluated in radioligand binding assays to determine their affinities at the human (h) A(1), A(2A), and A(3) adenosine receptors (ARs). Efficacy at the hA(2B) and antagonism of selected ligands at the hA(3) were also assessed through cAMP experiments. Some of the new derivatives exhibited good to high hA(3)AR affinity and selectivity versus all the other AR subtypes. Compound 2-(4-chlorophenyl)-5-methyl-thiazolo[5,4-d]pyrimidine-7-one 4 was found to be the most potent and selective ligand of the series (K-i hA(3) = 18 nM). Molecular docking studies of the reported derivatives were carried out to depict their hypothetical binding mode in our hA(3) receptor model. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.010
• 作为产物：
  描述：

  氨基丙二酸二乙酯盐酸盐 、 3-(三氟甲基)苯甲酰氯 在 碳酸氢钠 作用下， 以 乙醚 、 水 为溶剂， 反应 2.0h， 以91%的产率得到diethyl (((3-(trifluoromethyl)phenyl)carbonyl)amino)propanedioate
  参考文献：
  名称：

  Exploring the 7-oxo-thiazolo[5,4-d]pyrimidine core for the design of new human adenosine A3 receptor antagonists. Synthesis, molecular modeling studies and pharmacological evaluation

  摘要：

  A new series of 5-methyl-thiazolo[5,4-d]pyrimidine-7-ones bearing different substituents at position 2 (aryl, heteroaryl and arylamino groups) was synthesized and evaluated in radioligand binding assays to determine their affinities at the human (h) A(1), A(2A), and A(3) adenosine receptors (ARs). Efficacy at the hA(2B) and antagonism of selected ligands at the hA(3) were also assessed through cAMP experiments. Some of the new derivatives exhibited good to high hA(3)AR affinity and selectivity versus all the other AR subtypes. Compound 2-(4-chlorophenyl)-5-methyl-thiazolo[5,4-d]pyrimidine-7-one 4 was found to be the most potent and selective ligand of the series (K-i hA(3) = 18 nM). Molecular docking studies of the reported derivatives were carried out to depict their hypothetical binding mode in our hA(3) receptor model. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.010

文献信息

• Electrochemical Synthesis of Unnatural Amino Acids via Anodic Decarboxylation of <i>N</i>-Acetylamino Malonic Acid Derivatives
  作者：Olesja Koleda、Katrina Prane、Edgars Suna

  DOI：10.1021/acs.orglett.3c02687

  日期：2023.11.10

  α-disubstituted cyclic amino acid derivatives in medicinal chemistry urges for analogue design with improved pharmacokinetic properties. Herein, we disclose an electrochemical approach toward unnatural THF- and THP-containing amino acid derivatives that relies on anodic decarboxylation-intramolecular etherification of inexpensive and readily available N-acetylamino malonic acid monoesters under Hofer–Moest

  α,α-二取代环状氨基酸衍生物在药物化学中的广泛应用迫切需要具有改进的药代动力学特性的类似物设计。在此，我们公开了一种针对非天然含THF和THP的氨基酸衍生物的电化学方法，该方法依赖于廉价且容易获得的N-乙酰氨基丙二酸单酯在Hofer-Moest反应条件下的阳极脱羧-分子内醚化。脱羧环化在恒定电流条件下在未分裂的细胞中在水性介质中进行，无需添加任何碱。在组织蛋白酶 K 抑制剂 balicatib 中，用含 THP 的氨基酸支架成功生物等排取代 1-氨基环己烷-1-羧酸亚基，有助于降低亲脂性，同时保留低纳摩尔酶抑制效力和相当的微粒体稳定性。
• Exploring the 7-oxo-thiazolo[5,4-d]pyrimidine core for the design of new human adenosine A3 receptor antagonists. Synthesis, molecular modeling studies and pharmacological evaluation
  作者：Flavia Varano、Daniela Catarzi、Lucia Squarcialupi、Marco Betti、Fabrizio Vincenzi、Annalisa Ravani、Katia Varani、Diego Dal Ben、Ajiroghene Thomas、Rosaria Volpini、Vittoria Colotta

  DOI：10.1016/j.ejmech.2015.04.010

  日期：2015.5

  A new series of 5-methyl-thiazolo[5,4-d]pyrimidine-7-ones bearing different substituents at position 2 (aryl, heteroaryl and arylamino groups) was synthesized and evaluated in radioligand binding assays to determine their affinities at the human (h) A(1), A(2A), and A(3) adenosine receptors (ARs). Efficacy at the hA(2B) and antagonism of selected ligands at the hA(3) were also assessed through cAMP experiments. Some of the new derivatives exhibited good to high hA(3)AR affinity and selectivity versus all the other AR subtypes. Compound 2-(4-chlorophenyl)-5-methyl-thiazolo[5,4-d]pyrimidine-7-one 4 was found to be the most potent and selective ligand of the series (K-i hA(3) = 18 nM). Molecular docking studies of the reported derivatives were carried out to depict their hypothetical binding mode in our hA(3) receptor model. (C) 2015 Elsevier Masson SAS. All rights reserved.