methyl 5-(benzoyloxy)-2-isopropyl-1-methyl-6-oxo-1,6-dihydropyrimidin-4-carboxylate | 1350906-15-8

• 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: methyl 5-(benzoyloxy)-2-isopropyl-1-methyl-6-oxo-1,6-dihydropyrimidin-4-carboxylate
• 英文别名: methyl 5-benzyloxy-2-isopropyl-1-methyl-6-oxo-1,6-dihydroxypyrimidine-4-carboxylate；Methyl 5-benzoyloxy-1-methyl-6-oxo-2-propan-2-ylpyrimidine-4-carboxylate
• CAS: 1350906-15-8
• 化学式: C₁₇H₁₈N₂O₅
• 分子量: 330.34
• InChiKey: SYKDPFHPHPKJSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  85.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 5-(benzoyloxy)-2-isopropyl-1-methyl-6-oxo-1,6-dihydropyrimidin-4-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 7.0h， 生成 Magnesium 4-[(4-fluorophenyl)methylcarbamoyl]-2-isopropyl-1-methyl-6-oxo-pyrimidin-5-olate
  参考文献：
  名称：

  Investigating the Role of Metal Chelation in HIV-1 Integrase Strand Transfer Inhibitors

  摘要：

  HIV-1 integrase (IN) has been validated as an attractive target for the treatment of HIV/AIDS. Several studies have confirmed that the metal binding function is a crucial feature in many of the reported IN inhibitors. To provide new insights on the metal chelating mechanism of IN inhibitors, we prepared a series of metal complexes of two ligands (HL1 and HL2), designed as representative models of the clinically used compounds raltegravir and elvitegravir. Potentiometric measurements were conducted for HL2 in the presence of Mg(II), Mn(II), Co(II), and Zn(II) in order to delineate a metal speciation model. We also determined the X-ray structures of both of the ligands and of three representative metal complexes. Our results support the hypothesis that several selective strand transfer inhibitors preferentially chelate one cation in solution and that the metal complexes can interact with the active site of the enzyme.

  DOI：

  10.1021/jm200851g
• 作为产物：
  描述：

  苯甲酸酐 在 吡啶 、 caesium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 72.33h， 生成 methyl 5-(benzoyloxy)-2-isopropyl-1-methyl-6-oxo-1,6-dihydropyrimidin-4-carboxylate
  参考文献：
  名称：

  用于人类免疫缺陷病毒 1 整合酶捕获的基于 Raltegravir 的光亲和标记探针的开发

  摘要：

  光亲和标记 (PAL) 是分子识别领域即将到来的强大工具之一。它包括动态参数的确定，例如目标蛋白的识别和定位以及药物结合位点。在这项研究中，按照 FDA 批准的药物 Raltegravir 的结构，设计并合成了一种用于全长人类免疫缺陷病毒 1 整合酶 (HIV-1 IN) 捕获的光亲和标记探针。发现该光探针与其母体分子相比保留了 HIV IN 抑制潜力，并证明了标记 HIV-1 IN 蛋白的能力。在蛋白质消化与质量和分子建模分析相结合后，然后确定催化位点附近的假定光探针/抑制剂结合位点。

  DOI：

  10.1021/acsmedchemlett.0c00009

文献信息

• Investigating the Role of Metal Chelation in HIV-1 Integrase Strand Transfer Inhibitors
  作者：Alessia Bacchi、Mauro Carcelli、Carlotta Compari、Emilia Fisicaro、Nicolino Pala、Gabriele Rispoli、Dominga Rogolino、Tino W. Sanchez、Mario Sechi、Valentina Sinisi、Nouri Neamati

  DOI：10.1021/jm200851g

  日期：2011.12.22

  HIV-1 integrase (IN) has been validated as an attractive target for the treatment of HIV/AIDS. Several studies have confirmed that the metal binding function is a crucial feature in many of the reported IN inhibitors. To provide new insights on the metal chelating mechanism of IN inhibitors, we prepared a series of metal complexes of two ligands (HL1 and HL2), designed as representative models of the clinically used compounds raltegravir and elvitegravir. Potentiometric measurements were conducted for HL2 in the presence of Mg(II), Mn(II), Co(II), and Zn(II) in order to delineate a metal speciation model. We also determined the X-ray structures of both of the ligands and of three representative metal complexes. Our results support the hypothesis that several selective strand transfer inhibitors preferentially chelate one cation in solution and that the metal complexes can interact with the active site of the enzyme.
• Development of a Raltegravir-based Photoaffinity-Labeled Probe for Human Immunodeficiency Virus-1 Integrase Capture
  作者：Nicolino Pala、Francesca Esposito、Enzo Tramontano、Pankaj Kumar Singh、Vanna Sanna、Mauro Carcelli、Lisa D. Haigh、Sandro Satta、Mario Sechi

  DOI：10.1021/acsmedchemlett.0c00009

  日期：2020.10.8

  Photoaffinity labeling (PAL) is one of the upcoming and powerful tools in the field of molecular recognition. It includes the determination of dynamic parameters, such as the identification and localization of the target protein and the site of drug binding. In this study, a photoaffinity-labeled probe for full-length human immunodeficiency virus-1 integrase (HIV-1 IN) capture was designed and synthesized

  光亲和标记 (PAL) 是分子识别领域即将到来的强大工具之一。它包括动态参数的确定，例如目标蛋白的识别和定位以及药物结合位点。在这项研究中，按照 FDA 批准的药物 Raltegravir 的结构，设计并合成了一种用于全长人类免疫缺陷病毒 1 整合酶 (HIV-1 IN) 捕获的光亲和标记探针。发现该光探针与其母体分子相比保留了 HIV IN 抑制潜力，并证明了标记 HIV-1 IN 蛋白的能力。在蛋白质消化与质量和分子建模分析相结合后，然后确定催化位点附近的假定光探针/抑制剂结合位点。