methyl 4-[3-(benzyloxy)phenyl]-2,4-dioxobutanoate | 608537-02-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 4-[3-(benzyloxy)phenyl]-2,4-dioxobutanoate
• 英文别名: Methyl 2,4-dioxo-4-(3-phenylmethoxyphenyl)butanoate
• CAS: 608537-02-6
• 化学式: C₁₈H₁₆O₅
• 分子量: 312.322
• InChiKey: NHVBENWXEDDAQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-[3-(benzyloxy)phenyl]-2,4-dioxobutanoate 在 溶剂黄146 、 肼 作用下， 反应 1.0h， 生成 methyl 5-[3-(benzyloxy)phenyl]-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors

  摘要：

  Three new types of aryl diketo acid (ADK) isosteres were designed by conversion of the biologically labile 1,3-diketo unit into heteroaromatic motif such as isoxazole, isothiazole, or 1H-pyrazole to improve the physicochemical property of ADK-based HIV-1 integrase (IN) inhibitors. The synthesis of the heteroaromatic carboxylic acids was established by employing phenyl beta-diketoester or benzaldehyde as the starting material and 1,3-dipolar cycloaddition as the key reaction. Of the compounds tested, the 3-benzyloxyphenyl-substituted isoxazole carboxylic acid displayed the best IN inhibitory and antiviral activities, with N-hydroxylamidation enhancing the in vitro and in vivo potency. These findings are important for further optimization of ADK-based IN inhibitors. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.047
• 作为产物：
  描述：

  草酸二甲酯 、 3-苄氧基苯乙酮 在 sodium t-butanolate 作用下， 以 四氢呋喃 为溶剂， 生成 methyl 4-[3-(benzyloxy)phenyl]-2,4-dioxobutanoate
  参考文献：
  名称：

  Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors

  摘要：

  Three new types of aryl diketo acid (ADK) isosteres were designed by conversion of the biologically labile 1,3-diketo unit into heteroaromatic motif such as isoxazole, isothiazole, or 1H-pyrazole to improve the physicochemical property of ADK-based HIV-1 integrase (IN) inhibitors. The synthesis of the heteroaromatic carboxylic acids was established by employing phenyl beta-diketoester or benzaldehyde as the starting material and 1,3-dipolar cycloaddition as the key reaction. Of the compounds tested, the 3-benzyloxyphenyl-substituted isoxazole carboxylic acid displayed the best IN inhibitory and antiviral activities, with N-hydroxylamidation enhancing the in vitro and in vivo potency. These findings are important for further optimization of ADK-based IN inhibitors. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.047

文献信息

• Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors
  作者：Li-Fan Zeng、Hu-Shan Zhang、Yun-Hua Wang、Tino Sanchez、Yong-Tang Zheng、Nouri Neamati、Ya-Qiu Long

  DOI：10.1016/j.bmcl.2008.07.047

  日期：2008.8

  Three new types of aryl diketo acid (ADK) isosteres were designed by conversion of the biologically labile 1,3-diketo unit into heteroaromatic motif such as isoxazole, isothiazole, or 1H-pyrazole to improve the physicochemical property of ADK-based HIV-1 integrase (IN) inhibitors. The synthesis of the heteroaromatic carboxylic acids was established by employing phenyl beta-diketoester or benzaldehyde as the starting material and 1,3-dipolar cycloaddition as the key reaction. Of the compounds tested, the 3-benzyloxyphenyl-substituted isoxazole carboxylic acid displayed the best IN inhibitory and antiviral activities, with N-hydroxylamidation enhancing the in vitro and in vivo potency. These findings are important for further optimization of ADK-based IN inhibitors. (c) 2008 Elsevier Ltd. All rights reserved.