10-(4-((2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylphenyl)-N-((1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methyl)dec-9-ynamide | 1470060-76-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 10-(4-((2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylphenyl)-N-((1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methyl)dec-9-ynamide
• 英文别名: 10-[4-[2-(4-cyanoanilino)pyrimidin-4-yl]oxy-3,5-dimethylphenyl]-N-[[1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,4-dioxopyrimidin-5-yl]methyl]dec-9-ynamide
• CAS: 1470060-76-4
• 化学式: C₃₉H₄₃N₇O₇
• 分子量: 721.813
• InChiKey: IWOAXJWAQXDQSZ-GTXBZULCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  53
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  199
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  10-(4-((2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylphenyl)-N-((1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methyl)dec-9-ynamide 在 吡啶 、 2-氯-1,3,2-苯并二氧磷杂环己烷-4-酮 、 三丁基焦磷酸铵 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 ((2R,3S,5R)-5-(5-((10-(4-((2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylphenyl)dec-9-ynamido)methyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methyl 5’-hydrogen phosphonate 、 ((2R,3S,5R)-5-(5-((10-(4-((2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylphenyl)dec-9-ynamido)methyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methyl tetrahydrogen triphosphate
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Evaluation of Chimeric Inhibitors of HIV Reverse Transcriptase

  摘要：

  In a continuing study of potent bifunctional anti-HIV agents, we rationally designed a novel chimeric inhibitor utilizing thymidine (THY) and a TMC derivative (a diarylpyrimidine NNRTI) linked via a polymethylene linker (ALK). The nucleoside, 5'-hydrogen-phosphonate (H-phosphonate), and S'-triphosphate forms of this chimeric inhibitor (THY-ALK-TMC) were synthesized and the antiviral activity profiles were evaluated at the enzyme and cellular level. The nucleoside triphosphate (11) and the H-phosphonate (10) derivatives inhibited RT polymerization with an IC50 value of 6.0 and 4.3 nM, respectively. Additionally, chimeric nucleoside (9) and H-phosphonate (10) derivatives reduced HIV replication in a cell-based assay with low nanomolar antiviral potencies.

  DOI：

  10.1021/ml4002979
• 作为产物：
  描述：

  3,5-双-O-乙酰胸苷 在 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 四(三苯基膦)钯 、 sodium azide 、 偶氮二异丁腈 、 palladium 10% on activated carbon 、 水 、 氢气 、 potassium carbonate 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0~80.0 ℃ 、101.33 kPa 条件下， 反应 18.0h， 生成 10-(4-((2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylphenyl)-N-((1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methyl)dec-9-ynamide
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Evaluation of Chimeric Inhibitors of HIV Reverse Transcriptase

  摘要：

  In a continuing study of potent bifunctional anti-HIV agents, we rationally designed a novel chimeric inhibitor utilizing thymidine (THY) and a TMC derivative (a diarylpyrimidine NNRTI) linked via a polymethylene linker (ALK). The nucleoside, 5'-hydrogen-phosphonate (H-phosphonate), and S'-triphosphate forms of this chimeric inhibitor (THY-ALK-TMC) were synthesized and the antiviral activity profiles were evaluated at the enzyme and cellular level. The nucleoside triphosphate (11) and the H-phosphonate (10) derivatives inhibited RT polymerization with an IC50 value of 6.0 and 4.3 nM, respectively. Additionally, chimeric nucleoside (9) and H-phosphonate (10) derivatives reduced HIV replication in a cell-based assay with low nanomolar antiviral potencies.

  DOI：

  10.1021/ml4002979

文献信息

• Design, Synthesis, and Antiviral Evaluation of Chimeric Inhibitors of HIV Reverse Transcriptase
  作者：Pinar Iyidogan、Todd J. Sullivan、Mahendra D. Chordia、Kathleen M. Frey、Karen S. Anderson

  DOI：10.1021/ml4002979

  日期：2013.12.12

  In a continuing study of potent bifunctional anti-HIV agents, we rationally designed a novel chimeric inhibitor utilizing thymidine (THY) and a TMC derivative (a diarylpyrimidine NNRTI) linked via a polymethylene linker (ALK). The nucleoside, 5'-hydrogen-phosphonate (H-phosphonate), and S'-triphosphate forms of this chimeric inhibitor (THY-ALK-TMC) were synthesized and the antiviral activity profiles were evaluated at the enzyme and cellular level. The nucleoside triphosphate (11) and the H-phosphonate (10) derivatives inhibited RT polymerization with an IC50 value of 6.0 and 4.3 nM, respectively. Additionally, chimeric nucleoside (9) and H-phosphonate (10) derivatives reduced HIV replication in a cell-based assay with low nanomolar antiviral potencies.