(5E)-methyl 6-(3,4-dimethoxyphenyl)-2-hydroxy-4-oxo-2-hexa-2,5-dienoate | 1256291-02-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (5E)-methyl 6-(3,4-dimethoxyphenyl)-2-hydroxy-4-oxo-2-hexa-2,5-dienoate
• CAS: 1256291-02-7
• 化学式: C₁₅H₁₆O₆
• 分子量: 292.288
• InChiKey: FMSNJWHOOPLINE-ZACFJANWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  82.06
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (5E)-methyl 6-(3,4-dimethoxyphenyl)-2-hydroxy-4-oxo-2-hexa-2,5-dienoate 在 三溴化硼 、 水 作用下， 以 二氯甲烷 为溶剂， 以38%的产率得到(5E)-6-(3,4-dihydroxyphenyl)-2-hydroxy-4-oxo-hexa-2,5-dienoic acid
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Hybrid Dicaffeoyltartaric/Diketo Acid and Tetrazole-Substituted l-Chicoric Acid Analogue Inhibitors of Human Immunodeficiency Virus Type 1 Integrase

  摘要：

  Fourteen analogues of the anti-HIV-1 integrase (IN) inhibitor L-chicoric acid (L-CA) were prepared. Their IC50 values for 3'-end processing and strand transfer against recombinant HIV-1 IN were determined in vitro, and their cell toxicities and EC50 against HIV-1 were measured in cells (ex vivo). Compounds 1-6 are catechol/beta-diketoacid hybrids, the majority of which exhibit submicromolar potency against 3'-end processing and strand transfer, though only with modest antiviral activities. Compounds 7-10 are L-CA/p-fluorobenzylpyrroloyl hybrids, several of which were more potent against strand transfer than 3'-end processing, a phenomenon previously attributed to the beta-diketo acid pharmacophore. Compounds 11-14 are tetrazole bioisosteres of L-CA and its analogues, whose in vitro potencies were comparable to L-CA but with enhanced antiviral potency. The trihydroxyphenyl analogue 14 was 30-fold more potent than L-CA at relatively nontoxic concentrations. These data indicate that L-CA analogues are attractive candidates for development into clinically relevant inhibitors of HIV-1 IN.

  DOI：

  10.1021/jm1010594
• 作为产物：
  描述：

  草酸二甲酯 、 4-(3,4-二甲氧基苯基)-3-丁烯-2-酮 在 sodium methylate 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以98%的产率得到(5E)-methyl 6-(3,4-dimethoxyphenyl)-2-hydroxy-4-oxo-2-hexa-2,5-dienoate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Hybrid Dicaffeoyltartaric/Diketo Acid and Tetrazole-Substituted l-Chicoric Acid Analogue Inhibitors of Human Immunodeficiency Virus Type 1 Integrase

  摘要：

  Fourteen analogues of the anti-HIV-1 integrase (IN) inhibitor L-chicoric acid (L-CA) were prepared. Their IC50 values for 3'-end processing and strand transfer against recombinant HIV-1 IN were determined in vitro, and their cell toxicities and EC50 against HIV-1 were measured in cells (ex vivo). Compounds 1-6 are catechol/beta-diketoacid hybrids, the majority of which exhibit submicromolar potency against 3'-end processing and strand transfer, though only with modest antiviral activities. Compounds 7-10 are L-CA/p-fluorobenzylpyrroloyl hybrids, several of which were more potent against strand transfer than 3'-end processing, a phenomenon previously attributed to the beta-diketo acid pharmacophore. Compounds 11-14 are tetrazole bioisosteres of L-CA and its analogues, whose in vitro potencies were comparable to L-CA but with enhanced antiviral potency. The trihydroxyphenyl analogue 14 was 30-fold more potent than L-CA at relatively nontoxic concentrations. These data indicate that L-CA analogues are attractive candidates for development into clinically relevant inhibitors of HIV-1 IN.

  DOI：

  10.1021/jm1010594