3,5-bis(3,4-dimethoxycinnamoylamino)acetophenone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,5-bis(3,4-dimethoxycinnamoylamino)acetophenone
• 英文别名: (E)-N-[3-acetyl-5-[[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino]phenyl]-3-(3,4-dimethoxyphenyl)prop-2-enamide
• 化学式: C₃₀H₃₀N₂O₇
• 分子量: 530.577
• InChiKey: QZYUXEVPRROLET-QHKWOANTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  草酸二甲酯 、 3,5-bis(3,4-dimethoxycinnamoylamino)acetophenone 在 sodium methylate 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 5.0h， 以95%的产率得到methyl 4-(3,5-bis(3,4-dimethoxycinnamoylamino)phenyl)-2-hydroxy-4-oxo-2-butenoate
  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：

  3,5-二氨基苯乙酮 、 3,4-二甲氧基肉桂酰氯 在 吡啶 、 水 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 4.0h， 以89%的产率得到3,5-bis(3,4-dimethoxycinnamoylamino)acetophenone
  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

文献信息

• Design, Synthesis, and Biological Evaluation of Novel Hybrid Dicaffeoyltartaric/Diketo Acid and Tetrazole-Substituted <scp>l</scp>-Chicoric Acid Analogue Inhibitors of Human Immunodeficiency Virus Type 1 Integrase
  作者：David C. Crosby、Xiangyang Lei、Charles G. Gibbs、Brenda R. McDougall、W. Edward Robinson、Manfred G. Reinecke

  DOI：10.1021/jm1010594

  日期：2010.11.25

  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.