DL-2,3-bis{[3-(3,4-dimethoxyphenyl)acryloyl]amino}propionic acid | 227098-04-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: DL-2,3-bis{[3-(3,4-dimethoxyphenyl)acryloyl]amino}propionic acid
• 英文别名: N,N-bis(3,4-dimethoxycinnamoyl)-2,3-diaminopropanoic acid；2,3-bis[[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino]propanoic acid
• CAS: 227098-04-6
• 化学式: C₂₅H₂₈N₂O₈
• 分子量: 484.506
• InChiKey: BRBMUUZATYIVGN-MKICQXMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  特戊酸氯甲酯 、 DL-2,3-bis{[3-(3,4-dimethoxyphenyl)acryloyl]amino}propionic acid 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of chicoric acid analogs as inhibitors of HIV-1 integrase

  摘要：

  A series of analogs of the potent HIV-1 integrase (HIV IN) inhibitor chicoric acid (CA) was designed with the intention of ameliorating some of the parent natural product's undesirable properties, in particular its toxicity, instability, and poor membrane permeability. More than 70 analogs were synthesized and assayed for three types of activity: (1) the ability to inhibit 3'-end processing and strand transfer reactions using recombinant HIV IN in vitro, (2) toxicity against the CD4+ lymphoblastoid cell line, MT2, and (3) anti-HIV activity against HIVLAI. CA analogs lacking one of the carboxyl groups of CA and with 3,4,5-trihydroxycinnamoyl sidechains in place of the caffeoyl group of CA exhibited the most potent inhibition of HIV replication and end-processing activity. Galloyl-substituted derivatives also displayed very potent in vitro and in vivo activities, in most cases exceeding the inhibitory effects of CA itself. Conversely, analogous monocarboxy caffeoyl analogs exhibited only modest inhibition, while the corresponding 3,4-dihydroxybenzoyl-substituted compounds were devoid of activity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.030
• 作为产物：
  描述：

  3,4-二甲氧基肉酸酸 在 N-甲基吗啉 、 吡啶 、 1-羟基苯并三唑一水物 、 lithium iodide 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 DL-2,3-bis{[3-(3,4-dimethoxyphenyl)acryloyl]amino}propionic acid
  参考文献：
  名称：

  Chicoric Acid Analogues as HIV-1 Integrase Inhibitors

  摘要：

  The present study was undertaken to examine structural features of L-chicoric acid (3) which are important for potency against purified HIV-1 integrase and for reported cytoprotective effects in cell-based systems. Through a progressive series of analogues, it was shown that enantiomeric D-chicoric acid (4) retains inhibitory potency against purified integrase equal to its L-counterpart and further that removal of either one or both carboxylic functionalities results in essentially no loss of inhibitory potency. Additionally, while two caffeoyl moieties are required, attachment of caffeoyl groups to the central linking structure can be achieved via amide or mixed amide/ester linkages. More remarkable is the finding that blockage of the catechol functionality through conversion to tetraacetate esters results in almost no loss of potency, contingent on the presence of at least one carboxyl group on the central linker. Taken as a whole, the work has resulted in the identification of new integrase inhibitors which may be regarded as bis-caffeoyl derivatives of glycidic acid and amino acids such as serine and beta-aminoalanine. The present study also examined the reported ability of chicoric acid to exert cytoprotective effects in HIV-infected cells. It was demonstrated in target and cell-based assays that the chicoric acids do not significantly inhibit other targets associated with HIV-1 replication, including reverse transcription, protease function, NCp7 zinc finger function, or replication of virus from latently infected cells. In CEM cells, for both the parent chicoric acid and selected analogues, antiviral activity was observable under specific assay conditions and with high dependence on the multiplicity of viral infection. However, against HIV-1- and HIV-2-infected MT-4 cells, the chicoric acids and their tetraacetylated esters exhibited antiviral activity (50% effective concentration (EC(50)) ranging from 1.7 to 20 mu M and 50% inhibitory concentration (IC(50)) ranging from 40 to 60 mu M).

  DOI：

  10.1021/jm980531m

文献信息

• Design, synthesis, and biological evaluation of chicoric acid analogs as inhibitors of HIV-1 integrase
  作者：Trevor T. Charvat、Deborah J. Lee、W. Edward Robinson、A. Richard Chamberlin

  DOI：10.1016/j.bmc.2006.02.030

  日期：2006.7

  A series of analogs of the potent HIV-1 integrase (HIV IN) inhibitor chicoric acid (CA) was designed with the intention of ameliorating some of the parent natural product's undesirable properties, in particular its toxicity, instability, and poor membrane permeability. More than 70 analogs were synthesized and assayed for three types of activity: (1) the ability to inhibit 3'-end processing and strand transfer reactions using recombinant HIV IN in vitro, (2) toxicity against the CD4+ lymphoblastoid cell line, MT2, and (3) anti-HIV activity against HIVLAI. CA analogs lacking one of the carboxyl groups of CA and with 3,4,5-trihydroxycinnamoyl sidechains in place of the caffeoyl group of CA exhibited the most potent inhibition of HIV replication and end-processing activity. Galloyl-substituted derivatives also displayed very potent in vitro and in vivo activities, in most cases exceeding the inhibitory effects of CA itself. Conversely, analogous monocarboxy caffeoyl analogs exhibited only modest inhibition, while the corresponding 3,4-dihydroxybenzoyl-substituted compounds were devoid of activity. (c) 2006 Elsevier Ltd. All rights reserved.
• Chicoric Acid Analogues as HIV-1 Integrase Inhibitors
  作者：Zhaiwei Lin、Nouri Neamati、He Zhao、Yoshimitsu Kiryu、Jim A. Turpin、Claudia Aberham、Klaus Strebel、Kurt Kohn、Myriam Witvrouw、Christophe Pannecouque、Zeger Debyser、Erik De Clercq、William G. Rice、Yves Pommier、Terrence R. Burke

  DOI：10.1021/jm980531m

  日期：1999.4.22

  The present study was undertaken to examine structural features of L-chicoric acid (3) which are important for potency against purified HIV-1 integrase and for reported cytoprotective effects in cell-based systems. Through a progressive series of analogues, it was shown that enantiomeric D-chicoric acid (4) retains inhibitory potency against purified integrase equal to its L-counterpart and further that removal of either one or both carboxylic functionalities results in essentially no loss of inhibitory potency. Additionally, while two caffeoyl moieties are required, attachment of caffeoyl groups to the central linking structure can be achieved via amide or mixed amide/ester linkages. More remarkable is the finding that blockage of the catechol functionality through conversion to tetraacetate esters results in almost no loss of potency, contingent on the presence of at least one carboxyl group on the central linker. Taken as a whole, the work has resulted in the identification of new integrase inhibitors which may be regarded as bis-caffeoyl derivatives of glycidic acid and amino acids such as serine and beta-aminoalanine. The present study also examined the reported ability of chicoric acid to exert cytoprotective effects in HIV-infected cells. It was demonstrated in target and cell-based assays that the chicoric acids do not significantly inhibit other targets associated with HIV-1 replication, including reverse transcription, protease function, NCp7 zinc finger function, or replication of virus from latently infected cells. In CEM cells, for both the parent chicoric acid and selected analogues, antiviral activity was observable under specific assay conditions and with high dependence on the multiplicity of viral infection. However, against HIV-1- and HIV-2-infected MT-4 cells, the chicoric acids and their tetraacetylated esters exhibited antiviral activity (50% effective concentration (EC(50)) ranging from 1.7 to 20 mu M and 50% inhibitory concentration (IC(50)) ranging from 40 to 60 mu M).