methyl (2S)-2-[[(E)-3-(3,4-diacetoxyphenyl)prop-2-enoyl]amino]-3-[(E)-3-(3,4-diacetoxyphenyl)prop-2-enoyl]oxy-propanoate

• 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: methyl (2S)-2-[[(E)-3-(3,4-diacetoxyphenyl)prop-2-enoyl]amino]-3-[(E)-3-(3,4-diacetoxyphenyl)prop-2-enoyl]oxy-propanoate
• 英文别名: methyl (2S)-2-[[(E)-3-(3,4-diacetyloxyphenyl)prop-2-enoyl]amino]-3-[(E)-3-(3,4-diacetyloxyphenyl)prop-2-enoyl]oxypropanoate
• 化学式: C₃₀H₂₉NO₁₃
• 分子量: 611.559
• InChiKey: DYNBPLCSQQIQFD-GNLSCFOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  44
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  187
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  (E)-3,4-di-O-acetylcaffeoyl chloride 、 L-丝氨酸甲酯盐酸盐 在 吡啶 作用下， 以 甲苯 为溶剂， 以76%的产率得到methyl (2S)-2-[[(E)-3-(3,4-diacetoxyphenyl)prop-2-enoyl]amino]-3-[(E)-3-(3,4-diacetoxyphenyl)prop-2-enoyl]oxy-propanoate
  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

• [EN] ACETYLATED AND RELATED ANALOGUES OF CHICORIC ACID AS HIV INTEGRASE INHIBITORS<br/>[FR] ANALOGUES ACETYLES ET CORRESPONDANTS D'ACIDE CHICORIQUE EN TANT QU'INHIBITEURS DE L'INTEGRASE DU VIH
  申请人：US HEALTH

  公开号：WO2000063152A1

  公开（公告）日：2000-10-26

  Chicoric acid analogues and derivatives have activity against HIV-1 integrase. The structural features that are required for this activity are elucidated by assaying these analogues and derivatives against HIV-1 integrase. Furthermore, methods of synthesis of the enantiomers of chicoric acid itself, as well as its analogues and derivatives, are disclosed. Additionally, methods of use of chicoric acid analogues and derivatives to inhibit HIV-1 integrase are disclosed, as are compositions comprising chicoric acid analogues and derivatives.

  Chicoric酸类似物和衍生物具有抗HIV-1整合酶的活性。通过对这些类似物和衍生物对HIV-1整合酶的测定，阐明了实现这种活性所需的结构特征。此外，还公开了合成Chicoric酸本身及其类似物和衍生物的对映体的方法。此外，还公开了使用Chicoric酸类似物和衍生物抑制HIV-1整合酶的方法，以及包含Chicoric酸类似物和衍生物的组合物。
• 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).