tetraacetyl-L-chicoric acid

• 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: tetraacetyl-L-chicoric acid
• 英文别名: (2R,3R)-2,3-bis[3-(3,4-diacetyloxyphenyl)prop-2-enoyloxy]butanedioic acid
• 化学式: C₃₀H₂₆O₁₆
• 分子量: 642.527
• InChiKey: RMUUAKSNUFVKKT-VSGBNLITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  46
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  232
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  bisdiphenylmethyl tetraacetyl-L-chicorate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以98%的产率得到tetraacetyl-L-chicoric acid
  参考文献：
  名称：

  Dicaffeoyltartaric Acid Analogues Inhibit Human Immunodeficiency Virus Type 1 (HIV-1) Integrase and HIV-1 Replication at Nontoxic Concentrations

  摘要：

  The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of L-chicoric acid, a potent inhibitor of HIV integrase were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less than 10 muM were identified. Six demonstrated greater than 10-fold selectivity for HIV replication over cellular toxicity. Ten analogues inhibited HIV replication at nontoxic concentrations. Alteration of the linkages between the two bis-catechol rings, including the use of amides, mixed amide esters, cholate, and alkyl bridges, was explored. Amides were as active as esters but were more toxic in tissue culture. Alkyl and cholate bridges were significantly less potent against HIV-1 integrase in vitro and were inactive against HIV-1 replication. Two amino acid derivates and one digalloylderivative of L-chicoric acid (L-CA) showed improved selectivity over L-CA against integration in cell culture. These data suggest that in addition to the bis-catechols and free carboxylic acid groups reported previously, polar linkages are important constituents for optimal activity against HIV-1 integrase and that new derivatives can be developed with increased specificity for integration over HIV entry in vivo.

  DOI：

  10.1021/jm010359d

文献信息

• Dicaffeoyltartaric Acid Analogues Inhibit Human Immunodeficiency Virus Type 1 (HIV-1) Integrase and HIV-1 Replication at Nontoxic Concentrations
  作者：Ryan A. Reinke、Peter J. King、Joseph G. Victoria、Brenda R. McDougall、Guoxiang Ma、Yingqun Mao、Manfred G. Reinecke、W. Edward Robinson

  DOI：10.1021/jm010359d

  日期：2002.8.1

  The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of L-chicoric acid, a potent inhibitor of HIV integrase were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less than 10 muM were identified. Six demonstrated greater than 10-fold selectivity for HIV replication over cellular toxicity. Ten analogues inhibited HIV replication at nontoxic concentrations. Alteration of the linkages between the two bis-catechol rings, including the use of amides, mixed amide esters, cholate, and alkyl bridges, was explored. Amides were as active as esters but were more toxic in tissue culture. Alkyl and cholate bridges were significantly less potent against HIV-1 integrase in vitro and were inactive against HIV-1 replication. Two amino acid derivates and one digalloylderivative of L-chicoric acid (L-CA) showed improved selectivity over L-CA against integration in cell culture. These data suggest that in addition to the bis-catechols and free carboxylic acid groups reported previously, polar linkages are important constituents for optimal activity against HIV-1 integrase and that new derivatives can be developed with increased specificity for integration over HIV entry in vivo.