3-(3,4-dihydroxyphenyl)propanoic acid pentafluorophenyl ester | 169232-24-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 3-(3,4-dihydroxyphenyl)propanoic acid pentafluorophenyl ester
• 英文别名: pentafluorophenyl 3-(3,4-dihydroxyphenyl)propanoate；(2,3,4,5,6-Pentafluorophenyl) 3-(3,4-dihydroxyphenyl)propanoate
• CAS: 169232-24-0
• 化学式: C₁₅H₉F₅O₄
• 分子量: 348.226
• InChiKey: GHTACWUMUAFWCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  盐酸多巴胺 、 3-(3,4-dihydroxyphenyl)propanoic acid pentafluorophenyl ester 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以100%的产率得到N-(3,4-dihydroxyhydrocinnamoyl)dopamine
  参考文献：
  名称：

  Hydroxylated Aromatic Inhibitors of HIV-1 Integrase

  摘要：

  Efficient replication of HIV-1 requires integration of a DNA copy of the viral genome into a chromosome of the host cell. Integration is catalyzed by the viral integrase, and we have previously reported that phenolic moieties in compounds such as flavones, caffeic acid phenethyl ester (CAFE, 2), and curcumin confer inhibitory activity against HIV-1 integrase. We now extend these findings by performing a comprehensive structure-activity relationship using CAPE analogues. Approximately 30 compounds have been prepared as HIV integrase inhibitors based on the structural lead provided by CAPE, which has previously been shown to exhibit an IC50 value of 7 mu M in our integration assay. These analogues were designed to examine specific features of the parent CAFE structure which may be important for activity. Among the features examined for their effects on inhibitory potency were ring substitution, side chain length and composition, and phenyl ring conformational orientation. In an assay which measured the combined effect of two sequential steps, dinucleotide cleavage and strand transfer, several analogues have IC50 values for 3'-processing and strand transfer lower than those of CAFE. Inhibition of strand transfer was assayed using both blunt-ended and ''precleaved'' DNA substrates. Disintegration using an integrase mutant lacking the N-terminal zinc finger and C-terminal DNA-binding domains was also inhibited by these analogues, suggesting that the binding site for these compounds resides in the central catalytic core. Several CAFE analogues were also tested for selective activity against transformed cells. Taken together, these results suggest that the development of novel antiviral agents for the treatment of acquired immune deficiency syndrome can be based upon inhibition of HIV-1 integrase.

  DOI：

  10.1021/jm00021a006
• 作为产物：
  描述：

  TRANS-咖啡酸 在 palladium on activated charcoal 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-(3,4-dihydroxyphenyl)propanoic acid pentafluorophenyl ester
  参考文献：
  名称：

  Hydroxylated Aromatic Inhibitors of HIV-1 Integrase

  摘要：

  Efficient replication of HIV-1 requires integration of a DNA copy of the viral genome into a chromosome of the host cell. Integration is catalyzed by the viral integrase, and we have previously reported that phenolic moieties in compounds such as flavones, caffeic acid phenethyl ester (CAFE, 2), and curcumin confer inhibitory activity against HIV-1 integrase. We now extend these findings by performing a comprehensive structure-activity relationship using CAPE analogues. Approximately 30 compounds have been prepared as HIV integrase inhibitors based on the structural lead provided by CAPE, which has previously been shown to exhibit an IC50 value of 7 mu M in our integration assay. These analogues were designed to examine specific features of the parent CAFE structure which may be important for activity. Among the features examined for their effects on inhibitory potency were ring substitution, side chain length and composition, and phenyl ring conformational orientation. In an assay which measured the combined effect of two sequential steps, dinucleotide cleavage and strand transfer, several analogues have IC50 values for 3'-processing and strand transfer lower than those of CAFE. Inhibition of strand transfer was assayed using both blunt-ended and ''precleaved'' DNA substrates. Disintegration using an integrase mutant lacking the N-terminal zinc finger and C-terminal DNA-binding domains was also inhibited by these analogues, suggesting that the binding site for these compounds resides in the central catalytic core. Several CAFE analogues were also tested for selective activity against transformed cells. Taken together, these results suggest that the development of novel antiviral agents for the treatment of acquired immune deficiency syndrome can be based upon inhibition of HIV-1 integrase.

  DOI：

  10.1021/jm00021a006

文献信息

• Arylamide Inhibitors of HIV-1 Integrase
  作者：He Zhao、Nouri Neamati、Abhijit Mazumder、Sanjay Sunder、Yves Pommier、Terrence R. Burke

  DOI：10.1021/jm960449w

  日期：1997.4.1

  Based on data derived from a large number of HIV-1 integrase inhibitors, similar structural features can be observed, which consist of two aryl units separated by a central linker. For many inhibitors fitting this pattern, at least one aryl ring also requires ortho bis-hydroxylation for significant inhibitory potency. The ability of such catechol species to undergo in situ oxidation to reactive quinones

  根据来自大量HIV-1整合酶抑制剂的数据，可以观察到相似的结构特征，该特征由两个被中央连接子分隔的芳基单元组成。对于许多符合这种模式的抑制剂，至少一个芳基环也需要邻双羟基化以显着抑制作用。这类邻苯二酚物质原位氧化成反应性醌的能力对其实用性提出了一种潜在的限制。为了解决这个问题，制备了一系列不含邻双羟基的抑制剂。这些类似物均未显示出明显的抑制作用。因此，采取了另一种方法，其目的是增加效力而不是消除儿茶酚的亚结构。在后面的研究中，萘核被用作芳基成分，因为先前的报告已经表明，相对于基于单环苯基的系统，稠合的双环可能具有更高的亲和力。在单体单元的初步工作中，发现6,7-二羟基-2-萘甲酸（17）（IC50 = 4.7 microM）的效力比其5,6-二羟基异构体19（IC50 = 62.4微米）。特别值得注意的是，游离酸17和其甲酯21的效价之间存在巨大差异（IC50> 200 microM）。由
• Activation of hydrocinnamic acids with pentafluorophenol versus pentafluorothiophenol: Reactivity towards hexylamine
  作者：Fernanda M.F. Roleira、Fernanda Borges、Lourdes C.R. Andrade、José A. Paixão、Maria J.M. Almeida、Rui A. Carvalho、Elisiário J. Tavares da Silva

  DOI：10.1016/j.jfluchem.2008.09.013

  日期：2009.2

  In this work we describe and compare the synthesis of four new hexylamides of hydrocinnamic acids, namely hexylamide of hydrocinnamic, 3,4-dimethoxyhydrocinnamic, 4-hydroxy-3-methoxyhydrocinnamic and 3,4-dihydroxyhydrocinnamic acids via pentafluorophenyl esters (PFPEs) versus pentafluorophenyl thioesters (PFPTs) intermediates. It was found that the PRE are the best intermediates for this kind of synthesis giving reactions with less by products, easier work-up, higher overall yields and with the best reactivity towards hexylamine. The X-ray structures of two PRE are also reported. (C) 2008 Elsevier B.V. All rights reserved.
• A METHOD FOR THE TREATMENT OF HYPERPROLIFERATIVE EPITHELIAL SKIN DISEASES BY TOPICAL APPLICATION OF HYDROXYLATED AROMATIC PROTEIN CROSS-LINKING COMPOUNDS
  申请人：THE UNITED STATES GOVERNMENT as represented by THE DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：EP0809493A1

  公开（公告）日：1997-12-03
• US5610185A
  申请人：——

  公开号：US5610185A

  公开（公告）日：1997-03-11
• [EN] A METHOD FOR THE TREATMENT OF HYPERPROLIFERATIVE EPITHELIAL SKIN DISEASES BY TOPICAL APPLICATION OF HYDROXYLATED AROMATIC PROTEIN CROSS-LINKING COMPOUNDS<br/>[FR] PROCEDE POUR TRAITER LES LESIONS EPITHELIALES HYPERPROLIFERATIVES DE LA PEAU PAR APPLICATION TOPIQUE DE COMPOSES DE RETICULATION DE PROTEINES AROMATIQUES HYDROXYLES
  申请人：THE GOVERNMENT OF THE UNITED STATES OF AMERICA, represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：WO1996025159A1

  公开（公告）日：1996-08-22

  (EN) The present invention relates to a method of treating hyperproliferative epithelial lesions by topical administration. The method prevents growth and actively cross-links these aberrant cells, thereby killing the cells. The present invention is useful in control and prevention of hyperproliferative epithelial disorders, such as HPV-infected cell lesions, actinic keratosis, melanomas, and malignant and pre-malignant carcinomas.(FR) Cette invention se rapporte à un procédé pour traiter les lésions épithéliales hyperprolifératives de la peau par administration topique. Ce procédé empêche la croissance et entraîne la réticulation active de ces cellules aberrantes, afin de les détruire. Cette invention permet de combattre et prévenir les troubles épithéliaux hyperprolifératifs, telles que les lésions cellulaires infectées par HPV, la kératose actinique, les mélanomes et les carcinomes malins et prémalins.