2-(4-((苯氧基硫代甲基)氨基)苯基)甲烷-1-醇 | 302576-99-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(4-((苯氧基硫代甲基)氨基)苯基)甲烷-1-醇
• 英文名称: 2-(4-((phenoxythioxomethyl)amino)phenyl)methan-1-ol
• 英文别名: 2-(4-((phenoxythioxomethyl)amino)phenyl)ethan-1-ol；O-phenyl N-[4-(2-hydroxyethyl)phenyl]carbamothioate
• CAS: 302576-99-4
• 化学式: C₁₅H₁₅NO₂S
• 分子量: 273.356
• InChiKey: KSLCMNYJMUEKMV-UHFFFAOYSA-N

物化性质

• 沸点：
  412.2±47.0 °C(Predicted)
• 密度：
  1.285±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 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：
  73.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-((苯氧基硫代甲基)氨基)苯基)甲烷-1-醇 在 吡啶 、 三氯硅烷 、 三乙胺 作用下， 以 甲苯 、 苯 为溶剂， 反应 1.0h， 生成 2-(4-isothiocyanatophenyl)ethyl (E)-3-(3,4-dimethoxyphenyl)prop-2-enoate
  参考文献：
  名称：

  Arylisothiocyanate-Containing esters of caffeic acid designed as affinity ligands for HIV-1 integrase

  摘要：

  Integrase is an enzyme found in human immunodeficiency virus, which is required for the viral life cycle, yet has no human cellular homologue. For this reason, HIV integrase (IN) has become an important target for the development of new AIDS therapeutics. Irreversible affinity ligands have proven to be valuable tools for studying a number of enzyme and protein systems. yet to date there have been no reports of such affinity ligands for the study of IN. As an initial approach toward irreversible ligand design directed against IN, we appended isothiocyanate functionality onto caffeic acid phenethyl ester (CAPE), a known HIV integrase inhibitor. The choice of isothiocyanate as the reactive functionality, was based on its demonstrated utility in the preparation of affinity ligands directed against a number of other protein targets. Several isomeric CAFE isothiocyanates were prepared to explore the enzyme topography for reactive nitrogen and sulfur nucleophiles vicinal to the enzyme-bound CAFE. The preparation of these CAFE isothiocyanates. required development of new synthetic methodology which employed phenyl thiocarbamates as latent isothiocyanates which could be unmasked near the end of the synthetic sequence. When it was observed that beta -mercaptoethanol (beta -ME), which is required to maintain the catalytic activity of soluble IN (a F185KC280S mutant), reacted with CAFE isothiocyanate functionality to form the corresponding hydroxyethylthiocarbamate, a variety of mutant IN were examined which did not require the presence of beta -ME for catalytic activity. Although in these latter enzymes, CAFE isothiocyanate functionality was presumed to be present and available for acylation by IN nucleophiles, they were equally effective against Cys to Ser mutants. One conclusion of these studies. is that upon binding of CAFE to the integrase, nitrogen or sulfur nucleophiles may not be properly situated in the vicinity of the phenethyl aryl ring to allow reaction with and covalent modification of reactive functionality, such as isothiocyanate groups. The fact that introduction of the isothiocyanate group onto various positions of the phenethyl ring or replacement of the phenyl ring with naphthyl rings, failed to significantly affect inhibitory potency, indicates a degree of insensitivity of this region of the molecule toward structural modification. These findings may be useful in future studies concerned with the development and use of HIV-1 integrase affinity ligands. (C) 2001 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(01)00075-x
• 作为产物：
  描述：

  硫代氯甲酸苯酯 、 4-氨基苯乙醇 以 四氢呋喃 为溶剂， 反应 0.5h， 以77%的产率得到2-(4-((苯氧基硫代甲基)氨基)苯基)甲烷-1-醇
  参考文献：
  名称：

  Arylisothiocyanate-Containing esters of caffeic acid designed as affinity ligands for HIV-1 integrase

  摘要：

  Integrase is an enzyme found in human immunodeficiency virus, which is required for the viral life cycle, yet has no human cellular homologue. For this reason, HIV integrase (IN) has become an important target for the development of new AIDS therapeutics. Irreversible affinity ligands have proven to be valuable tools for studying a number of enzyme and protein systems. yet to date there have been no reports of such affinity ligands for the study of IN. As an initial approach toward irreversible ligand design directed against IN, we appended isothiocyanate functionality onto caffeic acid phenethyl ester (CAPE), a known HIV integrase inhibitor. The choice of isothiocyanate as the reactive functionality, was based on its demonstrated utility in the preparation of affinity ligands directed against a number of other protein targets. Several isomeric CAFE isothiocyanates were prepared to explore the enzyme topography for reactive nitrogen and sulfur nucleophiles vicinal to the enzyme-bound CAFE. The preparation of these CAFE isothiocyanates. required development of new synthetic methodology which employed phenyl thiocarbamates as latent isothiocyanates which could be unmasked near the end of the synthetic sequence. When it was observed that beta -mercaptoethanol (beta -ME), which is required to maintain the catalytic activity of soluble IN (a F185KC280S mutant), reacted with CAFE isothiocyanate functionality to form the corresponding hydroxyethylthiocarbamate, a variety of mutant IN were examined which did not require the presence of beta -ME for catalytic activity. Although in these latter enzymes, CAFE isothiocyanate functionality was presumed to be present and available for acylation by IN nucleophiles, they were equally effective against Cys to Ser mutants. One conclusion of these studies. is that upon binding of CAFE to the integrase, nitrogen or sulfur nucleophiles may not be properly situated in the vicinity of the phenethyl aryl ring to allow reaction with and covalent modification of reactive functionality, such as isothiocyanate groups. The fact that introduction of the isothiocyanate group onto various positions of the phenethyl ring or replacement of the phenyl ring with naphthyl rings, failed to significantly affect inhibitory potency, indicates a degree of insensitivity of this region of the molecule toward structural modification. These findings may be useful in future studies concerned with the development and use of HIV-1 integrase affinity ligands. (C) 2001 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(01)00075-x

文献信息

• Preparation of Aryl Isothiocyanates via Protected Phenylthiocarbamates and Application to the Synthesis of Caffeic Acid (4-Isothiocyanato)phenyl Ester
  作者：Xuechun Zhang、Young K. Lee、James A. Kelley、Terrence R. Burke

  DOI：10.1021/jo000139s

  日期：2000.9.1
• Arylisothiocyanate-Containing esters of caffeic acid designed as affinity ligands for HIV-1 integrase
  作者：Xuechun Zhang、Nouri Neamati、Young K Lee、Ann Orr、Ryan D Brown、Noel Whitaker、Yves Pommier、Terrence R Burke

  DOI：10.1016/s0968-0896(01)00075-x

  日期：2001.7

  Integrase is an enzyme found in human immunodeficiency virus, which is required for the viral life cycle, yet has no human cellular homologue. For this reason, HIV integrase (IN) has become an important target for the development of new AIDS therapeutics. Irreversible affinity ligands have proven to be valuable tools for studying a number of enzyme and protein systems. yet to date there have been no reports of such affinity ligands for the study of IN. As an initial approach toward irreversible ligand design directed against IN, we appended isothiocyanate functionality onto caffeic acid phenethyl ester (CAPE), a known HIV integrase inhibitor. The choice of isothiocyanate as the reactive functionality, was based on its demonstrated utility in the preparation of affinity ligands directed against a number of other protein targets. Several isomeric CAFE isothiocyanates were prepared to explore the enzyme topography for reactive nitrogen and sulfur nucleophiles vicinal to the enzyme-bound CAFE. The preparation of these CAFE isothiocyanates. required development of new synthetic methodology which employed phenyl thiocarbamates as latent isothiocyanates which could be unmasked near the end of the synthetic sequence. When it was observed that beta -mercaptoethanol (beta -ME), which is required to maintain the catalytic activity of soluble IN (a F185KC280S mutant), reacted with CAFE isothiocyanate functionality to form the corresponding hydroxyethylthiocarbamate, a variety of mutant IN were examined which did not require the presence of beta -ME for catalytic activity. Although in these latter enzymes, CAFE isothiocyanate functionality was presumed to be present and available for acylation by IN nucleophiles, they were equally effective against Cys to Ser mutants. One conclusion of these studies. is that upon binding of CAFE to the integrase, nitrogen or sulfur nucleophiles may not be properly situated in the vicinity of the phenethyl aryl ring to allow reaction with and covalent modification of reactive functionality, such as isothiocyanate groups. The fact that introduction of the isothiocyanate group onto various positions of the phenethyl ring or replacement of the phenyl ring with naphthyl rings, failed to significantly affect inhibitory potency, indicates a degree of insensitivity of this region of the molecule toward structural modification. These findings may be useful in future studies concerned with the development and use of HIV-1 integrase affinity ligands. (C) 2001 Published by Elsevier Science Ltd.