4-(acetylamino)phenyl ethyl carbonate | 17243-26-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(acetylamino)phenyl ethyl carbonate
• 英文别名: 4-ethyloxycarbonyloxyacetanilide；1-acetylamino-4-ethoxycarbonyloxy-benzene；(4-Acetamino-phenyl)-kohlensaeure-aethylester；1-Acetylamino-4-aethoxycarbonyloxy-benzol；4-Acetaminophenyl-aethylcarbonat；4-Acetamidophenylethylcarbonat；4-Acetamidophenyl ethyl carbonate；(4-acetamidophenyl) ethyl carbonate
• CAS: 17243-26-4
• 化学式: C₁₁H₁₃NO₄
• 分子量: 223.229
• InChiKey: AXHGKAOXRWHBIF-UHFFFAOYSA-N

物化性质

• 熔点：
  121.5°C
• 沸点：
  364.51°C (rough estimate)
• 密度：
  1.2446 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对乙酰氨基酚 、 氯甲酸乙酯 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 以45%的产率得到4-(acetylamino)phenyl ethyl carbonate
  参考文献：
  名称：

  酯酶的特异性和前药酯的结构：各种酰化对乙酰氨基酚化合物和乙酰氨基苯甲酸酯化合物的反应性。

  摘要：

  测量了对乙酰氨基苯甲酸的各种酯（APAB）和各种酰化的对乙酰氨基酚（APAP）衍生物的酶催化水解的相对速率。检查了中性，阴离子和阳离子酯。所采用的酶来源是大鼠肠匀浆，大鼠肝匀浆，大鼠血浆和部分纯化的商业酶。在APAB和APAP酯中，中性酯是所检查酶中最敏感的酶，其敏感性归因于碳链长度。APAB酯在酶学上比APAP酯稳定。这些酯的相对水解速率取决于酶的来源。在大鼠肠匀浆中，结构识别能力良好，但在大鼠血浆中则较弱。

  DOI：

  10.1002/jps.2600771009

文献信息

• Overcoming steric effects in the coupling reaction of alkyloxycarbonyloxymethyl (AOCOM) halides with phenols: an efficient synthesis of AOCOM phenolic prodrugs
  作者：Joshua D. Thomas、Kenneth B. Sloan

  DOI：10.1016/j.tetlet.2006.10.160

  日期：2007.1

  Steric hindrance is a key factor in the coupling reaction of AOCOM halides with phenols. Sterically unhindered alkoxy groups favor the formation of acylated phenol. Under phase-transfer conditions, alkylated phenol is favored regardless of steric hindrance.

  立体位阻是AOCOM卤化物与酚类偶联反应的关键因素。立体上不受阻碍的烷氧基有利于酰化苯酚的形成。在相转移条件下，无论空间位阻如何，烷基化苯酚都是有利的。
• Topical Delivery of a Model Phenolic Drug: Alkyloxycarbonyl Prodrugs of Acetaminophen
  作者：Scott C. Wasdo、Kenneth B. Sloan

  DOI：10.1023/b:pham.0000029281.12753.25

  日期：2004.6

  Purpose. To determine whether the delivery of a phenolic parent drug by its alkyloxycarbonyl (AOC) prodrugs through hairless mouse skin would show similar dependencies on water and lipid solubilities that similar prodrugs of more polar heterocyclic amide and imide parent drugs have shown.Methods. Flux through hairless mouse skin from suspensions in isopropyl myristate (J(MIPM)), solubilities in IPM (S-IPM) and water (S-AQ), and partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K-IPM:4.0) were measured for two series of AOC derivatives of acetaminophen ( APAP); their solubilities in pH 4.0 buffer (S-4.0) were estimated from S-IPM/K-IPM:4.0. Log J(MIPM) values were calculated from the n = 43 coefficients for the parameters in the transformed Potts-Guy (Roberts-Sloan) equation, and the average error of prediction (Delta log J'(IPM)) was calculated. The J(MIPM), S-IPM, S-4.0, and molecular weight ( MW) data for this series and two other series were combined with the n = 43 database to give a n = 61 database, and new best fit coefficients were determined for the Roberts-Sloan equation: log J(MIPM) = x + y log S-IPM + (1 - y) log S-4.0 - z MW.Results. All of the 4-AOC-APAP derivatives underperformed based on their predicted log J(MIPM) (Delta log J'(MIPM) = 0.275 +/- 0.147 log units) and, although the two more water soluble members of this more lipid soluble series were more effective than APAP, they were only marginally so: <2 times. Addition of three new series to the n = 43 database for the Roberts-Sloan equation did not substantially change the coefficients to the parameters: x, y, z, and r(2) = -0.322, 0.530, 0.00337 and 0.92, respectively.Conclusions. The topical delivery of a model phenolic drug by its AOC prodrugs through hairless mouse skin from IPM shows the same dependence on S-IPM, S-4.0, and MW as the delivery of polar heterocycles by their similar prodrugs.
• DE85803
  申请人：——

  公开号：——

  公开（公告）日：——
• Hinsberg, Justus Liebigs Annalen der Chemie, 1899, vol. 305, p. 287
  作者：Hinsberg

  DOI：——

  日期：——
• Specificity of Esterases and Structure of Prodrug Esters: Reactivity of Various Acylated Acetaminophen Compounds and Acetylaminobenzoated Compounds
  作者：Hiromitsu Seki、Takeo Kawaguchi、Takeru Higuchi

  DOI：10.1002/jps.2600771009

  日期：1988.10

  catalyzed hydrolysis of various esters of p-acetylaminobenzoic acid (APAB) and variously acylated acetaminophen (APAP) derivatives were measured. Neutral, anionic, and cationic esters were examined. The enzyme sources adopted were rat intestinal homogenate, rat liver homogenate, rat plasma, and a partly purified commercial enzyme. In both APAB and APAP esters, neutral esters were the most sensitive

  测量了对乙酰氨基苯甲酸的各种酯（APAB）和各种酰化的对乙酰氨基酚（APAP）衍生物的酶催化水解的相对速率。检查了中性，阴离子和阳离子酯。所采用的酶来源是大鼠肠匀浆，大鼠肝匀浆，大鼠血浆和部分纯化的商业酶。在APAB和APAP酯中，中性酯是所检查酶中最敏感的酶，其敏感性归因于碳链长度。APAB酯在酶学上比APAP酯稳定。这些酯的相对水解速率取决于酶的来源。在大鼠肠匀浆中，结构识别能力良好，但在大鼠血浆中则较弱。