外消旋N-去丁酰基醋丁洛尔 | 57898-80-3

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 外消旋N-去丁酰基醋丁洛尔
• 中文别名: 醋丁洛尔杂质D
• 英文名称: acetolol
• 英文别名: Deacyl acebutolol；1-[5-amino-2-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]ethanone
• CAS: 57898-80-3
• 化学式: C₁₄H₂₂N₂O₃
• 分子量: 266.34
• InChiKey: DBUJVRULIBQHKT-UHFFFAOYSA-N

物化性质

• 熔点：
  102-104°C
• 沸点：
  468.4±45.0 °C(Predicted)
• 密度：
  1.124±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.6
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 海关编码：
  2922509090

制备方法与用途

N-去丁酰基乙酰丁醇（化合物Ⅲ）是乙酰丁醇（HY-17497）的代谢产物。

反应信息

• 作为反应物：
  描述：

  外消旋N-去丁酰基醋丁洛尔 以34%的产率得到
  参考文献：
  名称：

  HANSON R. N.; HOLMAN B. L.; DAVIS M. A., J. MED. CHEM., 1978, 21, NO 8, 830-833 D2#2#

  摘要：

  DOI：
• 作为产物：
  描述：

  醋丁洛尔 在 盐酸 作用下， 以 水 为溶剂， 反应 5.0h， 生成 外消旋N-去丁酰基醋丁洛尔
  参考文献：
  名称：

  N-芳基酰胺作为化学交换饱和转移磁共振成像造影剂。

  摘要：

  化学交换饱和转移 (CEST) MRI 最近已成为一种通用的分子成像方法，其中可以利用抗磁性化合物生成 MRI 信号。为了扩大 CEST MRI 的应用范围，我们在此系统地研究了具有不同N芳族取代基的N芳基酰胺的 CEST 特性，揭示了它们的化学位移 (4.6–5.8 ppm) 和交换率（高达数千 s -1）与烷基酰胺相比，更适合用作 CEST 试剂。作为第一个概念验证研究，我们使用 CEST MRI 直接通过其固有的 CEST 信号检测药物醋丁洛尔的酶代谢，无需任何化学标记。我们的研究表明N芳基酰胺可能使许多含N-芳基酰胺的药物和作用于N-芳基酰胺的多种酶的代谢的无标记CEST MRI检测成为可能，极大地扩展了CEST MR分子成像的范围。

  DOI：

  10.1002/chem.202002415

文献信息

• A proposed mechanism for the adverse effects of acebutolol: CES2 and CYP2C19-mediated metabolism and antinuclear antibody production
  作者：Kyotaka Muta、Tatsuki Fukami、Miki Nakajima

  DOI：10.1016/j.bcp.2015.09.016

  日期：2015.12

  Acebutolol, a beta-adrenergic receptor-blocker, occasionally causes drug-induced lupus erythematosus (DILE). Acebutolol is mainly metabolized to diacetolol. Because metabolic activation has been considered to be related to acebutolol-induced toxicity, we sought to identify the enzymes that are responsible for acebutolol metabolism and investigate their involvement in acebutolol-induced toxicity. By using human liver microsomes (HLM) or intestinal microsomes and recombinant enzymes, we found that diacetolol was produced via hydrolysis by carboxylesterase 2 (CES2) and subsequent acetylation by N-acetyltransferase 2 (NAT2). When acetolol, a hydrolytic metabolite of acebutolol, was incubated with HLM and an NADPH-generating system, a metabolite conjugated with N-acetylcystein was generated. This metabolite was found to be formed by CYP2C19 based on studies with a panel of recombinant cytochrome P450 enzymes and an inhibition study using HLM with tranylcypromine, a CYP2C19 inhibitor. Because antinuclear antibody (ANA) production is associated with DILE, we investigated whether ANA was detected in plasma from mice treated with acebutolol. Administration of acebutolol (100 mg/kg, p.o.) to female C57BL/6 mice for 30 days resulted in ANA production in plasma in seven of thirteen mice. The number of mice that showed ANA production was larger in mice co-treated with pregnenolone 16 alpha-carbonitrile, an inducer of P450s, whereas it was lower in mice co-treated with tri-o-tolylphosphate or 1-aminobenzotriazole, which are inhibitors of esterases or P450s, respectively. These results suggested that the hydrolysis and oxidation of acebutolol was associated with ANA production. In summary, this study demonstrated that metabolic activation may be a causal factor of adverse reactions of acebutolol. (C) 2015 Elsevier Inc. All rights reserved.
• MAEKI, J.;ROSENQVIST, H.
  作者：MAEKI, J.、ROSENQVIST, H.

  DOI：——

  日期：——