盐酸曲唑酮杂质43 | 220910-12-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 盐酸曲唑酮杂质43
• 英文名称: 2-(3-((2-((3-chlorophenyl)amino)ethyl)amino)propyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one
• 英文别名: 2-[3-[2-(3-chloroanilino)ethylamino]propyl]-[1,2,4]triazolo[4,3-a]pyridin-3-one
• CAS: 220910-12-3
• 化学式: C₁₇H₂₀ClN₅O
• 分子量: 345.832
• InChiKey: SGXXTUPUUQQXFD-UHFFFAOYSA-N

物化性质

• 沸点：
  523.0±60.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  60
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  氯乙酸乙酯 、 盐酸曲唑酮杂质43 在 sodium hydride 、 三乙胺 作用下， 生成 2-{3-[4-(3-Chloro-phenyl)-3-oxo-piperazin-1-yl]-propyl}-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one
  参考文献：
  名称：

  Effect of Modifications of the Alkylpiperazine Moiety of Trazodone on 5HT_2A and α₁ Receptor Binding Affinity

  摘要：

  A series of triazolopyridine derivatives (compounds 2a-I) were synthesized in order to-explore the effect of modifications of the alkylpiperazine moiety of trazodone (fragment A) on binding affinity for 5HT(2A) and alpha(1) receptors. All of the synthesized compounds show a decrease of affinity for both 5HT(2A) and alpha(1) receptors, as compared to trazodone, with the exception of compounds 2b,c which bear a methyl group in an alpha position to the aliphatic nitrogen atom N-1. These compounds showed a decrease of affinity only for the alpha(1) receptor. The stereochemical influence of the piperazine moiety of compound 2c was also evaluated. Enantiomer (S)-2c showed the most significant differences between 5HT(2A) and alpha(1) receptor affinity (IC50 values) and among the corresponding functional properties (pA(2) values). Since (S)-2c cannot generate the metabolite 4-(3-chlorophenyl)piperazine this product was selected for further pharmacological studies.

  DOI：

  10.1021/jm970700n
• 作为产物：
  描述：

  盐酸曲唑酮 在 盐酸 、 水 作用下， 反应 24.0h， 生成 2-(3-(4-(3,5-dichlorophenyl)piperazin-1-yl)propyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one 、 盐酸曲唑酮杂质43
  参考文献：
  名称：

  UHPLC方法在曲唑酮主要光解降解产物的LC-MS和NMR分离和表征中的应用†

  摘要：

  药物降解产物是一种会影响药物安全性的药物杂质。曲唑酮（TZD）是一种抗抑郁药，按照ICH嵌入式指南中的预测药物降解产物的规定，会被迫降解。它在酸性水解，过氧化物诱导的氧化中以及在暴露于日光下会发生降解，并导致形成十种降解产物（DPs）。开发了UHPLC方法，使用Acquity UPLC CSH C 18色谱柱的固定相（100×2.1 mm，1.7μm）和溶剂-A的流动相（10 mM醋酸铵，pH 8.5）分离TZD及其DP。溶剂B（甲醇）的流速为0.25 mL min -1在梯度洗脱中。将该方法转移到四极杆飞行时间串联质谱仪（QTOF-MS / MS）上以鉴定DP。非常有趣的是，在光解降解条件下发现了四个二聚体DP，并且发现它们是异构体。使用制备型HPLC分离主要异构体（DP-10），并使用质子和碳NMR鉴定其结构。三N还观察到氧化DPs，并通过大气压化学电离质谱法（APCI-MS）鉴定了N

  DOI：

  10.1039/c8nj03545h

文献信息

• Effect of Modifications of the Alkylpiperazine Moiety of Trazodone on 5HT_2A and α₁ Receptor Binding Affinity
  作者：Marilena Giannangeli、Nicola Cazzolla、Maria Rita Luparini、Maurizio Magnani、Massimo Mabilia、Giuseppe Picconi、Mauro Tomaselli、Leandro Baiocchi

  DOI：10.1021/jm970700n

  日期：1999.2.1

  A series of triazolopyridine derivatives (compounds 2a-I) were synthesized in order to-explore the effect of modifications of the alkylpiperazine moiety of trazodone (fragment A) on binding affinity for 5HT(2A) and alpha(1) receptors. All of the synthesized compounds show a decrease of affinity for both 5HT(2A) and alpha(1) receptors, as compared to trazodone, with the exception of compounds 2b,c which bear a methyl group in an alpha position to the aliphatic nitrogen atom N-1. These compounds showed a decrease of affinity only for the alpha(1) receptor. The stereochemical influence of the piperazine moiety of compound 2c was also evaluated. Enantiomer (S)-2c showed the most significant differences between 5HT(2A) and alpha(1) receptor affinity (IC50 values) and among the corresponding functional properties (pA(2) values). Since (S)-2c cannot generate the metabolite 4-(3-chlorophenyl)piperazine this product was selected for further pharmacological studies.
• Application of the UHPLC method for separation and characterization of major photolytic degradation products of trazodone by LC-MS and NMR
  作者：Mohit Thummar、Prinesh N. Patel、Bhoopendra Singh Kushwah、Gananadhamu Samanthula

  DOI：10.1039/c8nj03545h

  日期：——

  Drug degradation products are a type of drug impurity which affects the safety of the drug products. Trazodone (TZD) is an antidepressant drug subjected to forced degradation as per ICH embedded guidelines for predicting the drug degradation products. It undergoes degradation in acidic hydrolysis, peroxide induced oxidation and upon exposure to day light and results in the formation of ten degradation

  药物降解产物是一种会影响药物安全性的药物杂质。曲唑酮（TZD）是一种抗抑郁药，按照ICH嵌入式指南中的预测药物降解产物的规定，会被迫降解。它在酸性水解，过氧化物诱导的氧化中以及在暴露于日光下会发生降解，并导致形成十种降解产物（DPs）。开发了UHPLC方法，使用Acquity UPLC CSH C 18色谱柱的固定相（100×2.1 mm，1.7μm）和溶剂-A的流动相（10 mM醋酸铵，pH 8.5）分离TZD及其DP。溶剂B（甲醇）的流速为0.25 mL min -1在梯度洗脱中。将该方法转移到四极杆飞行时间串联质谱仪（QTOF-MS / MS）上以鉴定DP。非常有趣的是，在光解降解条件下发现了四个二聚体DP，并且发现它们是异构体。使用制备型HPLC分离主要异构体（DP-10），并使用质子和碳NMR鉴定其结构。三N还观察到氧化DPs，并通过大气压化学电离质谱法（APCI-MS）鉴定了N