去甲氯丙嗪 | 1225-64-5

• 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 - 有机杂环化合物 - 苯并噻嗪类
• 中文名称: 去甲氯丙嗪
• 中文别名: 氯丙嗪EP杂质D
• 英文名称: Norchlorpromazine
• 英文别名: 2-chloro-N-methyl-10H-phenothiazine-10-propanamine；N-(3-methylaminopropyl)-2-chlorophenothiazine；3-(2-chlorophenothiazin-10-yl)-N-methylpropan-1-amine；3-(2-chloro-10H-phenothiazin-10-yl)-N-methylpropan-1-amine；desmethyl chlorpromazine；[3-(2-chloro-phenothiazin-10-yl)-propyl]-methyl-amine；[3-(2-Chlor-phenothiazin-10-yl)-propyl]-methyl-amin；N-desmethylchlorpromazine
• CAS: 1225-64-5
• 化学式: C₁₆H₁₇ClN₂S
• 分子量: 304.843
• InChiKey: YHFXGBOUSIKGMZ-UHFFFAOYSA-N

物化性质

• 碰撞截面：
  168.7 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
• 保留指数：
  2480

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  40.6
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

氯丙嗪，N-去甲基是氯丙嗪的人类已知代谢物。

Chlorpromazine, N-desmethyl is a known human metabolite of chlorpromazine.

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2934300000
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  去甲氯丙嗪 在 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以30%的产率得到Demethylchlorpromazine sulfoxide
  参考文献：
  名称：

  氯丙嗪及其代谢物的合成及协同抗分枝杆菌筛选†

  摘要：

  单独评估氯丙嗪及其代谢产物的抗分枝杆菌活性，并与抗结核药物联合评估。尽管单独进行试验时氯丙嗪及其代谢产物与有限的抗分枝杆菌活性有关，但与多种氨基糖苷以及利福平，25-去乙酰基利福平的活性代谢物联合检测时，氯丙嗪及其代谢物表现出明显的协同作用。氯丙嗪和壮观霉素的组合具有最大的协同作用，产生的分数抑制浓度指数（FICI）为0.31。7-羟基氯丙嗪或去甲氯丙嗪与卡那霉素，链霉素，大观霉素和25-去乙酰基利福平的组合也观察到协同相互作用（FICI 0.19-0.5）。

  DOI：

  10.1039/c3md00387f
• 作为产物：
  描述：

  盐酸氯丙嗪 在 1,8-双二甲氨基萘 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 3.0h， 生成 去甲氯丙嗪
  参考文献：
  名称：

  NB 06: From a simple lysosomotropic aSMase inhibitor to tools for elucidating the role of lysosomes in signaling apoptosis and LPS-induced inflammation

  摘要：

  Ceramide generation is involved in signal transduction of cellular stress response, in particular during stress-induced apoptosis in response to stimuli such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C-6-ceramide. In this paper we describe 48 diverse synthetic products and evaluate their lysosomotropic and acid sphingomyelinase inhibiting activities in macrophages. A stimuli induced increase of C-16-ceramide in macrophages can be almost completely suppressed by representative compound NB 06 providing an effective protection of macrophages against apoptosis. Compounds like NB 06 thus offer highly interesting fields of application besides prevention of apoptosis of macrophages in atherosclerotic plaques in vessel walls. Most importantly, they can be used for blocking pH dependent lysosomal processes and enzymes in general as well as for analyzing lysosomal dependent cellular signaling. Modulation of gene expression of several prominent inflammatory messengers IL1B, IL6, IL23A, CCL4 and CCL20 further indicate potentially beneficial effects in the field of (systemic) infections involving bacterial endotoxins like LPS or infections with influenza A virus. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.09.021

文献信息

• Radioimmunoassay for Psychotropic Drugs I: Synthesis and Properties of Haptens for Chlorpromazine
  作者：J.W. Hubbard、K.K. Midha、I.J. McGilveray、J.K. Cooper

  DOI：10.1002/jps.2600671118

  日期：1978.11

  the development of radioimmunoassay procedures for chlorpromazine and its active metabolites, three chlorpromazine haptens, 7-(or 8-)(3-carboxypropionyl)chlorpromazine, N-(3-carboxypropionyl)desmethylchlorpromazine, and N-(2-carboxyethyl)desmethylchlorpromazine, were synthesized and characterized by GLC--mass spectrometry, PMR spectrometry, and IR spectrophotometry. Each hapten was coupled to bovine

  为了开发氯丙嗪及其活性代谢物的放射免疫分析方法，使用了三种氯丙嗪半抗原，7-（或8-）（3-羧基丙酰基）氯丙嗪，N-（3-羧基丙酰基）去甲基氯丙嗪和N-（2-羧乙基）去甲基氯丙嗪，合成并通过GLC-质谱，PMR光谱和IR分光光度法进行了表征。将每个半抗原与牛血清白蛋白偶联，并通过UV分光光度法计算每摩尔牛血清白蛋白的半抗原残基数。在兔中获得了每种半抗原-蛋白质缀合物的抗体，并通过评估其与tri化氯丙嗪的结合特性来检查抗血清的效价。
• Investigation of metabolite-protein interactions by transient absorption spectroscopy and in silico methods
  作者：Daniel Limones-Herrero、Fabrizio Palumbo、Victoria Vendrell-Criado、Inmaculada Andreu、Emilio Lence、Concepción González-Bello、Miguel A. Miranda、M. Consuelo Jiménez

  DOI：10.1016/j.saa.2019.117652

  日期：2020.2

  ligand exhibited higher ΔAmax values measured after the laser pulse and were also considerably longer-lived than the non-complexed forms. This is in agreement with an enhanced hydrophilicity of the metabolites, due to the replacement of methyl groups with H that led to a lower extent of protein binding. For the three compounds, laser flash photolysis displacement experiments using warfarin or ibuprofen

  瞬态吸收光谱结合计算机方法已用于研究人血清白蛋白（HSA）与抗精神病药氯丙嗪（CPZ）及其两种脱甲基代谢产物（MCPZ和DCPZ）之间的相互作用。因此，将含有CPZ，MCPZ或DCPZ和HSA（摩尔配体：蛋白质比例为1：0和1：3）的溶液进行激光闪光光解，对应于三重激发态的λ= 470 nm处的ΔAmax为。被监视。在所有情况下，与蛋白质结合的配体在激光脉冲后均显示出较高的ΔAmax值，并且比非复合形式的寿命更长。这与代谢物的亲水性增强相一致，这是由于用H取代了甲基导致了较低程度的蛋白质结合。对于这三种化合物，使用华法令或布洛芬的激光闪光光解置换实验表明，Sudlow位点I为主要结合位点。对接和分子动力学模拟研究表明，两个脱甲基配体与HSA的结合方式将与CPZ显着不同，特别是对于DCPZ，这似乎是由于它们的末端铵基团与氢负键稳定氢键相互作用的能力不同蛋白质袋（Glu153，Glu292）中
• Chemical Synthetic Platform for Chlorpromazine Oligomers That Were Reported as Photo-degradation Products of Chlorpromazine
  作者：Taiki Kohiki、Yusuke Nishikawa、Tsubasa Inokuma、Akira Shigenaga、Akira Otaka

  DOI：10.1248/cpb.c17-00692

  日期：——

  A synthetic platform for chlorpromazine (CPZ) oligomers, which could be generated via photo-reaction of CPZ, is essential to promote their biological and structural studies. In this paper, the first synthetic platform for CPZ oligomers is described. A photo-irradiation experiment of CPZ to confirm whether the structure of the CPZ dimer generated by the photo-irradiation was identical to that prepared by our synthetic method is also reported.

  用于氯丙嗪（CPZ）低聚物的合成平台，可通过CPZ的光反应生成，对于促进它们的生物学和结构研究至关重要。本文首次描述了CPZ低聚物的合成平台，并报道了CPZ的光照射实验，以确认通过光照射生成的CPZ二聚体的结构是否与我们合成方法制备的结构相同。
• The Singlet Oxygen Oxidation of Chlorpromazine and Some Phenothiazine Derivatives. Products and Reaction Mechanisms
  作者：Enrico Baciocchi、Tiziana Del Giacco、Osvaldo Lanzalunga、Andrea Lapi、Daniele Raponi

  DOI：10.1021/jo0706980

  日期：2007.7.1

  and product study of the reactions of chlorpromazine 1, N-methylphenothiazine 2, and N-ethylphenothiazine 3 with singlet oxygen was carried out in MeOH and MeCN. 1 undergoes exclusive side-chain cleavage, whereas the reactions of 2 and 3, in MeOH, afforded only the corresponding sulfoxides. A mechanism for the reaction of 1 is proposed where the first step involves an interaction between singlet oxygen

  在MeOH和MeCN中进行了氯丙嗪1，N-甲基吩噻嗪2和N-乙基吩噻嗪3与单线态氧反应的动力学和产物研究。1在甲醇中仅进行侧链裂解，而2和3的反应仅提供相应的亚砜。提出了1的反应机理，其中第一步涉及单线态氧与侧链二甲基氨基氮之间的相互作用。这就解释了为什么2和3都没有观察到侧链断裂的原因。
• Butyl Methacrylate-Co-Ethylene Glycol Dimethacrylate Monolith for Online in-Tube SPME-UHPLC-MS/MS to Determine Chlopromazine, Clozapine, Quetiapine, Olanzapine, and Their Metabolites in Plasma Samples
  作者：Luiz Beloti、Luis Miranda、Maria Queiroz

  DOI：10.3390/molecules24020310

  日期：——

  This manuscript describes a sensitive, selective, and online in-tube solid-phase microextraction coupled with an ultrahigh performance liquid chromatography-tandem mass spectrometry (in-tube SPME-UHPLC-MS/MS) method to determine chlopromazine, clozapine, quetiapine, olanzapine, and their metabolites in plasma samples from schizophrenic patients. Organic poly(butyl methacrylate-co-ethylene glycol dimethacrylate) monolith was synthesized on the internal surface of a fused silica capillary (covalent bonds) for in-tube SPME. Analyte extraction and analysis was conducted by connecting the monolithic capillary to an UHPLC-MS/MS system. The monolith was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectrometry (FTIR). The developed method presented adequate linearity for all the target antipsychotics: R2 was higher than 0.9975, lack-of-fit ranged from 0.115 to 0.955, precision had variation coefficients lower than 14.2%, and accuracy had relative standard error values ranging from −13.5% to 14.6%, with the exception of the lower limit of quantification (LLOQ). The LLOQ values in plasma samples were 10 ng mL−1 for all analytes. The developed method was successfully applied to determine antipsychotics and their metabolites in plasma samples from schizophrenic patients.

  这篇手稿描述了一种敏感、选择性和在线管内固相微萃取结合超高效液相色谱-串联质谱（管内SPME-UHPLC-MS/MS）方法，用于测定精神分裂症患者血浆样本中氯丙嗪、氯氮平、奎硫平、奥氮平及其代谢物的含量。有机聚合物（丁基甲基丙烯酸酯-乙二醇二甲基丙烯酸酯共聚物）单体在熔融二氧化硅毛细管的内表面上合成（共价键），用于管内SPME。通过将单体毛细管连接到UHPLC-MS/MS系统进行样品提取和分析。单体通过扫描电子显微镜（SEM）和傅里叶变换红外光谱仪（FTIR）进行表征。开发的方法对所有目标抗精神病药物均具有适当的线性关系：R2高于0.9975，缺乏拟合范围为0.115至0.955，精密度的变异系数低于14.2％，准确度的相对标准误差值范围为-13.5％至14.6％，除了定量下限（LLOQ）。血浆样本中的LLOQ值为10 ng mL−1。该方法成功应用于测定精神分裂症患者血浆样本中的抗精神病药物及其代谢物。