N,N-二甲基-3-(5-氧代-10H-吩噻嗪-10-基)-1-丙胺 | 146-21-4

• 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: N,N-二甲基-3-(5-氧代-10H-吩噻嗪-10-基)-1-丙胺
• 中文别名: 比阿培南杂质；丙嗪亚砜
• 英文名称: promazine sulfoxide
• 英文别名: Promazine 5-sulfoxide；10-(3-(N,N-dimethylamino)-1-propyl)-10H-phenothiazine-5-oxide；sulfoxyde de promazine；promazina solfossido；promazine-S-oxide；N,N-dimethyl-3-(5-oxophenothiazin-10-yl)propan-1-amine
• CAS: 146-21-4
• 化学式: C₁₇H₂₀N₂OS
• 分子量: 300.425
• InChiKey: KSHDHDWHIWBNHA-UHFFFAOYSA-N

物化性质

• 熔点：
  114 - 116°C
• 溶解度：
  氯仿（微溶）、二氯甲烷（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  53.5
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

Promazine 5-sulfoxide 是 promazine 的一个已知人体代谢物。

Promazine 5-sulfoxide is a known human metabolite of promazine.

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2934300000

反应信息

• 作为反应物：
  描述：

  N,N-二甲基-3-(5-氧代-10H-吩噻嗪-10-基)-1-丙胺 、 碘甲烷 以 苯 为溶剂， 反应 24.0h， 以96%的产率得到10-(3-(trimethylammonio)-1-propyl)-10H-phenothiazine-5-oxide iodide
  参考文献：
  名称：

  N-取代氧化吩噻嗪的制备及电化学行为

  摘要：

  The chemical properties of promazine oxide (Prom-O) and promazine (Prom) were compared. Cyclic voltammetry (CV) experiments showed a higher oxidation potential of Prom-O compared to that of Prom. The results of CV measurements also suggested the potential applicability of Prom-O as an n-type semiconductor.

  DOI：

  10.3987/com-16-13437
• 作为产物：
  描述：

  丙嗪 在 水 作用下， 以 硫酸 为溶剂， 生成 N,N-二甲基-3-(5-氧代-10H-吩噻嗪-10-基)-1-丙胺
  参考文献：
  名称：

  锰(III)配合物在磷酸盐酸性介质中歧化和氧化降解吩噻嗪衍生物的机理研究

  摘要：

  在大量过量的焦磷酸锰 (P2O72−)、磷酸根 (PO43−) 和 H+ 离子存在下，使用 UV-vis 研究了锰 (III) 对吩噻嗪衍生物 (PTZ) 的氧化降解。光谱学。第一个不可逆步骤是吩噻嗪和焦磷酸锰之间的快速反应，导致完全转化为稳定的吩噻嗪自由基。在第二步中，阳离子自由基被锰氧化成双阳离子，然后水解成吩噻嗪 5-氧化物。反应速率受锰（III）离子的配位和稳定性控制，这些离子受这些离子的还原电位及其对许多还原剂的氧化能力强的影响。阳离子自由基也可能在另一个竞争反应中转化为最终产物。最终产品，吩噻嗪 5-氧化物，也是通过歧化反应形成的。由于第一步和进一步过程的速率差异很大，因此可以在酸性磷酸盐介质中研究氧化降解的第二步的动力学。对于吩噻嗪自由基的降解，建立了伪一级速率常数 (kobs) 对具有显着非零截距的 [MnIII] 的线性依赖性。在分离方法中使用的锰 (III) 复合物的过量浓度范围内，该速率取决于

  DOI：

  10.1007/s11243-011-9531-x

文献信息

• Contribution of human cytochrome<i>P</i>-450 isoforms to the metabolism of the simplest phenothiazine neuroleptic promazine
  作者：Jacek Wójcikowski、Lydiane Pichard-Garcia、Patrick Maurel、Władysława A Daniel

  DOI：10.1038/sj.bjp.0705195

  日期：2003.4

  The aim of the present study was to identify human cytochrome P‐450 isoforms (CYPs) involved in 5‐sulphoxidation and N‐demethylation of the simplest phenothiazine neuroleptic promazine in human liver. The experiments were performed in the following in vitro models: (A) a study of promazine metabolism in liver microsomes—(a) correlations between the rate of promazine metabolism and the level and activity of CYPs; (b) the effect of specific inhibitors on the rate of promazine metabolism (inhibitors: CYP1A2—furafylline, CYP2D6—quinidine, CYP2A6+CYP2E1—diethyldithiocarbamic acid, CYP2C9—sulfaphenazole, CYP2C19—ticlopidine, CYP3A4—ketoconazole); (B) promazine biotransformation by cDNA‐expressed human CYPs (Supersomes 1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2E1, 3A4); (C) promazine metabolism in a primary culture of human hepatocytes treated with specific inducers (rifampicin—CYP3A4, CYP2B6 and CYP2C inducer, 2,3,7,8‐tetrachlordibenzeno‐p‐dioxin (TCDD)—CYP1A1/1A2 inducer). In human liver microsomes, the formation of promazine 5‐sulphoxide and N‐desmethylpromazine was significantly correlated with the level of CYP1A2 and ethoxyresorufin O‐deethylase and acetanilide 4‐hydroxylase activities, as well as with the level of CYP3A4 and cyclosporin A oxidase activity. Moreover, the formation of N‐desmethylpromazine was correlated well with S‐mephenytoin 4′‐hydroxylation. Furafylline (a CYP1A2 inhibitor) and ketoconazole (a CYP3A4 inhibitor) significantly decreased the rate of promazine 5‐sulphoxidation, while furafylline and ticlopidine (a CYP2C19 inhibitor) significantly decreased the rate of promazine N‐demethylation in human liver microsomes. The cDNA‐expressed human CYPs generated different amounts of promazine metabolites, but the rates of CYP isoforms to catalyse promazine metabolism at therapeutic concentration (10 μM) was as follows: 1A1>2B6>1A2>2C9>3A4>2E1>2A6>2D6>2C19 for 5‐sulphoxidation and 2C19>2B6>1A1>1A2>2D6>3A4>2C9>2E1>2A6 for N‐demethylation. The highest intrinsic clearance (Vmax/Km) was found for CYP1A subfamily, CYP3A4 and CYP2B6 in the case of 5– sulphoxidation, and for CYP2C19, CYP1A subfamily and CYP2B6 in the case of N‐demethylation. In a primary culture of human hepatocytes, TCDD (a CYP1A subfamily inducer), as well as rifampicin (mainly a CYP3A4 inducer) induced the formation of promazine 5‐sulphoxide and N‐desmethylpromazine. Regarding the relative expression of various CYPs in human liver, the obtained results indicate that CYP1A2 and CYP3A4 are the main isoforms responsible for 5‐sulphoxidation, while CYP1A2 and CYP2C19 are the basic isoforms that catalyse N‐demethylation of promazine in human liver. Of the other isoforms studied, CYP2C9 and CYP3A4 contribute to a lesser degree to promazine 5‐sulphoxidation and N‐demethylation, respectively. The role of CYP2A6, CYP2B6, CYP2D6 and CYP2E1 in the investigated metabolic pathways of promazine seems negligible. British Journal of Pharmacology (2003) 138, 1465–1474. doi:10.1038/sj.bjp.0705195

  本研究的目的是在人类肝脏中确定参与简单吩噻嗪抗精神病药物普罗迷嗪（promazine）5-硫氧化和N-脱甲基作用的人类细胞色素P-450异构体（CYPs）。 实验是在以下体外模型中进行的：(A) 研究普罗迷嗪在肝微粒体中的代谢——(a) 普罗迷嗪代谢速率与CYPs的水平和活性的相关性；(b) 特异性抑制剂对普罗迷嗪代谢速率的影响（抑制剂：CYP1A2—呋拉西林，CYP2D6—金鸡纳碱，CYP2A6 + CYP2E1—二乙基二硫代碳酸盐，CYP2C9—磺胺苯唑，CYP2C19—噻氯匹啶，CYP3A4—酮康唑）；(B) cDNA表达的重组人CYPs催化普罗迷嗪的生物转化（使用的CYPs为Supersomes 1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2E1, 3A4）；(C) 在人原代肝细胞培养物中，普罗迷嗪在特定诱导剂处理下的代谢（利福霉素——CYP3A4、CYP2B6和CYP2C诱导剂，2,3,7,8-四氯二苯并-dioxin（TCDD）——CYP1A1/1A2诱导剂）。 在人肝微粒体中，普罗迷嗪5-硫氧化物和N-脱甲基普罗迷嗪的形成与CYP1A2的水平以及乙氧基苦味酸O-脱乙基酶和对硝基苯酚N-羟化酶的活性显著相关，同时也与CYP3A4的水平和环孢素A氧化酶的活性显著相关。此外，N-脱甲基普罗迷嗪的形成与S-甲乙双键酶的活性良好相关。 呋拉西林（CYP1A2抑制剂）和酮康唑（CYP3A4抑制剂）显著降低了普罗迷嗪5-硫氧化的速率，而呋拉西林和噻氯匹啶（CYP2C19抑制剂）显著降低了人肝微粒体中普罗迷嗪N-脱甲基的速率。 cDNA表达的人CYPs生成了不同量的普罗迷嗪代谢物，但在治疗浓度（10 μM）下，各CYP异构体催化普罗迷嗪代谢的速率如下：5-硫氧化为1A1 > 2B6 > 1A2 > 2C9 > 3A4 > 2E1 > 2A6 > 2D6 > 2C19；N-脱甲基为2C19 > 2B6 > 1A1 > 1A2 > 2D6 > 3A4 > 2C9 > 2E1 > 2A6。在5-硫氧化中，CYP1A亚家族、CYP3A4和CYP2B6具有最高的固有清除率（V_max/K_m）；在N-脱甲基中，CYP2C19、CYP1A亚家族和CYP2B6具有最高的固有清除率。 在人原代肝细胞培养物中，TCDD（CYP1A亚家族诱导剂）以及利福霉素（主要是CYP3A4诱导剂）诱导了普罗迷嗪5-硫氧化物和N-脱甲基普罗迷嗪的形成。 根据各种CYP在人类肝脏中的相对表达水平，结果显示CYP1A2和CYP3A4是负责5-硫氧化的主要异构体，而CYP1A2和CYP2C19是催化普罗迷嗪N-脱甲基作用的基本异构体。在研究的其他异构体中，CYP2C9和CYP3A4分别对普罗迷嗪的5-硫氧化和N-脱甲基作用有较小的贡献。CYP2A6、CYP2B6、CYP2D6和CYP2E1在普罗迷嗪研究代谢途径中的作用似乎可以忽略不计。 British Journal of Pharmacology (2003) 138, 1465–1474. doi:10.1038/sj.bjp.0705195
• Formation of a promazine radical and promazine 5-oxide in the reaction of promazine with hydrogen peroxide: Mechanistic insight from kinetic and EPR measurements
  作者：Joanna Wiśniewska、Grzegorz Wrzeszcz、Stanisław Koter

  DOI：10.1002/kin.20454

  日期：2010.1

  The kinetics of the oxidation of promazine (PMZ) by hydrogen peroxide was studied in the presence of a large excess of H2O2 in acidic chloride media using UV–vis spectroscopy. The reaction proceeds via two consecutive steps. In the first step, oxidation leads to formation of a promazine radical. In the second step, the promazine radical is oxidized to promazine 5‐oxide. Electron paramagnetic resonance

  使用紫外可见光谱法研究了在酸性氯化物介质中大量过量的H 2 O 2存在下过氧化氢对异丙嗪（PMZ）的氧化动力学。反应通过两个连续步骤进行。在第一步中，氧化导致丙嗪基的形成。在第二步中，丙嗪自由基被氧化为丙嗪5-氧化物。电子顺磁共振波谱（EPR）结果为中间体丙嗪基团的形成提供了清晰的证据。伪一阶速率常数（k 1和k 2）对[H 2 O 2的线性依赖性分别为第一和第二过程建立了具有非零截距的]。反应第一阶段的速率随O 2浓度的增加而略有增加，表明OH •自由基在氧化还原过程中的作用，这些自由基被转化为Cl自由基。在所有这些动力学测量的基础上讨论了整个反应的机理。©2009 Wiley Periodicals，Inc.国际化学杂志Kinet 42：1–9，2010
• Mild and Selective Oxygenation of Sulfides to Sulfoxides and Sulfones by Perfluoro-cis-2,3-dialkyloxaziridines
  作者：Darryl D. DesMarteau、Viacheslav A. Petrov、Vittorio Montanari、Massimo Pregnolato、Giuseppe Resnati

  DOI：10.1021/jo00089a020

  日期：1994.5

  Sulfides are oxidized to sulfoxides by stoichiometric amounts of perfluoro-cis-2,3-dialkyloxaziridines 2. The reactions proceed at -40 degrees C with nearly complete selectivity and very good yields. Sulfoxides are also oxidized easily by 2 under mild conditions to corresponding sulfones. The oxidation of some bioactive sulfides (promazine, albendazole, biotin, and others) is also reported.
• Aminoalkylphenothiazines
  作者：Robert Bruce Moffett、Brooke D. Aspergren

  DOI：10.1021/ja01492a022

  日期：1960.4
• Barret; Pautet; Daudon, Pharmazie, 1986, vol. 41, # 4, p. 285 - 286
  作者：Barret、Pautet、Daudon

  DOI：——

  日期：——