乙巯匹拉嗪 | 1420-55-9

• 物质功能分类: 原料药 - 消化系统用药 - 止吐催吐药
• 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: 乙巯匹拉嗪
• 中文别名: 吐来抗；乙巯拉嗪；硫乙哌丙嗪；硫乙拉嗪
• 英文名称: thiethylperazine
• 英文别名: 2-(ethylthio)-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine；thiethylperazine dimalate；thietylperazine；Torecan；2-ethylsulfanyl-10-[3-(4-methyl-piperazin-1-yl)-propyl]-10H-phenothiazine；2-ethylsulfanyl-10-[3-(4-methylpiperazin-1-yl)propyl]phenothiazine
• CAS: 1420-55-9
• 化学式: C₂₂H₂₉N₃S₂
• 分子量: 399.624
• InChiKey: XCTYLCDETUVOIP-UHFFFAOYSA-N

物化性质

• 熔点：
  62-64°
• 沸点：
  bp0.01 227°
• 密度：
  1.1684 (rough estimate)
• 溶解度：
  DMSO：100 mg/mL（250.24 mM；需要超声波）
• 物理描述：
  Solid
• 颜色/状态：
  Crystals from acetone
• 保留指数：
  3210;3205;3240;3247;3206.9;3238.5;3238.5;3247

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  60.3
• 氢给体数：
  0
• 氢受体数：
  5

ADMET

代谢

原则上，替乙基哌嗪的代谢物与硫利达嗪的代谢物相似。很大一部分剂量以葡萄糖苷酸的形式分泌到胆汁中。

IN PRINCIPLE, METABOLITES OF THIETHYLPERAZINE SIMILAR TO THOSE OF THIORIDAZINE SEEM TO BE FORMED. A LARGE PROPORTION OF THE DOSE IS SECRETED INTO BILE AS GLUCURONIDES.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 甲基化... 是主要由遗传控制的肝微粒体氧化酶和结合过程介导的氧化过程。 /吩噻嗪/

... METAB ... ARE OXIDATIVE PROCESSES MEDIATED LARGELY BY GENETICALLY CONTROLLED HEPATIC MICROSOMAL OXIDASES & CONJUGATION PROCESSES. /PHENOTHIAZINES/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：基于其他吩噻嗪衍生物的最小排泄量，偶尔短期使用甲硫氧嘧啶治疗恶心和呕吐对哺乳婴儿的风险似乎很小。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关已发布信息。 ◉ 对泌乳和母乳的影响：吩噻嗪类药物在26%至40%的女性患者中引起乳汁过多。高催乳素血症似乎是乳汁过多的原因。高催乳素血症是由药物在结节-漏斗通路的多巴胺阻断作用引起的。

◉ Summary of Use during Lactation:Based on minimal excretion of other phenothiazine derivatives, it appears that occasional short-term use of thiethylperazine for the treatment of nausea and vomiting poses little risk to the breastfed infant. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Phenothiazines cause galactorrhea in 26 to 40% of female patients. Hyperprolactinemia appears to be the cause of the galactorrhea. The hyperprolactinemia is caused by the drug's dopamine-blocking action in the tuberoinfundibular pathway.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

与...胍乙啶（阻断抗高血压效果）；吗啡（增强镇静作用）；美沙酮（增加呼吸抑制）；巴比妥类药物和其他中枢神经系统抑制剂，包括酒精（增强作用导致增加的镇静效果或延长的麻醉后睡眠时间）... /马来酸和马来酸盐/

/INTERACTS WITH/...GUANETHIDINE (BLOCKADE OF ANTIHYPERTENSIVE EFFECT); MORPHINE (POTENTIATES SEDATION); MEPERIDINE (INCR RESP DEPRESSION); BARBITURATES & OTHER CNS DEPRESSANTS INCL ALCOHOL (POTENTIATION RESULTING IN INCR SEDATIVE EFFECT OR PROLONGED POST-ANESTHETIC SLEEP TIME)... /MALATE & MALEATE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

与左旋多巴（减少摄取与有效性）相互作用；抗惊厥药（降低癫痫发作阈值）；丙卡巴肼（增强行为异常）。/马来酸和马来酸盐/

/INTERACTS WITH/...LEVODOPA (DECR UPTAKE & EFFECTIVENESS); ANTICONVULSANTS (LOWERS SEIZURE THRESHOLD); PROCARBAZINE (POTENTIATION OF BEHAVIORAL ABNORMALITIES). /MALATE & MALEATE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

迟发性运动障碍是由长期服用硫乙拉嗪引起的。

DYSKINESIA TARDA CAUSED BY LONG-TERM ADMIN OF THIETHYLPERAZINE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 蛋白质结合

百分之六十

60%

来源:DrugBank

吸收、分配和排泄

• 消除途径

替乙酞嗪通过尿液排出。

Thiethylperazine is eliminated in the urine.

来源:DrugBank

吸收、分配和排泄

大约一半的常用吩噻嗪类药物的代谢物在尿液中找到，其余在粪便中。停药6个月后，尿液中仍可检测到各种代谢物。/吩噻嗪类药物/

APPROX HALF OF METABOLITES OF COMMONLY USED PHENOTHIAZINES ARE FOUND IN URINE & REST IN FECES. 6 MO AFTER DISCONTINUATION OF THESE DRUGS, VARIOUS METABOLITES ARE DETECTABLE IN URINE. /PHENOTHIAZINES/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

吩噻嗪类镇静剂迅速穿过胎盘，多年来人们已经在接受治疗的母亲的尿液和新生儿组织中测量到它们，但直到最近才测量到母亲和胎儿体内的血药浓度非常低... /吩噻嗪类/

PHENOTHIAZINE TRANQUILIZERS CROSS PLACENTA RAPIDLY, & THEY HAVE BEEN MEASURED FOR MANY YR IN URINE & TISSUES OF NEONATES OF TREATED MOTHERS, BUT VERY LOW BLOOD LEVELS OF MOTHERS & FETUSES HAVE BEEN MEASURED ONLY RECENTLY... /PHENOTHIAZINES/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

噻乙基拉嗪是一种吩噻嗪衍生物，口服有效，是多巴胺D2受体和组胺H1受体的拮抗剂。此外，它也是一种选择性ABCC1活化剂，能够降低小鼠的淀粉样β（aβ）负荷。噻乙基拉嗪具有止吐、抗精神病以及抗菌作用。

反应信息

• 作为产物：
  描述：

  3-(乙硫基)-N-苯基苯胺 在 sodium hydroxide 、 碘 、 sulfur 、 甲苯 作用下， 生成 乙巯匹拉嗪
  参考文献：
  名称：

  苯并噻嗪-盖比（Shenthesen auf dem Phenothiazin-Gebiet）。2. Mitteilung。N-取代巯基吩噻嗪衍生物

  摘要：

  描述了一系列3-巯基吩噻嗪的药理学上令人感兴趣的N-取代衍生物的合成。

  DOI：

  10.1002/hlca.19580410420

文献信息

• Amino-substituted heterocycles, compositions thereof, and methods of treatment therewith
  申请人：D'Sidocky Neil R.

  公开号：US20080242694A1

  公开（公告）日：2008-10-02

  Provided herein are Heterocyclic Compounds having the following structure: wherein R 1 , R 2 , X, Y and Z are as defined herein, compositions comprising an effective amount of a Heterocyclic Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heterocyclic Compound to a patient in need thereof.

  本文提供具有以下结构的杂环化合物： 其中R1、R2、X、Y和Z如本文所定义，包含有效量杂环化合物的组合物，以及治疗或预防癌症、炎症性疾病、免疫疾病、代谢性疾病以及通过给予患者需要的有效量杂环化合物来抑制激酶途径治疗或预防的疾病的方法。
• [EN] ISOTOPE ENHANCED AMBROXOL FOR LONG LASTING AUTOPHAGY INDUCTION<br/>[FR] AMBROXOL À ISOTOPE AMÉLIORÉ POUR INDUCTION D'AUTOPHAGIE DURABLE
  申请人：STC UNM

  公开号：WO2018148113A1

  公开（公告）日：2018-08-16

  The present invention is directed to 13C and/or 2H isotope enhanced ambroxol ("isotope enhanced ambroxol") and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced amhroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an antophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection. Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer (small cell and non-small cell lung cancer, among other disease states and/or conditions, especially of the lung. Methods of treating autophagy disease states and/or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention. An additional embodiment includes methods of synthesizing compounds according to the present invention as otherwise disclosed herein.

  本发明涉及13C和/或2H同位素增强的氨溴索（“同位素增强的氨溴索”）及其在治疗自噬感染，特别是结核分枝杆菌和其他感染、疾病状态和/或肺部疾病条件中的用途，如肺结核，特别是包括耐药和多重耐药结核病。包括同位素增强的氨溴索的药物组合物，单独或与额外的生物活性剂（特别是利福霉素类抗生素，包括额外的自噬调节剂（一种能够促进或抑制自噬的剂），因此对抗自噬介导的疾病状态和/或条件有用），特别是在肺部发生的自噬介导的疾病状态和/或条件，例如分枝杆菌感染。慢性阻塞性肺病（COPD）、哮喘、肺纤维化、囊性纤维化、干燥综合征和肺癌（小细胞和非小细胞肺癌等其他肺部疾病状态和/或条件，特别是肺部疾病状态和/或条件。治疗自噬疾病状态和/或条件的方法，特别包括治疗主要发生在患者肺部的自噬疾病状态或条件的方法，代表本发明的另一实施例。另一实施例包括根据本发明在此披露的其他方法合成化合物的方法。
• [EN] COMPOUNDS (CYSTEIN BASED LIPOPEPTIDES) AND COMPOSITIONS AS TLR2 AGONISTS USED FOR TREATING INFECTIONS, INFLAMMATIONS, RESPIRATORY DISEASES ETC.<br/>[FR] COMPOSÉS (LIPOPEPTIDES À BASE DE CYSTÉINE) ET COMPOSITIONS EN TANT QU'AGONISTES DES TLR2 UTILISÉS POUR TRAITER DES INFECTIONS, INFLAMMATIONS, MALADIES RESPIRATOIRES ENTRE AUTRES
  申请人：IRM LLC

  公开号：WO2011119759A1

  公开（公告）日：2011-09-29

  The invention provides a novel class of compounds viz. generally lipopeptides like Pam3CSK4, immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors 2. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness a vaccine.

  这项发明提供了一类新型化合物，即一般类似Pam3CSK4的脂肽类化合物，包括含有这类化合物的免疫原组合物和药物组合物，以及使用这类化合物治疗或预防与Toll样受体2相关的疾病或紊乱的方法。在一个方面，这些化合物可用作增强疫苗效果的佐剂。
• Isoindole-imide compounds and compositions comprising and methods of using the same
  申请人：Muller W. George

  公开号：US20070049618A1

  公开（公告）日：2007-03-01

  This invention relates to isoindole-imide compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

  这项发明涉及异吲哚-亚胺化合物，以及它们的药物可接受的盐、溶剂化物、对映异构体和前药。这些化合物的使用方法和药物组合物已经公开。
• PYRIDINE AND PIPERIDINE DERIVATIVES AND USE THEREOF
  申请人：Purdue Pharma L.P.

  公开号：US20150141434A1

  公开（公告）日：2015-05-21

  The invention provides compounds that are useful as sodium channel blockers. In one aspect, the invention provides compounds of Formula I: or pharmaceutically acceptable salts, solvates, hydrates, or diastereomers thereof, wherein R 1 , R 4 , X, G, n, p, W 1 , W 2 , W 3 , W 4 , and the E ring are defined in the disclosure. In certain embodiments, the invention provides compounds of Formulae II-XIII as set forth supra. The invention also provides the use of compounds of any of the above discussed formulae to treat a disorder responsive to blockade of sodium channels. In one embodiment, Compounds of the Invention are useful for treating pain.

  本发明提供了一种用作钠通道阻断剂的化合物。在一方面，本发明提供了公式I的化合物： 或其药用可接受的盐、溶剂化物、水合物或对映异构体，其中R1、R4、X、G、n、p、W1、W2、W3、W4和E环在公开中定义。在某些实施例中，本发明提供了上述公式II-XIII的化合物。本发明还提供了使用上述任何讨论公式的化合物来治疗对钠通道阻断有反应的疾病。在一个实施例中，发明化合物用于治疗疼痛。

表征谱图