芥子气 | 505-60-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 芥子气
• 中文别名: 二氯二乙硫醚；二氯乙硫醚；2,2"-二氯乙硫醚
• 英文名称: 1-chloro-2-(2-chloroethylsulfanyl)ethane
• 英文别名: Mustard gas
• CAS: 505-60-2
• 化学式: C₄H₈Cl₂S
• mdl: MFCD00045296
• 分子量: 159.08
• InChiKey: QKSKPIVNLNLAAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  7
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  25.3
• 氢给体数：
  0
• 氢受体数：
  1

ADMET

代谢

硫芥的代谢过程尚未被广泛研究。硫芥倾向于进行分子内环化，形成一种高度活性的化合物。在水溶液中，这种转化过程得到促进，这解释了粘膜组织，如眼睛，对其作用的敏感性。硫芥的环化中间体与富含电子的分子结构反应，并烷基化蛋白质和核酸的巯基（-SH）和氨基（-NH2）基团。代谢途径包括直接的烷基化反应、谷胱甘肽反应、水解和氧化，这些途径是基于在组织中发现的硫芥DNA加合物和尿液中硫芥代谢产物的鉴定而推测出来的。... 在伊朗-伊拉克战争期间，暴露于空气中的硫芥的人的尿液中也发现了硫二甘醇。在两名伊朗-伊拉克战争硫芥中毒受害者的血液中，已经检测到了硫芥的DNA加合物，即N7-HETE-鸟嘌呤的2'-脱氧鸟苷衍生物，N7-(2-羟基乙硫基乙基)-2'脱氧鸟苷，以及硫芥与白蛋白和血红蛋白形成的加合物。....

The metabolism of sulfur mustard has not been studied extensively. Sulfur mustard tends to undergo intramolecular cyclization to create a hyperactive compound. Conversion to this derivative is facilitated in aqueous solution, which accounts for the sensitivity of mucosal tissues, such as the eye, to its action. Sulfur mustard cyclic intermediates react with and alkylate electron-rich molecular structures, such as the sulfhydryl (-SH) and amino (-NH2) groups of proteins and nucleic acids. Metabolic pathways, including direct alkylation reactions, glutathione reactions, hydrolysis, and oxidation, are presumed based on the finding of sulfur mustard DNA adducts in tissues and the identification of urinary products. ... Thiodiglycol was also found in the urine of people exposed to airborne sulfur mustard during the Iran-Iraq. A sulfur mustard adduct in DNA, the 2'-deoxyguanosine derivative of N7-HETE-guanine, N7-(2-hydroxyethylthioethyl)-2'deoxyguanosine, as well as albumin- and hemoglobin-sulfur mustard adducts, have been detected in the blood of two sulfur mustard poisoning victims of the Iran-Iraq War. ....

来源:Hazardous Substances Data Bank (HSDB)

代谢

对伊朗-伊拉克战争中明显有硫芥子气引起的皮肤伤害的伤亡者进行研究，在人类尿液中发现了大量的硫芥子气代谢物，硫二甘醇，这种状况持续了硫芥子气暴露后的长达2周。...在硫芥子气中毒受害者的血液中，已经检测到了DNA、血红蛋白和血清蛋白与硫芥子气的加合物。在两名意外主要皮肤接触硫芥子气的受试者中，检测到硫二甘醇、硫二甘醇亚砜及其密切相关代谢物，包括1,1'-磺酰基双[2-(甲硫基)乙烷]和1-甲硫基-2-[2-甲硫基)乙基磺酰基]乙烷，这些代谢物是由半胱氨酸结合物经过β-裂合酶作用产生的。硫二甘醇亚砜的浓度是硫二甘醇浓度的20到35倍。β-裂合酶的代谢物在尿液中的检测浓度与硫二甘醇亚砜的浓度相当。

Studies of casualties of the Iran-Iraq War with obvious signs of sulfur mustard-induced cutaneous injuries have identified significant amounts of the sulfur mustard metabolite, thiodiglycol, in human urine for up to 2 weeks after sulfur mustard exposure. ... DNA-, hemoglobin- and albumin-sulfur mustard adducts have been detected in the blood of sulfur mustard poisoning victims. In two subjects following an accidental predominantly cutaneous exposure to sulfur mustard, thiodiglycol, thiodiglycol sulfoxide, and closely related metabolites, 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] and 1-methylsulfinyl-2-[2-methylthio) ethylsulfonyl]ethane, derived from the action of beta-lyase on cysteine conjugates, were detected in the urine. Thiodiglycol sulfoxide concentrations were 20 to 35 times thiodiglycol concentrations. The beta-lyase metabolites were detected at concentrations comparable with those of thiodiglycol sulphoxide

来源:Hazardous Substances Data Bank (HSDB)

代谢

...在意外暴露于硫芥蒸汽和气溶胶后，测量了尿液中硫二甘醇的排泄。在暴露于未确定水平后，尿液中可检测到硫二甘醇的水平持续了13天。在暴露后的6个月内随机取样患者的尿液，未检测到进一步的硫二甘醇排泄。硫二甘醇排泄的最大值出现在暴露后的第4天。观察到一级消除动力学，硫二甘醇排泄的半衰期估计为1.2天。

... the excretion of thiodiglycol in human urine /was measured/ following an accidental exposure to sulfur mustard vapor and aerosol. Detectable levels of thiodiglycol in urine were measured for 13 days after exposure to an undetermined level. The patient's urine was randomly sampled for 6 months after exposure and no further thiodiglycol elimination was detected. Maximum thiodiglycol excretion was seen on postexposure day 4. First-order elimination kinetics was observed, and the half-life of thiodiglycol elimination was estimated to be 1.2 days.

来源:Hazardous Substances Data Bank (HSDB)

代谢

吸收后，硫芥发生分子内环化，形成一个乙烯亚磺酸离子中间体，释放出一个自由的氯离子。

After absorption, sulfur mustard undergoes intermolecular cyclization to form an ethylene episulfonium ion intermediate, liberating a free chloride anion.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

致癌性分类：1）人类证据：充分；2）动物证据：有限。对人类致癌风险的总体评估为第1组：该物质对人类致癌。/来自表格/

Classification of carcinogenicity: 1) evidence in humans: sufficient; 2) evidence in animals: limited. Overall summary evaluation of carcinogenic risk to humans is Group 1: The agent is carcinogenic to humans. /From table/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

芥子气：已知是一种人类致癌物。

Mustard gas: known to be a human carcinogen.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：有足够的人类证据证明芥子气的致癌性。芥子气会导致肺癌。此外，芥子气与喉癌之间已经观察到了正相关关系。对于硫芥的致癌性，实验动物中的证据有限。有强烈的证据表明，硫芥的致癌性是通过一种涉及DNA烷基化导致交联形成、抑制DNA合成和修复、点突变以及诱导染色体型和非染色体型畸变的基因毒性机制发挥作用的。硫芥对人体具有致癌性（第1组）。

Evaluation: There is sufficient evidence in humans for the carcinogenicity of mustard gas. Mustard gas causes cancer of the lung. Also, a positive association has been observed between mustard gas and cancer of the larynx, There is limited evidence in experimental animals for the carcinogenicity of sulfur mustard. There is strong evidence that the carcinogenicity of sulfur mustard operates by a genotoxic mechanism of action that involves DNA alkylation leading to cross-link formation, inhibition of DNA synthesis and repair, point mutations, and induction of chromosome-type and chromatid-type aberrations. Sulfur mustard is carcinogenic to humans (Group 1).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

芥子气根据人类研究的致癌性证据被已知为一种人类致癌物。

Mustard gas is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：硫芥

IARC Carcinogenic Agent:Sulfur mustard

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

已经证明，涂抹在皮肤上的80%硫芥会蒸发，10%留在皮肤中，10%被全身吸收。硫芥可以通过接触液体或蒸汽穿透皮肤。穿透速率与剂量、温度和湿度成正比。

It has been demonstrated that 80% of sulfur mustard applied to the skin evaporates, 10% remains in the skin and 10% gets absorbed systemically. It can penetrate the skin by contact with either the liquid or vapor. The rate of penetration is proportional to dose, temperature and humidity.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一名伊朗患者接触芥子气后死亡7天的组织样本中，芥子气的含量通过GC/MS和原子吸收光谱法进行了定性分析。各组织中硫芥的浓度如下：大腿脂肪15.1毫克/千克；大脑10.7毫克/千克；腹部皮肤8.4毫克/千克；肾脏5.6毫克/千克；肌肉3.9毫克/千克；肝脏2.4毫克/千克；脑脊液1.9毫克/升；脾脏1.5毫克/千克；血液1.1毫克/升。

Levels of mustard in the tissues of an Iranian patient who died 7 days after exposure to mustard gas were qualitatively analysed. The concentrations of sulfur mustard determined by GC/MS and atomic absorption spectrophotometer in the tissues were as follows: fat (from thigh) 15.1 mg/kg; brain 10.7 mg/kg; abdominal skin 8.4 mg/kg; kidney 5.6 mg/kg; muscle 3.9 mg/kg; liver 2.4 mg/kg; cerebrospinal fluid 1.9 mg/L; spleen 1.5 mg/kg; blood 1.1 mg/L.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(35)S标记的硫芥在兔子的静脉注射实验中迅速扩散到全身。主要在肝脏、肺和肾脏中保持活性，大约20%的(35)S活性在12小时内被排出。

(35)S-labeled sulfur mustard diffused rapidly throughout the body after intravenous (IV) injection in experiments employing rabbits. Activity was retained chiefly in the liver, lungs, and kidneys, with approximately 20 percent of the (35)S activity being excreted in 12 hours.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

... 硫芥（SM）的毒物动力学以及其主要DNA加合物在雄性无毛豚鼠中通过静脉、呼吸道和皮肤途径进行了研究。该研究包括测量SM在血液中的浓度-时间过程，以及在给药或暴露于SM后，测量完整SM及其与鸟嘌呤加合物在各种组织中的浓度。与磷酸氟酯类神经毒剂相比，SM强烈分布到各种器官，尤其是肺、脾、肝和骨髓。SM的呼吸道毒性似乎是局部的，而不是全身性的。 ...

... /The toxicokinetics of/ sulfur mustard (SM) ... as well as its major DNA-adduct were studied in male hairless guinea pigs for the intravenous, respiratory and percutaneous routes. The study comprised measurement of the concentration-time course of SM in blood and measurement of the concentrations of intact SM and its adduct to guanine in various tissues at several time points after administration of, or exposure to SM. ... In contrast with nerve agents of the phosphofluoridate type, SM partitions strongly to various organs, especially the lung, spleen, liver and bone marrow. The respiratory toxicity of SM appears to be local, rather than systemic. ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 储存条件：
  库房应保持通风、低温和干燥，并将物品与其他氧化剂、食品添加剂及酸类分开存放。

反应信息

• 作为反应物：
  描述：

  芥子气 生成 硫二甘醇
  参考文献：
  名称：

  Ktrordagul Hosny, Al-Ajmi Dhari, J. Environ. Sci. and Health. A, 29 (1994) N 4, S 687-700

  摘要：

  DOI：
• 作为产物：
  描述：

  糠醛 、 ethyldithiocarbazate 在 乙醇 作用下， 生成 芥子气
  参考文献：
  名称：

  Sandstroem, Arkiv foer Kemi, 1952, vol. 4, p. 297,306

  摘要：

  DOI：

文献信息

• [EN] COMPOUNDS THAT MODULATE EGFR ACTIVITY AND METHODS FOR TREATING OR PREVENTING CONDITIONS THEREWITH<br/>[FR] COMPOSÉS MODULANT L'ACTIVITÉ DES RÉCEPTEURS EGFR ET MÉTHODES POUR TRAITER OU PRÉVENIR DES TROUBLES À L'AIDE DE CEUX-CI
  申请人：GATEKEEPER PHARMACEUTICALS INC

  公开号：WO2011140338A1

  公开（公告）日：2011-11-10

  Provided are compounds and methods for treating or preventing kinase-mediated disorders therewith.

  提供了用于治疗或预防激酶介导的疾病的化合物和方法。
• [EN] KINASE INHIBITORS FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS DE KINASE POUR LE TRAITEMENT D'UNE MALADIE
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2015006492A1

  公开（公告）日：2015-01-15

  The invention relates to compounds and their use in the treatment of disease. Novel irreversible inhibitors of wild-type and mutant forms of EGFR, FGFR, ALK, ROS, JAK, BTK, BLK, ITK, TEC, and/or TXK and their use for the treatment of cell proliferation disorders are described.

  这项发明涉及化合物及其在治疗疾病中的应用。描述了用于治疗细胞增殖紊乱的新型EGFR、FGFR、ALK、ROS、JAK、BTK、BLK、ITK、TEC和/或TXK的野生型和突变型不可逆抑制剂及其应用。
• HSP90 Inhibitors Containing a Zinc Binding Moiety
  申请人：Qian Changgeng

  公开号：US20080234297A1

  公开（公告）日：2008-09-25

  The present invention relates to HSP90 inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.

  本发明涉及HSP90抑制剂及其在治疗癌症等细胞增殖性疾病中的应用。所述衍生物还可能作为HDAC抑制剂。
• FUSED AMINO PYRIDINE AS HSP90 INHIBITORS
  申请人：Cai Xiong

  公开号：US20080234314A1

  公开（公告）日：2008-09-25

  The present invention relates to HSP90 inhibitors containing fused amino pyridine core that are useful as inhibitors of HSP90 and their use in the treatment of HSP90 related diseases and disorders such as cancer, an autoimmune disease, or a neurodegenerative disease.

  本发明涉及含有融合氨基吡啶核的HSP90抑制剂，可用作HSP90的抑制剂，以及它们在治疗HSP90相关疾病和紊乱，如癌症、自身免疫疾病或神经退行性疾病中的用途。
• [EN] TREATMENT OR PROPHYLAXIS OF PROLIFERATIVE CONDITIONS<br/>[FR] TRAITEMENT OU PROPHYLAXIE D'ÉTATS PROLIFÉRATIFS
  申请人：UNIV DUNDEE

  公开号：WO2010125350A1

  公开（公告）日：2010-11-04

  The invention relates to novel compounds for use in the treatment or prophylaxis of cancers and other proliferative conditions that are for example characterized by cells that express cytochrome P450 1B1 (CYP1B1) and allelic variants thereof. The invention also provides pharmaceutical compositions comprising one or more such compounds for use in medical therapy, for example in the treatment of prophylaxis of cancers or other proliferative conditions, as well as methods for treating cancers or other conditions in human or non-human animal patients. The invention also provides methods for identifying novel compounds for use in the treatment of prophylaxis of cancers and other proliferative conditions that are for example characterized by cells that express CYP1 B1 and allelic variants thereof. The invention also provides a method for determining the efficacy of a compound of the invention in treating cancer.

  该发明涉及用于治疗或预防癌症和其他增殖性疾病的新化合物，例如这些疾病的特征是细胞表达细胞色素P450 1B1（CYP1B1）及其等位基因变体。该发明还提供包含一种或多种此类化合物的药物组合物，用于医学治疗，例如用于治疗或预防癌症或其他增殖性疾病，以及用于治疗人类或非人类动物患者的癌症或其他疾病的方法。该发明还提供用于识别用于治疗或预防癌症和其他增殖性疾病的新化合物的方法，例如这些疾病的特征是细胞表达CYP1B1及其等位基因变体。该发明还提供一种用于确定该发明中化合物治疗癌症的疗效的方法。

表征谱图