盐酸甲氧氮芥 | 302-70-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 盐酸甲氧氮芥
• 英文名称: mechlorethamine oxide hydrochloride
• 英文别名: nitromin；bis-(2-chloro-ethyl)-methyl-amine oxide; hydrochloride；Bis-(2-chlor-aethyl)-methyl-aminoxid; Hydrochlorid；N,N-Bis-(2-chlor-aethyl)-N-methyl-hydroxylaminium-chlorid, Bis-(2-chlor-aethyl)-hydroxy-methyl-ammonium-chlorid；2-chloro-N-(2-chloroethyl)-N-methylethanamine oxide;hydron;chloride
• CAS: 302-70-5
• 化学式: C₅H₁₁Cl₂NO*ClH
• 分子量: 208.515
• InChiKey: SYNHCENRCUAUNM-UHFFFAOYSA-N

物化性质

• 熔点：
  109-110°
• 颜色/状态：
  Prisms from acetone
• 气味：
  ODORLESS
• 溶解度：
  Sol in water
• 分解：
  When heated to decomposition it emits toxic fumes of /Hydrogen Chloride and Nitrogen Oxides/.

计算性质

• 辛醇/水分配系数(LogP)：
  1.83
• 重原子数：
  10
• 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：
  18.1
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

毒理性

• 毒性总结

毒理学效应：糜烂性物质会影响身体的内外部。它们会引起炎症、水疱和组织的普遍破坏。蒸气对身体的湿润区域影响更大。眼睛尤其容易受到糜烂性物质的伤害。吸入糜烂性物质会导致肺膜肿胀并充满液体（肺水肿）。可能导致缺氧死亡。糜烂性物质也是全身性药剂，容易通过皮肤影响包括生产血液的组织在内的易感组织。氮基糜烂性物质应被视为致癌物。暴露途径：糜烂性物质通过吸入、皮肤和眼睛接触、摄入以及擦伤的皮肤（例如，皮肤破裂或被碎片刺穿）具有危害。/糜烂性物质 - 氮基/

Toxicology Effects: Vesicants affect both exterior and interior parts of the body. Vesicants cause inflammation, blisters, and general destruction of tissues. Vapors have a greater impact on moist areas of the body. Eyes are especially susceptible to vesicants. Inhalation of Vesicants can cause lung membranes to swell and become filled with liquid (pulmonary edema). Death may result from lack of oxygen. Vesicants are also systemic agents and readily pass through the skin to affect susceptible tissue including those that produce blood. Nitrogen Vesicants should be considered carcinogenic. Pathways: Vesicants are hazardous through inhalation, skin and eye exposure, ingestion, and abraded skin (e.g., breaks in the skin or penetration of skin by debris). /Vesicants- Nitrogen Based/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

潜伏期：暴露于氮基糜烂性毒剂后，组织损伤可能在几分钟内发生，但临床效果可能需要长达24小时才显现。眼部刺激可能立即发生。由于吸入该剂蒸汽导致的肺水肿可能会延迟数小时出现。/糜烂性毒剂 - 基于氮的/

Latency Period: Tissue damage occurs within minutes of exposure to Nitrogen Vesicants, but clinical effects may not appear for up to 24 hours. Eye irritation may develop immediately. Pulmonary edema caused by inhalation of the agent vapor may be delayed for several hours. /Vesicants - Nitrogen Based/

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：无足够数据；2）动物证据：充分。对人类致癌风险的总体评估为2B组：该物质可能对人类致癌。/氮芥N-氧化物；来自表格/

Classification of carcinogenicity: 1) evidence in humans: no adequate data; 2) evidence in animals: sufficient. Overall summary evaluation of carcinogenic risk to humans is Group 2B: The agent is possibly carcinogenic to humans. /Nitrogen mustard N-oxide; from table/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

肝动脉内注入氮芥N-氧化物（10或20毫克/千克）并系统给药胱氨酸（500毫克/千克）在大鼠肝肿瘤中控制肿瘤生长。仅通过肝动脉输注氮芥N-氧化物的大鼠全部死亡。

COMBINED INFUSION OF NITROGEN MUSTARD N-OXIDE (10 OR 20 MG/KG) INTO HEPATIC ARTERY ALONG WITH SYSTEMIC ADMIN OF CYSTEINE (500 MG/KG) IN SARCOMA BEARING RATS, CONTROLLED TUMOR GROWTH IN LIVER. ALL RATS RECEIVING ONLY NITROGEN MUSTARD N-OXIDE BY INFUSION INTO HEPATIC ARTERY DIED.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

急救：迹象与症状：轻微蒸汽暴露可能不会产生皮肤损伤。有一个无症状潜伏期（4到24小时），随后皮肤出现炎症和发红，进而发展为水泡。眼睛影响，包括刺激、流泪和对光敏感可能会立即出现。也可能有眼睛炎症。大量蒸汽会导致眼睑肿胀。眼睛疼痛可能导致痉挛，最终导致眼睛闭合。上呼吸道症状因暴露量而异，包括鼻刺激、喉咙沙哑、喉炎和感觉呼吸困难。/糜烂性物质 - 基于氮的/

First Aid: Signs & Symptoms: Mild vapor exposure may not produce skin lesions. There is an asymptomatic latent period (4 to 24 hours) followed by inflammation and redness of the skin progressing to blisters. Eye impacts, including irritation, tearing, and sensitivity to light may appear immediately. There may also be inflammation of the eyes. Larger amounts of vapor cause swelling of the eyelids. Pain in the eyes may cause spasms and eventually cause the eyes to close. Upper respiratory signs vary with the amount of exposure and include nasal irritation, scratchy throat, laryngitis, and a feeling of shortness of breath. /Vesicants - Nitrogen Based/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在狗体内静脉注射5毫克/千克体重的（14）C标记的甲基氮芥N-氧化物后...血液中在1小时后无活性...在尿液中，最高放射性水平在注射后5至20分钟之间发现，并且在4小时后降至0。

After iv injection of 5 mg/kg body wt (14)C-labeled-methyl nitrogen mustard N-oxide in dogs ... no activity ... in blood after 1 hr in urine, highest level of radioactivity was found between 5 & 20 min after injection & had declined to 0 after 4 hr.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 海关编码：
  2921199090
• 包装等级：
  II
• 危险类别：
  6.1(a)
• 危险品运输编号：
  UN 3249

制备方法与用途

类别：有毒物质
毒性分级：高毒
急性毒性：

• 口服（大鼠）LD50：60毫克/公斤
• 腹腔（小鼠）LD50：125毫克/公斤

可燃性危险特性：热分解产生有毒的氮氧化物和氯化物烟雾

储运特性：库房低温、通风干燥；与食品原料分开存放

灭火剂：水、二氧化碳、干粉、泡沫

反应信息

• 作为反应物：
  描述：

  盐酸甲氧氮芥 在 水 、 silver(l) oxide 作用下， 生成 2-[(2-chloro-ethyl)-methyl-aminooxy]-ethanol
  参考文献：
  名称：

  Owari, Pharmaceutical Bulletin, 1953, vol. 1, p. 353,357

  摘要：

  DOI：

文献信息

• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。
• [EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020006722A1

  公开（公告）日：2020-01-09

  A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.

  一种新型的交联细胞毒剂，吡咯苯并二氮杂环二聚体（PBD）衍生物，以及它们与细胞结合分子的结合物，一种制备这些结合物的方法以及这些结合物的治疗用途。
• CYCLIC ETHER PYRAZOL-4-YL-HETEROCYCLYL-CARBOXAMIDE COMPOUNDS AND METHODS OF USE
  申请人：Genentech, Inc.

  公开号：US20140088117A1

  公开（公告）日：2014-03-27

  Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds of Formula I, including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein R 2 is a cyclic ether and X is thiazolyl, pyrazinyl, pyridinyl, or pyrimidinyl, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式I的环醚吡唑-4-基-杂环基-羧酰胺化合物，包括立体异构体、几何异构体、互变异构体和其药学上可接受的盐，其中R2为环醚，X为噻唑基、吡啶基、吡啶基或嘧啶基，可用于抑制Pim激酶，并用于治疗由Pim激酶介导的癌症等疾病。公开了使用公式I化合物进行体外、体内和体内诊断、预防或治疗哺乳动物细胞中的这类疾病或相关病理条件的方法。
• [EN] ASH1L INHIBITORS AND METHODS OF TREATMENT THEREWITH<br/>[FR] INHIBITEURS DE ASH1L ET MÉTHODES DE TRAITEMENT AU MOYEN DE CEUX-CI
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2017197240A1

  公开（公告）日：2017-11-16

  Provided herein are small molecule inhibitors of ASH1L activity and small molecules that facilitate ASH1L degradation and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.

  本文提供了ASH1L活性的小分子抑制剂，促进ASH1L降解的小分子以及它们的使用方法，用于治疗疾病，包括急性白血病、实体肿瘤和其他依赖于ASH1L活性的疾病。
• [EN] COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF<br/>[FR] COMPOSÉS COMPRENANT UN LIEUR CLIVABLE ET LEURS UTILISATIONS
  申请人：INTOCELL INC

  公开号：WO2019008441A1

  公开（公告）日：2019-01-10

  Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.

  提供了一种包括可切割连接物的化合物，其用途，以及用于制备该化合物的中间体化合物，更具体地，本发明的包括可切割连接物的化合物可能包括具有特定功能或活性的活性剂（例如，药物，毒素，配体，用于检测的探针等），能够选择性释放活性剂的SO2官能团，以及通过外部刺激触发化学反应，物理化学反应和/或生物反应的官能团，并且还可以包括具有与所需靶受体结合特异性的配体（例如，寡肽，多肽，抗体等）。