盐酸多塞平 | 1229-29-4

• 物质功能分类: 原料药 - 神经系统用药 - 抗抑郁、躁狂药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噁庚英
• 中文名称: 盐酸多塞平
• 中文别名: 盐酸多虑平；盐酸多噻平；多塞平盐酸盐；N,N-二甲基-3-二苯并[B,E]-庚英-11(6H)亚基-丙胺盐酸盐；11-(3-二甲基氨基亚丙基)-6,11-二氢二苯并[b,e]氧杂卓盐酸盐；N,N-二甲基-3-二苯并[b,e]-噁庚英-11(6H)亚基-丙胺盐酸盐
• 英文名称: doxepin hydrochloride
• 英文别名: doxepine hydrochloride；3-(6H-benzo[c][1]benzoxepin-11-ylidene)propyl-dimethylazanium;chloride
• CAS: 1229-29-4
• 化学式: C₁₉H₂₁NO*ClH
• mdl: MFCD00079135
• 分子量: 315.843
• InChiKey: MHNSPTUQQIYJOT-UHFFFAOYSA-N

物化性质

• 熔点：
  187-189°C
• 闪点：
  9℃
• 溶解度：
  可溶于1MHCl：50 mg/mL
• 最大波长(λmax)：
  298nm(lit.)
• 稳定性/保质期：

  将食物存放在-20°C的冷冻室内保存。

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.263
• 拓扑面积：
  12.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  F,T
• 安全说明：
  S36/37/39,S45
• 危险类别码：
  R23/24/25,R39/23/24/25,R25,R11
• WGK Germany：
  1,3
• 海关编码：
  2932999099
• 危险品运输编号：
  UN 2811 6.1/PG 3
• 危险类别：
  6.1(b)
• RTECS号：
  HQ4375000
• 包装等级：
  III
• 储存条件：
  库房应保持通风、低温和干燥，并与食品原料分开存放。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Doxepin HCl
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H301: Toxic if swallowed
H361: Suspected of damaging fertility or the unborn child
P281: Use personal protective equipment as required
P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician
P308+P313: IF exposed or concerned: Get medical advice/attention
P321: Specific treatment (see on this label)
P405: Store locked up

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Section 3. Composition/information on ingredients.
Ingredient name: Doxepin HCl
CAS number: 1229-29-4

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Storage: Store in closed vessels.

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
No data
Boiling point:
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C19H21NO.ClH
Molecular weight: 315.8

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
UN Number: UN2811 Class: 6.1 Packing group: III
Proper shipping name: TOXIC SOLIDS, ORGANIC, N.O.S. (Doxepin HCl)

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

适应症

1. 盐酸多塞平主要用于治疗抑郁症和各种以焦虑抑郁为主的神经症，也可用于更年期精神病。对抑郁和焦虑的躯体性疾病以及慢性酒精性精神疾病也有疗效；此外，还可用于镇静及催眠。
2. 外用膏剂可用于治疗慢性单纯性苔藓、湿疹、过敏性皮炎和特应性皮炎等。

药理作用

盐酸多塞平具有阻断H1和H2受体的作用，并且是胆碱能受体和肾上腺素受体的拮抗剂。其阻断H1受体的效果比苯海拉明强775倍，比安太乐强56倍，比赛庚啶强11倍。研究显示，用本品分别以117mg/kg、83mg/kg和50mg/kg剂量皮肤给药，能够显著抑制右旋糖酐引起的全身性瘙痒，并降低小鼠的皮肤血管通透性；与苯海拉明相比，其效果更强；同时还能抑制磷酸组织胺引起的小鼠过敏反应。对三种过敏模型均表现出较好的量效关系。

不良反应

盐酸多塞平治疗初期可能会出现嗜睡和抗胆碱能反应，如多汗、口干、震颤、眩晕、视物模糊、排尿困难、便秘等。其他不良反应包括皮疹、体位性低血压，偶尔还会引起癫痫发作、骨髓抑制或中毒性肝损伤。

生物活性

盐酸多塞平是一种精神药物，属于三环类抗抑郁药，具有抗焦虑作用。

体外研究

盐酸多塞平能够抑制血清素和去甲肾上腺素的再摄取。对多巴胺的再摄取影响较小。它还对各种受体包括H1、H2、5-HT1、5-HT2、α1-肾上腺素能以及mACh具有拮抗作用。

用途

主要用于抗抑郁症，适用于抑郁症和神经官能症的治疗。

类别

有毒物品

毒性分级

高毒

急性毒性

• 口服：大鼠 LD50: 147 毫克/公斤；小鼠 LD50: 180 毫克/公斤

可燃性危险特性

可燃；燃烧时释放有毒氮氧化物、氯化氢烟雾。药物副作用包括幻觉、偏执、肌肉痉挛、心律改变及耳鸣。

储运特性

库房应通风、低温干燥，与食品原料分开存放。

灭火剂

干粉、泡沫、砂土、二氧化碳以及雾状水均可用于灭火。

反应信息

• 作为反应物：
  描述：

  盐酸多塞平 在 碳酸氢钠 、 三乙胺 、 氯甲酸-2,2,2-三氯乙酯 、 sodium dihydrogenphosphate 、 锌 作用下， 以 二氯甲烷 、 氯仿 、 四氢呋喃 为溶剂， 反应 6.0h， 以45%的产率得到去甲多塞平
  参考文献：
  名称：

  组胺 H1 受体基于肽接头的荧光配体的优化

  摘要：

  组胺 H 1受体 (H 1 R) 最近与介导细胞增殖和癌症进展有关；因此，高亲和力 H 1 R 选择性荧光配体是进一步研究这种体外和体内行为的理想工具。我们之前报道了一种基于拮抗剂 VUF13816 的带有肽接头的H 1 R 荧光配体，并试图进一步探索接头、正构和荧光部分周围的构效关系 (SAR)。在这里，我们报告了一系列高亲和力 H 1R 荧光配体的肽接头组成、正构靶向部分和荧光团各不相同。掺入基于硼-二吡咯甲烯 (BODIPY) 630/650 的荧光团赋予我们的 H 1 R 荧光配体高结合亲和力，显着压倒了在相应未标记同类物中观察到的接头 SAR。化合物31a既有效又具有亚型选择性，可在 10 nM 的浓度下使用共聚焦显微镜实现 H 1 R 可视化。31a与人类 H 1 R的分子对接预测优化的肽接头与受体中的关键残基相互作用。

  DOI：

  10.1021/acs.jmedchem.2c00125
• 作为产物：
  描述：

  2-(溴甲基)苯甲酸乙酯 在 盐酸 、 phosphorus pentoxide 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 盐酸多塞平
  参考文献：
  名称：

  Jalander, Lars; Oksanen, Lasse; Taehtinen, Johanna, Synthetic Communications, 1989, vol. 19, # 19, p. 3349 - 3352

  摘要：

  DOI：

文献信息

• [EN] PYRROLOTRIAZINONE DERIVATIVES AS PI3K INHIBITORS<br/>[FR] DÉRIVÉS DE PYRROLOTRIAZINONE EN TANT QU'INHIBITEURS DES PI3K
  申请人：ALMIRALL SA

  公开号：WO2014060432A1

  公开（公告）日：2014-04-24

  New pyrrolotriazinone derivatives having the chemical structure of formula (I), are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks)

  新的吡咯三唑酮衍生物具有化学结构式（I），公开；以及它们的制备方法，包括它们的药物组合物和它们作为磷脂酰肌醇3-激酶（PI3Ks）抑制剂在治疗中的应用。
• 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。
• Piperazine derivatives and the use thereof as medicament
  申请人：HOENKE Christoph

  公开号：US20150105397A1

  公开（公告）日：2015-04-16

  The present inventions relate to substituted piperazine derivatives of general formula (I) and to the manufacture of said compounds, pharmaceutical compositions comprising a compound according to general formula (I), and the use of said compounds for the treatment of various medical conditions related to glycine transporter-1 (GlyT1).

  这些发明涉及一般式(I)的取代哌嗪衍生物，以及所述化合物的制备，包括符合一般式(I)的化合物的药物组合物，以及利用这些化合物治疗与甘氨酸转运蛋白-1（GlyT1）相关的各种医疗状况。
• New CRTh2 antagonists
  申请人：Almirall, S.A.

  公开号：EP2548876A1

  公开（公告）日：2013-01-23

  The present invention relates to compounds of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by CRTh2 antagonist activity.

  本发明涉及式(I)的化合物，制备这种化合物的方法以及它们在治疗病理状况或疾病中的应用，该病理状况或疾病容易通过CRTh2拮抗活性得到改善。
• Novel Bicyclic Pyridinones
  申请人：Pettersson Martin Youngjin

  公开号：US20120252758A1

  公开（公告）日：2012-10-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药用可接受的盐被披露，其中所述化合物具有如本文所定义的Formula I的结构。相应的药物组合物、治疗方法、合成方法和中间体也被披露。