马来酸罗托沙敏 | 3505-38-2

• 物质功能分类: 原料药 - 抗变态反应药 - 抗组胺药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 马来酸罗托沙敏
• 中文别名: 卡比沙明马来酸盐；N-[2-[(4-氯苯基)(2-吡啶基)甲氧基]乙基]-N,N-二甲基胺马来酸盐；马来酸卡比沙明
• 英文名称: carbinoxamine maleate
• 英文别名: carbinoxamine maleate salt；(Z)-but-2-enedioic acid;2-[(4-chlorophenyl)-pyridin-2-ylmethoxy]-N,N-dimethylethanamine
• CAS: 3505-38-2
• 化学式: C₄H₄O₄*C₁₆H₁₉ClN₂O
• 分子量: 406.866
• InChiKey: GVNWHCVWDRNXAZ-BTJKTKAUSA-N

物化性质

• 熔点：
  116-1180C
• 溶解度：
  氯仿：微溶；甲醇：微溶
• 碰撞截面：
  167.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  3.11
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  7

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间的使用总结：偶尔小剂量的卡比沙明在哺乳期间可能是可接受的。较大剂量或更长时间的使用可能会导致婴儿昏昏欲睡或其他影响，或者减少奶量，尤其是与伪麻黄碱等拟交感神经药联合使用或在母乳建立良好之前。制造商建议在卡比沙明使用期间避免哺乳，因为2岁以下儿童中发生了严重毒性反应。首选的替代品是非镇静抗组胺药。 ◉ 对哺乳婴儿的影响：没有报告母亲使用卡比沙明治疗期间哺乳的婴儿。在一项电话随访研究中，母亲报告有10%的婴儿接触到各种抗组胺药后出现烦躁和腹痛症状，1.6%的婴儿出现嗜睡。所有反应均无需医疗注意。 ◉ 对泌乳和母乳的影响：在非哺乳期妇女和产后早期妇女中，相对高剂量的抗组胺药通过注射可以降低基础血清催乳素。然而，催乳素分泌不受产后母亲抗组胺药预处理的影响。尚未研究较低口服剂量的卡比沙明是否对血清催乳素有相同的影响，或者催乳素的影响是否对哺乳成功有任何影响。在已经建立哺乳的母亲中，催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:Small occasional doses of carbinoxamine are probably acceptable during breastfeeding. Larger doses or more prolonged use may cause drowsiness and other effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. The manufacturer recommends avoiding breastfeeding during carbinoxamine use because severe toxicity has occurred in children under 2 years. The nonsedating antihistamines are preferred alternatives. ◉ Effects in Breastfed Infants:There are no reports of infants breastfed during maternal therapy with carbinoxamine. In one telephone follow-up study, mothers reported irritability and colicky symptoms in 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention. ◉ Effects on Lactation and Breastmilk:Antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of carbinoxamine have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

来源:Drugs and Lactation Database (LactMed)

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  T
• 安全说明：
  S26,S36/37/39,S45
• 危险类别码：
  R25
• WGK Germany：
  3
• 海关编码：
  2933399090
• 危险品运输编号：
  UN 3249
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 储存条件：
  库房应保持通风、低温和干燥，并与食品原料分开储运。

SDS

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Section 1. Chemical Product and Company Identification
Carbinoxamine, Maleate Salt
Common Name/
Trade Name
Carbinoxamine, Maleate Salt

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Section 3. Hazards Identification
Potential Acute Health Effects Hazardous in case of ingestion. Slightly hazardous in case of skin contact (irritant), of eye contact (irritant), of
inhalation (lung irritant). Severe over-exposure can result in death.
Potential Chronic Health CARCINOGENIC EFFECTS: Not available.
Effects MUTAGENIC EFFECTS: Not available.
TERATOGENIC EFFECTS: Not available.
DEVELOPMENTAL TOXICITY: Not available.
The substance may be toxic to central nervous system (CNS).
Repeated or prolonged exposure to the substance can produce target organs damage. Repeated exposure to a
highly toxic material may produce general deterioration of health by an accumulation in one or many human
organs.

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Section 4. First Aid Measures
Eye Contact Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at
least 15 minutes. Cold water may be used. Get medical attention.
Skin Contact In case of contact, immediately flush skin with plenty of water. Cover the irritated skin with an emollient. Remove
contaminated clothing and shoes. Cold water may be used.Wash clothing before reuse. Thoroughly clean shoes
before reuse. Get medical attention.
Serious Skin Contact Not available.
Inhalation If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get
medical attention.
Serious Inhalation Not available.
Ingestion If swallowed, do not induce vomiting unless directed to do so by medical personnel. Never give anything by
mouth to an unconscious person. Loosen tight clothing such as a collar, tie, belt or waistband. Get medical
attention immediately.
Serious Ingestion Not available.

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Section 5. Fire and Explosion Data
Flammability of the Product May be combustible at high temperature.
Auto-Ignition Temperature Not available.
Flash Points Not available.
Flammable Limits Not available.
Products of Combustion These products are carbon oxides (CO, CO2), nitrogen oxides (NO, NO2...), halogenated compounds.
Fire Hazards in Presence of Slightly flammable to flammable in presence of heat.
Various Substances
Explosion Hazards in Presence Risks of explosion of the product in presence of mechanical impact: Not available.
of Various Substances Slightly explosive in presence of open flames and sparks.
Fire Fighting Media SMALL FIRE: Use DRY chemical powder.
and Instructions LARGE FIRE: Use water spray, fog or foam. Do not use water jet.
Special Remarks on As with most organic solids, fire is possible at elevated temperatures
Fire Hazards
Special Remarks on Explosion Fine dust dispersed in air in sufficient concentrations, and in the presence of an ignition source is a potential dust
Hazards explosion hazard.
Carbinoxamine, Maleate Salt

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Section 6. Accidental Release Measures
Small Spill Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by
spreading water on the contaminated surface and dispose of according to local and regional authority
requirements.
Large Spill Poisonous solid.
Stop leak if without risk. Do not get water inside container. Do not touch spilled material. Use water spray to
reduce vapors. Prevent entry into sewers, basements or confined areas; dike if needed. Eliminate all ignition
allow to evacuate through the sanitary system.

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Section 7. Handling and Storage
Precautions Keep away from heat. Keep away from sources of ignition. Ground all equipment containing material. Do not
ingest. Do not breathe dust. Wear suitable protective clothing. If ingested, seek medical advice immediately and
show the container or the label.
Storage Keep container tightly closed. Keep container in a cool, well-ventilated area.

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Section 8. Exposure Controls/Personal Protection
Engineering Controls Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below
recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to
airborne contaminants below the exposure limit.
Personal Protection
Safety glasses. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves.
Personal Protection in Case of Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used
a Large Spill to avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist
BEFORE handling this product.
Exposure Limits Not available.

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Section 9. Physical and Chemical Properties
Physical state and appearance Solid. (Crystalline powder.) Odorless.
Odor
Taste Not available.
Molecular Weight 406.9 g/mole
Color White.
pH (1% soln/water) Not available.
Boiling Point Not available.
Melting Point Not available.
Critical Temperature Not available.
Not available.
Specific Gravity
Vapor Pressure Not applicable.
Not available.
Vapor Density
Volatility Not available.
Not available.
Odor Threshold
Water/Oil Dist. Coeff. Not available.
Ionicity (in Water) Not available.
Dispersion Properties See solubility in water.
Solubility Easily soluble in cold water.
Carbinoxamine, Maleate Salt

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Section 10. Stability and Reactivity Data
The product is stable.
Stability
Instability Temperature Not available.
Excess heat
Conditions of Instability
Not available.
Incompatibility with various
substances
Corrosivity Not available.
Special Remarks on Not available.
Reactivity
Special Remarks on Not available.
Corrosivity
Polymerization Will not occur.

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Section 11. Toxicological Information
Routes of Entry Inhalation. Ingestion.
Toxicity to Animals Acute oral toxicity (LD50): 162 mg/kg [Mouse].
Chronic Effects on Humans May cause damage to the following organs: central nervous system (CNS).
Other Toxic Effects on Hazardous in case of ingestion.
Humans Slightly hazardous in case of skin contact (irritant), of inhalation (lung irritant).
Special Remarks on Not available.
Toxicity to Animals
Special Remarks on Not available.
Chronic Effects on Humans
Special Remarks on other Acute Potential Health Effects:
Toxic Effects on Humans Skin: It may cause skin irritation.
Eyes: It may cause eye irritation.
Inhalation: It may cause respiratory tract irritation, shortness of breath/trouble breathing.
Ingestion: Harmful if swallowed. May cause dryness of the mouth, nose, throat. flushiness or redness of face.
May affect behavior/central nervous system (hallucinations, distorted perceptions, excitement, drowsiness,
clumsiness, unsteadiness), respiration (shortness of breath/trouble breathing).
Chronic Potential Health Effects:
Possible hypersensitization/allergic anaphylactic reaction to dust if inhaled, ingested or in contact with skin.

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Section 12. Ecological Information
Not available.
Ecotoxicity
Not available.
BOD5 and COD
Products of Biodegradation Possibly hazardous short term degradation products are not likely. However, long term degradation products may
arise.
Toxicity of the Products The products of degradation are as toxic as the product itself.
of Biodegradation
Special Remarks on the Not available.
Products of Biodegradation
Carbinoxamine, Maleate Salt

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Section 13. Disposal Considerations
Waste Disposal Waste must be disposed of in accordance with federal, state and local environmental
control regulations.

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Section 14. Transport Information
DOT Classification Not a DOT controlled material (United States).
Not applicable.
Identification
Not applicable.
Special Provisions for
Transport
DOT (Pictograms)

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Section 15. Other Regulatory Information and Pictograms
TSCA 8(b) inventory: Carbinoxamine, Maleate Salt
Federal and State
Regulations
California California prop. 65: This product contains the following ingredients for which the State of California has found
to cause cancer which would require a warning under the statute: No products were found.
Proposition 65
Warnings
California prop. 65: This product contains the following ingredients for which the State of California has found
to cause birth defects which would require a warning under the statute: No products were found.
Other Regulations OSHA: Hazardous by definition of Hazard Communication Standard (29 CFR 1910.1200).
EINECS: This product is on the European Inventory of Existing Commercial Chemical Substances.
WHMIS (Canada) Not available
Other Classifications
DSCL (EEC) R22- Harmful if swallowed. S26- In case of contact with eyes, rinse
R36/37/38- Irritating to eyes, immediately with plenty of water and seek
respiratory system and skin. medical advice.
S36/37- Wear suitable protective clothing and
gloves.
S46- If swallowed, seek medical advice
immediately and show this container or label.
Health Hazard
HMIS (U.S.A.) 2 National Fire Protection
1 Flammability
1 Association (U.S.A.)
Fire Hazard
2 0 Reactivity
Health
Reactivity
0
Specific hazard
Personal Protection
E
WHMIS (Canada)
(Pictograms)
DSCL (Europe)
(Pictograms)
Carbinoxamine, Maleate Salt
TDG (Canada)
(Pictograms)
ADR (Europe)
(Pictograms)
Protective Equipment
Gloves.
Lab coat.
Dust respirator. Be sure to use an
approved/certified respirator or
equivalent.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Carbinoxamine maleate是一种组胺-H1受体阻滞剂，具有抗组胺和反副交感神经生理作用。

靶点

Target	Value
Histamine H1 receptor	()

类别

• 有毒物质
• 毒性分级：高毒
• 急性毒性：
  • 口服-小鼠LD50: 162毫克/公斤
  • 皮下-小鼠LD50: 350毫克/公斤

危险特性

• 可燃；火场释放有毒氮氧化物、氯化物烟雾
• 储运特性：库房通风低温干燥；与食品原料分开储运
• 灭火剂：水、二氧化碳、泡沫、沙土

文献信息

• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。
• CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
  申请人：Parion Sciences, Inc.

  公开号：US20140171447A1

  公开（公告）日：2014-06-19

  This invention provides compounds of the formula I: and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.

  这项发明提供了式I的化合物及其药用盐，可用作钠通道阻滞剂，包含这些化合物的组合物，以及用于这些化合物的治疗方法和用途，以及制备这些化合物的方法。
• Dual Pharmacophores - PDE4-Muscarinic Antagonistics
  申请人：Callahan James Francis

  公开号：US20090203657A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.

  本发明涉及具有式（I）的新化合物及其药用盐，药物组合物及其用作对PDE4和肌胆碱受体（mAChRs）具有抑制活性的双色素，因此可用于治疗呼吸道疾病。
• [EN] DUAL PHARMACOPHORES - PDE4-MUSCARINIC ANTAGONISTICS<br/>[FR] PHARMACOPHORES DUALS, ANTAGONISTES DES RÉCEPTEURS MUSCARINIQUES ET INHIBITEURS DE L'ACTIVITÉ PDE4
  申请人：GLAXO GROUP LTD

  公开号：WO2009100169A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula's (I) - (VI), and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of and/or prophylaxis of respiratory diseases, including inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.

  本发明涉及式(I) - (VI)的新化合物，以及其药学上可接受的盐、药物组合物及其在治疗中的应用，例如作为磷酸二酯酶IV (PDE4)的抑制剂和肌碱乙酰胆碱受体 (mAChRs)的拮抗剂，用于治疗和/或预防呼吸道疾病，包括炎症性和/或过敏性疾病，如慢性阻塞性肺病（COPD）、哮喘、鼻炎（例如过敏性鼻炎）、特应性皮炎或银屑病。
• Azabicycloalkane compounds
  申请人：——

  公开号：US20040242622A1

  公开（公告）日：2004-12-02

  This invention provides compounds of formula I: 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both &bgr; 2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Such compounds are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

  这项发明提供了式I的化合物： 其中R1、R2、R3、R4、R5、R6和R7如规范中所定义，或其药用可接受盐、溶剂或立体异构体。本发明的化合物具有β2肾上腺素受体激动剂和肌碱受体拮抗剂活性。这些化合物对治疗肺部疾病，如慢性阻塞性肺病和哮喘，是有用的。