flunarizine hydrochloride | 30484-77-6

• 物质功能分类: 原料药 - 循环系统用药 - 周围血管扩张药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: flunarizine hydrochloride
• 英文别名: 1-[bis(4-fluorophenyl)methyl]-4-[(E)-3-phenylprop-2-enyl]piperazine;hydrochloride
• CAS: 30484-77-6
• 化学式: C₂₆H₂₆F₂N₂*ClH
• 分子量: 440.964
• InChiKey: NFKPPSNTQMFDIW-KQGICBIGSA-N

物化性质

• 熔点：
  188-190?C
• 溶解度：
  氯仿/甲醇 (9:1)：50 mg/mL，澄清，无色
• 稳定性/保质期：

  如果按照规格使用和储存，则不会分解，未有已知危险反应。

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  6.5
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R22
• WGK Germany：
  3
• RTECS号：
  TK9187000
• 海关编码：
  2933599090
• 危险标志：
  GHS07
• 危险性描述：
  H302
• 储存条件：
  密封，在2°C至-8°C下保存

SDS

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Section 1. Chemical Product and Company Identification
Flunarizine Dihydrochloride
Common Name/
Trade Name
Flunarizine Dihydrochloride

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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. Get medical attention if irritation occurs.
Skin Contact Wash with soap and water. Cover the irritated skin with an emollient. Get medical attention if irritation develops.
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 Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an
unconscious person. If large quantities of this material are swallowed, call a physician immediately. Loosen tight
clothing such as a collar, tie, belt or waistband.
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.
Risks of explosion of the product in presence of static discharge: Not available.
of Various Substances
SMALL FIRE: Use DRY chemical powder.
Fire Fighting Media
and Instructions LARGE FIRE: Use water spray, fog or foam. Do not use water jet.
As with most organic solids, fire is possible at elevated temperatures Material in powder form, capable of creating
Special Remarks on
a dust explosion.
Fire Hazards
Special Remarks on Explosion Not available.
Hazards

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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 Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water
on the contaminated surface and allow to evacuate through the sanitary system.
Flunarizine Dihydrochloride

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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. Do not store above 8°C(46.4°F).
Refrigerate

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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. (Powdered solid.) Odor Not available.
Taste Not available.
Molecular Weight 477.42 g/mole
Color White.
pH (1% soln/water) Not available.
Not available.
Boiling Point
Melting Point Not available.
Not available.
Critical Temperature
Specific Gravity Not available.
Vapor Pressure Not applicable.
Vapor Density Not available.
Volatility Not available.
Odor Threshold Not available.
Water/Oil Dist. Coeff. Not available.
Ionicity (in Water) Not available.
Dispersion Properties Not available.
Solubility Solubility in CHCl3/Methanol (1:1): 50 mg/ml

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Section 10. Stability and Reactivity Data
The product is stable.
Stability
Instability Temperature Not available.
Conditions of Instability Excess heat, dust generation
Not available.
Incompatibility with various
substances
Not available.
Corrosivity
Flunarizine Dihydrochloride
Not available.
Special Remarks on
Reactivity
Not available.
Special Remarks on
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): 285 mg/kg [Mouse].
Chronic Effects on Humans Not available.
Other Toxic Effects on Slightly hazardous in case of skin contact (irritant), of ingestion, of inhalation.
Humans
Special Remarks on
Not available.
Toxicity to Animals
Special Remarks on May cause adverse reproductive effects and birth defects (teratogenic) based on animal test data.
Chronic Effects on Humans
Special Remarks on other Acute Potential Health Effects:
Toxic Effects on Humans Skin: May cause skin irritation.
Eyes: Dust may cause eye irritation.
Inhalation: Inhalation of dust (poweder) may cause respiratory tract irritation.
Ingestion: May be harmful if swallowed. May cause nausea, vomiting. May affect behavior/central nervous
system (ataxia, somnolence, convulsions), respiration (dyspnea, cyanosis), eyes (ptosis), hair/skin.
Chronic Potential Health Effects:
Ingestion: Prolonged or repeated ingestion may cause nausea, vomiting, weight loss, convulsions.

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Section 12. Ecological Information
Ecotoxicity Not available.
BOD5 and COD Not available.
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

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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).
Identification Not applicable.
Not applicable.
Special Provisions for
Transport
Flunarizine Dihydrochloride
DOT (Pictograms)

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Section 15. Other Regulatory Information and Pictograms
No products were found.
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 (EINECS No.
250-216-6).
Canada: Not listed on Canadian Domestic Substance List (DSL) or Canadian Non-Domestic Substances List
(NDSL)
China: Not listed on National Inventory.
Japan: Not listed on National Inventory (ENCS).
Korea: Not listed on National Inventory (KECI).
Philippines: Not listed on National Inventory (PICCS).
Australia: Listed on AICS.
Other Classifications WHMIS (Canada) Not controlled under WHMIS (Canada).
DSCL (EEC) R22- Harmful if swallowed. S46- If swallowed, seek medical advice
immediately and show this container or label.
Health Hazard
HMIS (U.S.A.) 1 National Fire Protection
1 Flammability
1 Association (U.S.A.)
Fire Hazard
1 0 Reactivity
Health
Reactivity
0
Specific hazard
Personal Protection
E
WHMIS (Canada)
(Pictograms)
DSCL (Europe)
(Pictograms)
TDG (Canada)
(Pictograms)
ADR (Europe)
(Pictograms)
Protective Equipment
Gloves.
Flunarizine Dihydrochloride
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

理化性质

盐酸氟桂利嗪是一种钙通道阻断剂，属于双氧化哌嗪衍生物。它能有效防止因病理性钙超载导致的细胞受损。尽管近十年相关文献报道不多，但由于其在偏头痛、耳鸣和椎基底动脉疾病治疗中的良好功效与安全性，仍有必要进一步研究。

生物活性

Flunarizine 2HCl（KW-3149, R14950）是一种二氢盐酸盐，能够抑制钙离子通道，其Ki值为68 nM。

目标	值
钙离子通道	68 nM(Ki)

化学性质

盐酸氟桂利嗪是一种血管扩张药，主要用于治疗动脉硬化、脑血管痉挛、脑栓塞、冠状动脉硬化及末梢循环不良等疾病。

用途

• 生产盐酸氟桂利嗪胶囊的主要成分
• 治疗脑血管疾病

反应信息

• 作为反应物：
  描述：

  α-环糊精 、 flunarizine hydrochloride 以 water-d2 为溶剂， 生成
  参考文献：
  名称：

  A comparative study of inclusion complexes of flunarizine with alpha (α-CD) and beta-cyclodextrin (β-CD)

  摘要：

  对氟拉嗪（FL）与α-和β-CD 的络合进行了详细的核磁共振（1H、COSY 和 ROESY）光谱研究。1H NMR 滴定研究证实了 FL/α-CD 和 FL/β-CD 复合物的形成，CD 和 FL 的质子共振的化学位移变化证明了这一点。复合物的化学计量比被确定为 1:2（FL/α-CD）和 1:1（FL/β-CD），总体结合常数也被计算出来。借助 ROESY 光谱数据证实，在络合过程中，只有一个 F 取代的芳香环和苯环穿透了 α-CD 空腔，而两个 F 取代的芳香环和苯环都穿透了 β-CD 空腔。从 ROESY 实验数据得出的 FL/CD 空腔相互作用的结合模式表明，与 α-CD 相比，FL 与 β-CD 形成的复合物具有更好的诱导配合作用，这也是与 α-CD 相比，β-CD 分子稳定性更强的原因。客体渗入 CD 空腔的方式和复合物的结构已经确定。

  DOI：

  10.1007/s10847-010-9809-1

文献信息

• SELF-ASSEMBLY OF THERAPEUTIC AGENT-PEPTIDE NANOSTRUCTURES
  申请人：Ohio State Innovation Foundation

  公开号：US20140155577A1

  公开（公告）日：2014-06-05

  Disclosed are conjugates of hydrophobic drugs linked to protected or unprotected amino acids or peptides. The disclosed conjugates are amphiphilic and can self assemble into nanotubes. Nanotubes comprising the conjugates are also described and can have high loading of the drug and protect it from degradation or elimination. The nanotubes are well suited to deliver hydrophobic and unstable drugs to individuals.

  揭示了与受保护或未受保护的氨基酸或肽连接的疏水药物的共轭物。所述的共轭物是两性的，可以自组装成纳米管。还描述了包含这些共轭物的纳米管，可以具有高药物载荷并保护药物免受降解或排泄。这些纳米管非常适合向个体输送疏水和不稳定的药物。
• COMPOSITIONS SOUS FORME D'UNE SOLUTION AQUEUSE INJECTABLE COMPRENANT DU GLUCAGON HUMAIN ET UN CO-POLYAMINOACIDE
  申请人：ADOCIA

  公开号：US20190275156A1

  公开（公告）日：2019-09-12

  Physically stable compositions in the form of an injectable aqueous solution, wherein the pH is from 6.0 to 8.0, includes at least: a) human glucagon and b) a co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy. In one embodiment, the compositions further comprise a gut hormone.

  在形式为可注射的水溶液中，具有稳定的物理性质，其中pH值为6.0至8.0，至少包括： a) 人类胰高血糖素和 b) 具有羧酸基团和疏水基团Hy的共聚氨基酸。在一个实施例中，这些组合物进一步包括一种肠道激素。
• Multi-functional ionic liquid compositions for overcoming polymorphism and imparting improved properties for active pharmaceutical, biological, nutritional, and energetic ingredients
  申请人：Rogers D. Robin

  公开号：US20070093462A1

  公开（公告）日：2007-04-26

  Disclosed are ionic liquids and methods of preparing ionic liquid compositions of active pharmaceutical, biological, nutritional, and energetic ingredients. Also disclosed are methods of using the compositions described herein to overcome polymorphism, overcome solubility and delivery problems, to control release rates, add functionality, enhance efficacy (synergy), and improve ease of use and manufacture.

  揭示了离子液体及制备活性药物、生物、营养和能量成分的离子液体组合物的方法。还揭示了利用本文描述的组合物的方法，以克服多型性、克服溶解度和输送问题、控制释放速率、增加功能性、增强功效（协同作用）以及改善易用性和制造工艺。
• COMPOSITIONS IN THE FORM OF AN INJECTALE AQUEOUS SOLUTION COMPRISING HUMAN GLUCAGON AND A CO-POLYAMINO ACID
  申请人：ADOCIA

  公开号：US20190275110A1

  公开（公告）日：2019-09-12

  Physically stable compositions in the form of an injectable aqueous solution, the pH of which is comprised from 6.0 to 8.0, having at least: human glucagon and a co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy, in one embodiment, the compositions according to the invention further includes a gastrointestinal hormone.

  物理上稳定的组合物以可注射的水溶液形式存在，其pH值为6.0至8.0，至少包括：人胰高血糖素和带有羧基电荷和疏水基团Hy的共聚氨基酸，在一种实施方式中，根据本发明的组合物进一步包括肠道激素。
• [EN] DUAL FUNCTIONING IONIC LIQUIDS AND SALTS THEREOF<br/>[FR] LIQUIDES IONIQUES À DOUBLE FONCTION ET SELS DE CEUX-CI
  申请人：UNIV ALABAMA

  公开号：WO2010078300A1

  公开（公告）日：2010-07-08

  Disclosed herein are ionic liquid compositions comprising active pharmaceutical, biological, and nutritional compounds, and methods of use. Further disclosed are compositions of matter including liquid ion pairs alone or in solution and their use; compositions of ionic liquids that are 'solvated,' for example, 'hydrated' and their uses.

  本文揭示了包括活性药物、生物学和营养化合物的离子液体组合物，以及其使用方法。进一步揭示了包括液态离子对的物质组合物，单独或溶解后使用；以及离子液体的“溶剂化”组合物，例如“水合”的组合物及其用途。