托可拉斯 | 23142-01-0

• 物质功能分类: 原料药 - 呼吸系统用药 - 镇咳药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 托可拉斯
• 中文别名: 柠檬酸喷托维林；枸橼酸喷托维林；妥克拉司；咳必清
• 英文名称: carbetapentane citrate
• 英文别名: pentoxyverine citrate；2-[2-(diethylamino)ethoxy]ethyl 1-phenylcyclopentane-1-carboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid
• CAS: 23142-01-0
• 化学式: C₆H₈O₇*C₂₀H₃₁NO₃
• mdl: MFCD00055697
• 分子量: 525.596
• InChiKey: AKJDEXBCRLOVTH-UHFFFAOYSA-N

物化性质

• 熔点：
  84-86?C
• 溶解度：
  可溶于水中
• 稳定性/保质期：
  在常温常压下，该物质保持稳定。

计算性质

• 辛醇/水分配系数(LogP)：
  3.97
• 重原子数：
  37
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.615
• 拓扑面积：
  171
• 氢给体数：
  4
• 氢受体数：
  11

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S26,S36
• 危险类别码：
  R20/21/22,R36/37/38
• WGK Germany：
  3
• 海关编码：
  2922509090
• 储存条件：
  将物品存放在密封的容器中，并储存在阴凉、干燥的地方。

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Carbetapentane citrate salt
CAS-No. : 23142-01-0
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP]
Acute toxicity, Inhalation (Category 4)
Acute toxicity, Dermal (Category 4)
Acute toxicity, Oral (Category 4)
Skin irritation (Category 2)
Eye irritation (Category 2)
Specific target organ toxicity - single exposure (Category 3)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Harmful by inhalation, in contact with skin and if swallowed. Irritating to eyes, respiratory system and skin.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Warning
Hazard statement(s)
H302 Harmful if swallowed.
H312 Harmful in contact with skin.
H315 Causes skin irritation.
H319 Causes serious eye irritation.
H332 Harmful if inhaled.
H335 May cause respiratory irritation.
Precautionary statement(s)
P261 Avoid breathing dust/ fume/ gas/ mist/ vapours/ spray.
P280 Wear protective gloves/ protective clothing.
P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
Supplemental Hazard none
Statements
Safety data sheet available on request.
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R20/21/22 Harmful by inhalation, in contact with skin and if swallowed.
R36/37/38 Irritating to eyes, respiratory system and skin.
S-phrase(s)
S26 In case of contact with eyes, rinse immediately with plenty of water and
seek medical advice.
S36 Wear suitable protective clothing.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : 1-Phenylcyclopentanecarboxylic acid 2-(2-diethylaminoethoxy)ethyl ester
Formula : C20H31NO3 · C6H8O7
Molecular Weight : 525,59 g/mol
Component Concentration
Diethyl[2-[2-[(1-phenylcyclopentyl)formyloxy]ethoxy]ethyl]ammonium dihydrogen 2-
hydroxypropane-1,2,3-tricarboxylate
CAS-No. 23142-01-0 -
EC-No. 245-449-5

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Section 4. FIRST AID MEASURES
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
Indication of any immediate medical attention and special treatment needed
no data available

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Section 5. FIREFIGHTING MEASURES
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx)
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.Normal measures for preventive fire
protection.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Specific end uses
no data available

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Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested
and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and no data available
boiling range
g) Flash point no data available
h) Evaporation rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- no data available
octanol/water
p) Autoignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

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Section 10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
no data available
Hazardous decomposition products
Other decomposition products - no data available

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Section 11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
LD50 Oral - rat - 810 mg/kg
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
Inhalation - May cause respiratory irritation.
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation Harmful if inhaled. Causes respiratory tract irritation.
Ingestion Harmful if swallowed.
Skin Harmful if absorbed through skin. Causes skin irritation.
Eyes Causes serious eye irritation.
Additional Information
RTECS: GY3500000

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Section 12. ECOLOGICAL INFORMATION
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
no data available
Other adverse effects
no data available

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Section 13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed
professional waste disposal service to dispose of this material. Dissolve or mix the material with a
combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

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Section 14. TRANSPORT INFORMATION
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

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SECTION 15 - REGULATORY INFORMATION
N/A

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Pentoxyverine Citrate（Carbetapentane）是一种止咳药，常用于治疗与感冒等普通上呼吸道感染相关的咳嗽。

靶点

Target	Value
mAChR

体外研究

Pentoxyverine Citrate 具有类似阿托品的和局部麻醉的作用，并能有效抑制由普通上呼吸道感染引起的急性咳嗽。该药物通过抑制中枢神经系统的咳嗽反射来发挥止咳作用，尽管其确切的作用机制尚不完全清楚。作为一种毒蕈碱受体（M1亚型）拮抗剂和σ受体（σ1型）激动剂，Pentoxyverine Citrate 的抗胆碱能作用理论上能够放松肺泡，并减少痰的产生。

反应信息

• 作为反应物：
  描述：

  托可拉斯 、 溴酚蓝 以 氯仿 、 环己烷 为溶剂， 生成
  参考文献：
  名称：

  戊氧维林柠檬酸盐离子对与磺酞染料的光谱、热重研究和 DFT 计算

  摘要：

  摘要 柠檬酸戊氧维林 (PEN-citrate) 离子对与六种磺酞酸性染料；已制备溴甲酚绿（BCG）、溴酚蓝（BPB）、溴百里酚蓝（BTB）、溴甲酚紫（BCP）、溴氯酚蓝（BChPB）和溴二甲酚蓝（BXB）。应用紫外-可见光谱、傅里叶变换红外吸收光谱 (FTIR)、核磁共振 (1H NMR) 和质谱对这些离子对进行了结构表征和阐明。此外，光谱特性；计算了离子对的振子强度、跃迁偶极矩、跃迁能和共振能。借助热重分析对制备的化合物进行进一步表征，以确定它们的热稳定性。用于降解制备的离子对的活化能 (Ea) 及其一些热力学性质，例如使用 Horowitz-Metzger 的每个分解步骤的活化焓 ( ΔH )、活化熵 ( ΔS ) 和活化自由能 ( ΔG )方法进行了计算。通过执行量子化学计算，已在分子水平上探索了代表性离子对的结合性质。在这里，已经对 PEN、中性和带电（特别是阴离子）形式的溴酚蓝（BPB

  DOI：

  10.1016/j.molstruc.2020.128074
• 作为产物：
  描述：

  1-苯基环戊烷羧酸 在 4-二甲氨基吡啶 、 三光气 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 11.0h， 生成 托可拉斯
  参考文献：
  名称：

  一种枸橼酸喷托维林的制备方法

  摘要：

  本发明公开了一种枸橼酸喷托维林的制备方法，包括以下步骤：1)以甲苯作为反应溶剂，以DMAP作为催化剂，1‑苯基环戊基甲酸与三氯甲基碳酸酯，在甲苯回流温度下进行酰化反应，得到1‑苯基环戊基甲酰氯；2)将2‑(2‑二乙氨基乙氧基)乙醇加入步骤1)的溶液中进行缩合反应，得到喷托维林盐酸盐，再经碱处理，得到喷托维林游离碱的浓缩液；3)将步骤2)所得的喷托维林浓缩液溶解在丙酮溶液中，加入无水柠檬酸进行成盐反应，得到枸橼酸喷托维林。本发明的枸橼酸喷托维林的制备方法，其产品质量好、收率高、原料易得、成本低，具有较高经济效益；且易操作、反应条件温和、副反应少、环境污染小，适合工业化生产。

  公开号：

  CN117623949A

文献信息

• Substituted 1,3-thiazole compounds, their production and use
  申请人：——

  公开号：US20040053973A1

  公开（公告）日：2004-03-18

  (1) A 1,3-thiazole compound of which the 5-position is substituted with a 4-pyridyl group having a substituent including no aromatic group or (2) a 1,3-thiazole compound of which the 5-position is substituted with a pyridyl group having at the position adjacent to a nitrogen atom of the pyridyl group a substituent including no aromatic group has an excellent p38 MAP kinase inhibitory activity.

  (1) 一种1,3-噻唑化合物，其5位被取代为含有一个取代基的4-吡啶基团，该取代基不包括芳香基，或者(2) 一种1,3-噻唑化合物，其5位被取代为一个吡啶基团，该吡啶基团的氮原子邻近位置有一个取代基，该取代基不包括芳香基，具有出色的p38 MAP激酶抑制活性。
• BENZAZEPINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1422228A1

  公开（公告）日：2004-05-26

  The present invention provides a novel benzazepine derivative represented by formula : wherein, R1 is a 5- or 6-membered aromatic ring, R2 is lower alkyl group, etc., Y is an optionally substituted imino group, ring A and ring B are independently an optionally substituted aromatic ring, W is formula -W1-X2-W2- (W1 and W2 are independently S(O)m1 (m1 is 0, 1 or 2), etc., and X2 is an optionally substituted alkylene groupetc. ), a preparation method and use thereof.

  本发明提供了一种新型的苯并氮杂环衍生物，其由以下公式表示： 其中，R1是一个5-或6-成员的芳香环，R2是低级烷基团等，Y是可选地取代的亚氨基，环A和环B是独立地选自一个可选地取代的芳香环，W是公式-W1-X2-W2-（W1和W2是独立地为S(O)m1（m1是0、1或2）等，X2是一个可选地取代的亚烷基团等），其制备方法及其用途。
• [EN] HETEROCYCLIC COMPOUNDS AND THEIR USE AS RETINOID-RELATED ORPHAN RECEPTOR (ROR) GAMMA-T INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION EN TANT QU'INHIBITEURS GAMMA-T DU RÉCEPTEUR ORPHELIN APPARENTÉ AUX RÉCEPTEURS DES RÉTINOÏDES (ROR) )
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2016002968A1

  公开（公告）日：2016-01-07

  Provided are heterocyclic compounds having a RORγt inhibitory action represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  提供的是具有RORγt抑制作用的杂环化合物，其由公式(I)表示：其中每个符号如说明书中定义，或其盐。
• MEDICINAL COMPOSITIONS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1402900A1

  公开（公告）日：2004-03-31

  The present invention relates to an agent for the prophylaxis or treatment of pain, an agent for suppressing activation of osteoclast, and an inhibitor of osteoclast formation, which contains a p38 MAP kinase inhibitor and/or a TNF-α production inhibitor.

  本发明涉及一种用于预防或治疗疼痛的药剂，一种用于抑制破骨细胞活化的药剂，以及一种包含p38 MAP激酶抑制剂和/或TNF-α产生抑制剂的破骨细胞形成抑制剂。
• CONCOMITANT DRUGS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1354603A1

  公开（公告）日：2003-10-22

  The present invention relates to a pharmaceutical agent containing one or more kinds of a p38 MAP kinase inhibitor and/or a TNF-α production inhibitor and one or more kinds of drugs selected from the group consisting of (1) a non-steroidal antiinflammatory drug, (2) a disease-modifying anti-rheumatic drug, (3) an anti-cytokine drug, (4) an immunomodulator, (5) a steroid and (6) a c-Jun N-terminal kinase inhibitor in combination. This combination agent is useful as a prophylactic or therapeutic agent of the diseases such as rheumatism, arthritis and the like, and other diseases.

  本发明涉及一种含有一种或多种p38 MAP激酶抑制剂和/或TNF-α产生抑制剂以及从（1）非甾体抗炎药、（2）疾病修饰性抗风湿药、（3）抗细胞因子药物、（4）免疫调节剂、（5）类固醇和（6）c-Jun N末端激酶抑制剂中选择的一种或多种药物的药物制剂。这种组合药剂可用作预防或治疗风湿病、关节炎等疾病以及其他疾病的药物。