硫酸氯吡格雷 | 120202-66-6

• 物质功能分类: 生物化工 - 抑制剂 - 神经信号通路(Neuronal Signaling)
• 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: 硫酸氯吡格雷
• 中文别名: 硫酸氢氯吡格雷；(S)-(+)-2-(2-氯苯基)-2-(6,7-二氢噻吩并[3,2-C]吡啶-5-基)乙酸甲酯硫酸盐；硫酸氢氯吡格雷II型；(S)-(+)-氯吡格雷硫酸盐；(S)-(+)-(2-氯苯基)-6,7-二氢噻吩并[3,2-c]吡啶-5(4H)乙酸甲酯硫酸氢盐；氯吡格雷硫酸氢盐；氯吡格雷硫酸盐；硫酸氢氯吡格雷I；氯匹格雷硫酸盐；(2-氯苯基)-6,7-二氢噻吩并[3,2-C]吡啶-5-(4H)-乙酸甲酯硫酸盐；硫酸氯吡格雷(晶型2)；(+/-)-硫酸氢氯吡格雷；(S)-alpha-(2-氯苯基)-6,7-二氢噻吩并[3,2-c]吡啶-5(4H)乙酸甲酯硫酸氢盐；二硫酸氯吡格雷；二硫酸氯匹多瑞；硫酸氢氯吡格雷Ⅰ；硫酸氢氯吡格雷Ⅱ；硫酸氢氯吡格雷II
• 英文名称: (S)-(+)-clopidogrel bisulfate
• 英文别名: clopidogrel bisulfate；clopidogrel hydrogen sulfate；Clopidogrel sulfate；clopidogrel bisulphate；(S)-(+)-clopidogrel hydrogen sulfate；clopidogrel hydrogen sulphate；CLOPIDOGREL；hydrogen sulfate;methyl (2S)-2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-ium-5-yl)acetate
• CAS: 120202-66-6
• 化学式: C₁₆H₁₆ClNO₂S*H₂O₄S
• mdl: MFCD00876395
• 分子量: 419.907
• InChiKey: FDEODCTUSIWGLK-RSAXXLAASA-N

物化性质

• 熔点：
  174-176°C
• 溶解度：
  二甲基亚砜：~26 mg/mL
• 颜色/状态：
  Colorless oil
• 蒸汽压力：
  2.9X10-7 mm Hg at 25 °C (est)
• 旋光度：
  Specific optical rotation at 25 °C for D (sodium) line = +55.10 deg (c = 1.61 in methanol)
• 解离常数：
  pKa = 5.3 (tertiary amine) (est)
• 碰撞截面：
  167.7 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)：
  4.03
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.312
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  8

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用的总结：目前没有关于母乳喂养期间使用氯吡格雷的已发表信息。制造商报告，在母乳喂养期间使用氯吡格雷的少量上市后案例中，未观察到对哺乳婴儿的任何不良影响。由于目前没有关于母乳喂养期间使用氯吡格雷的已发表信息，可能更倾向于使用其他药物，特别是在哺乳新生儿或早产儿时。如果哺乳母亲使用，需监测婴儿是否有瘀伤和出血情况。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关的已发表信息。 ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关的已发表信息。

◉ Summary of Use during Lactation:No published information is available on the use of clopidogrel during breastfeeding. The manufacturer reports that no adverse effects have been observed in breastfed infants with maternal clopidogrel use during lactation in a small number of postmarketing cases. Since no published information is available on the use of clopidogrel during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. If it is used by a nursing mother, monitor the infant for bruising and bleeding. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

安全信息

• 危险等级：
  8
• 安全说明：
  S22,S24/25
• WGK Germany：
  3
• 海关编码：
  2942000000
• 危险品运输编号：
  UN 1759
• 危险类别：
  8
• 包装等级：
  II
• 危险性防范说明：
  P280
• 危险性描述：
  H302,H312,H332
• 储存条件：
  2-8°C

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Clopidogrel Bisulfate
REACH No. : A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
CAS-No. : 120202-66-6
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

---

SECTION 2: Hazards identification
Classification of the substance or mixture
Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008.
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
The product does not need to be labelled in accordance with EC directives or respective national laws.
Other hazards - none

---

SECTION 3: Composition/information on ingredients
Substances
Molecular Weight : 419,90 g/mol
CAS-No. : 120202-66-6
No components need to be disclosed according to the applicable regulations.

---

SECTION 4: First aid measures
Description of first aid measures
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration.
In case of skin contact
Wash off with soap and plenty of water.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water.
Most important symptoms and effects, both acute and delayed
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
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
no data available
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

---

SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Avoid dust formation. Avoid breathing vapours, mist or gas.
For personal protection see section 8.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
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
Provide appropriate exhaust ventilation at places where dust is formed.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: 2 - 8 °C
Specific end use(s)
Apart from the uses mentioned in section 1.2 no other specific uses are stipulated

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SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
General industrial hygiene practice.
Personal protective equipment
Eye/face protection
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
Choose body protection in relation to its type, to the concentration and amount of dangerous
substances, and to the specific work-place., The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Respiratory protection is not required. Where protection from nuisance levels of dusts are desired,
use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and
approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Do not let product enter drains.

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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) Evapouration 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) Auto-ignition 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
Stable under recommended storage conditions.
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents, Strong acids and strong bases
Hazardous decomposition products
Other decomposition products - no data available
In the event of fire: see section 5

---

SECTION 11: Toxicological information
Information on toxicological effects
Acute toxicity
no data available
no data available
Skin corrosion/irritation
no data available
no data available
Serious eye damage/eye irritation
no data available
no data available
Respiratory or skin sensitisation
no data available
no data available
Germ cell mutagenicity
no data available
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
no data available
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Additional Information
RTECS: Not available
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

---

SECTION 12: Ecological information
Toxicity
no data available
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
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
Other adverse effects
no data available
no data available

---

SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company.
Contaminated packaging
Dispose of as unused product.

---

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
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
no data available
Chemical Safety Assessment
For this product a chemical safety assessment was not carried out

---

SECTION 16: Other information
Further information
Copyright 2014 Co. LLC. License granted to make unlimited paper copies for internal use
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

制备方法与用途

氯吡格雷

简介 氯吡格雷是一种抗血小板药物，广泛用于治疗心肌梗死、缺血性脑卒中和周围动脉缺血等疾病。合理使用可以有效预防动脉粥样硬化血栓事件的发生；反之，则可能引发严重不良后果。

临床应用 硫酸氯吡格雷用于预防和治疗由血小板高聚集引起的心脏、大脑及动脉循环障碍疾病，以及预防动脉粥样硬化血栓的形成。

不良反应 可能出现皮疹、腹泻、腹痛、消化不良、颅内出血、消化道出血，严重粒细胞减少。孕妇应避免使用此药物。

生物活性 氯吡格雷二盐酸盐（Clopidogrel Bisulfate, SR-25990C, Iscover, Plavix）是一种口服的噻吩吡啶类抗血小板药物。

靶点

Target	Value
P2Y12	-

体外研究 氯吡格雷通过细胞色素P450（CYP）酶转化为活性代谢物。它能够抑制RGM-1细胞中由EGF刺激的受体、PERK表达和细胞增殖，并在过表达表皮生长因子的RGM-1细胞中同样表现出这种作用，但效果较弱。此外，在接受牙周修复大鼠中，氯吡格雷可增加血管数量，减少中性核数及依附和骨质流失；与生理盐水处理相比，它还能降低CXCL4、CXCL12和PDGF含量，而不影响CXCL5。

体内研究 在大鼠的溃疡缘中，氯吡格雷（每天2毫克和10毫克/公斤）显著减少胃上皮细胞增殖及EGF受体和磷酸化细胞外信号调节激酶（PERK）的表达。在充血性心脏衰竭的大鼠模型中，氯吡格雷改善了血管内皮功能和NO生物利用度，并增强了AKT和eNOS的磷酸化水平。在充血性心脏衰竭大鼠与阿司匹林联用的情况下，对兔耳横断诱导出血时间延长表现出叠加效应，这表明其具有环氧合酶和ADP的联合抑制作用，从而显著增强抗血栓效果。

用途

• 抗凝血药
• P2Y12受体抑制剂

反应信息

• 作为反应物：
  描述：

  硫酸氯吡格雷 在 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 以100 %的产率得到氯吡格雷
  参考文献：
  名称：

  药物分子的后期 C(sp3)–H 甲基化

  摘要：

  众所周知，甲基在药物分子中发挥着关键作用，尤其是那些带有饱和杂环核心的药物分子。因此，将甲基基团安装到复杂分子上的方法备受期待。后期C-H官能化是一种特别有吸引力的方法，它允许化学家绕过冗长的合成过程并促进药物类似物的快速合成。在此，我们公开了通过一系列饱和杂环的C( sp 3 )–H官能化直接引入甲基，这是通过十钨酸盐光催化和独特的镍介导的S H 2 键形成的合并实现的。为了进一步证明其作为后期功能化工具的合成实用性，该方法应用于一系列药物分子，以形成一系列甲基化药物类似物。

  DOI：

  10.1021/jacs.2c13396
• 作为产物：
  描述：

  氯吡格雷 在 硫酸 作用下， 以 水 、 丙酮 为溶剂， 反应 7.5h， 以75%的产率得到硫酸氯吡格雷
  参考文献：
  名称：

  氯吡格雷硫酸氢盐的不对称合成

  摘要：

  摘要 通过应用以[（1S）-1-（4-甲氧基苯基）乙基]胺盐酸盐为手性助剂的Strecker反应，开发了（S）-（+）-氯吡格雷硫酸氢盐的不对称合成。将2-氯苯甲醛加到氰化钠和[（1S）-1-（4-甲氧基苯基）乙基]胺盐酸盐的溶液中，得到非对映异构纯的（2S）-（2-氯苯基）{[（1S）-1 -（4-甲氧基苯基）乙基]氨基}乙腈盐酸盐。然后裂解手性助剂并伴随水解腈基团，得到对映体纯的（2S）-2-（2-氯苯基）甘氨酸盐酸盐，其为（S）-（+）-氯吡格雷的关键中间体。 通过应用以[（1S）-1-（4-甲氧基苯基）乙基]胺盐酸盐为手性助剂的Strecker反应，开发了（S）-（+）-氯吡格雷硫酸氢盐的不对称合成。将2-氯苯甲醛加到氰化钠和[（1S）-1-（4-甲氧基苯基）乙基]胺盐酸盐的溶液中，得到非对映异构纯的（2S）-（2-氯苯基）{[（1S）-1 -（4-甲氧基苯基）乙基]氨基}乙腈盐酸

  DOI：

  10.1055/s-0032-1316852
• 作为试剂：
  描述：

  硫酸 、 溶剂黄146 、 氯吡格雷 在 硫酸氯吡格雷 作用下， 以 甲基叔丁基醚 为溶剂， 反应 24.0h， 以is obtained (yield 84%)的产率得到硫酸氯吡格雷
  参考文献：
  名称：

  Process for Preparing Clopidogrel Bisulphate

  摘要：

  提供制备氯吡格雷双硫酸盐I型的过程。

  公开号：

  US20090247569A1

文献信息

• Prodrugs of anti-platelet agents
  申请人：Kandula Mahesh

  公开号：US09175008B1

  公开（公告）日：2015-11-03

  The invention relates to the compounds of formula I, formula II, formula Ia, formula IIb or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, formula II, formula Ia, formula IIb and methods for treating or preventing atherothrombosis may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment or management of ischemia, stroke, cerebral thrombosis, arterial thrombosis, thrombotic cerebrovascular, cardiovascular diseases and blood clots.

  该发明涉及公式I、公式II、公式Ia、公式IIb或其药用可接受盐，以及其多晶型、溶剂合物、对映体、立体异构体和水合物。包含公式I、公式II、公式Ia、公式IIb化合物的有效量的药物组合物，以及用于治疗或预防动脉血栓形成的方法可以制成口服、颊内、直肠、局部、经皮、经粘膜、静脉、肠道给药、糖浆或注射剂。这种组合物可用于治疗或管理缺血、中风、脑血栓形成、动脉血栓形成、血栓性脑血管疾病和血栓。
• FACTOR XIA-INHIBITING PYRIDOBENZAZEPINE AND PYRIDOBENZAZOCINE DERIVATIVES
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20170275282A1

  公开（公告）日：2017-09-28

  The invention relates to substituted pyridobenzazepine and pyridobenzazocine derivatives and to processes for preparation thereof, and also to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and oedemas, and also ophthalmic disorders.

  这项发明涉及取代的吡啶苯并脑和吡啶苯并哌啶衍生物，以及其制备方法，还涉及将其用于生产用于治疗和/或预防疾病的药物，特别是心血管疾病，最好是血栓性或血栓栓塞性疾病，水肿，以及眼科疾病。
• [EN] SUBSTITUTED OXOPYRIDINE DERIVATIVES<br/>[FR] DÉRIVÉS D'OXOPYRIDINE SUBSTITUÉS
  申请人：BAYER PHARMA AG

  公开号：WO2017005725A1

  公开（公告）日：2017-01-12

  The invention relates to substituted oxopyridine derivatives and to processes for their preparation, and also to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and o edemas, and also ophthalmic disorders.

  这项发明涉及替代氧吡啶衍生物及其制备方法，以及它们用于制备治疗和/或预防疾病的药物，特别是心血管疾病，最好是血栓性或血栓栓塞性疾病，以及水肿和眼科疾病。
• HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
  申请人：McCall John M.

  公开号：US20140128392A1

  公开（公告）日：2014-05-08

  Disclosed herein are new heterocyclic compounds of Formula IIa: and compositions thereof, and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.

  本文披露了新的Formula IIa的杂环化合物及其组合物，以及它们作为治疗疾病的药物的应用。还提供了在人类或动物主体中抑制PAS激酶（PASK）活性的方法，用于治疗糖尿病等疾病。
• [EN] IMIDAZOTHIADIAZOLE AND IMIDAZOPYRAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION<br/>[FR] DÉRIVÉS D'IMIDAZOTHIADIAZOLE ET D'IMIDAZOPYRAZINE UTILISÉS COMME INHIBITEURS DU RÉCEPTEUR 4 ACTIVÉ PAR UNE PROTÉASE (PAR4) POUR LE TRAITEMENT DE L'AGRÉGATION PLAQUETTAIRE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2013163279A1

  公开（公告）日：2013-10-31

  The present invention provides thiazole compounds of Formula I wherein W, Y, R0, R2, R4, R5, R6, R7, X1, X2, X3 and X4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

  本发明提供了式I的噻唑化合物，其中W、Y、R0、R2、R4、R5、R6、R7、X1、X2、X3和X4如本文所定义，或其立体异构体、互变异构体、药学上可接受的盐、前药酯或溶剂化合物形式，其中所有变量均如本文所定义。这些化合物是血小板聚集抑制剂，因此可用作治疗或预防血栓栓塞性疾病的药物。