吉非罗齐杂质A | 637-32-1

• 物质功能分类: 原料药 - 抗寄生虫病药 - 抗疟药
• 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: 吉非罗齐杂质A
• 中文别名: 盐酸氯胍
• 英文名称: proguanil hydrochloride
• 英文别名: 1-(4-chlorophenyl)-5-isopropylbiguanide hydrochloride；N1-isopropyl-N5-(4-chloro)phenyl biguanide hydrochloride；1-(p-chlorophenyl)-5-isopropylbiguanide hydrochloride；N1-p-chlorophenyl-N5-isopropylbiguanide hydrochloride；chloroguanide hydrochloride；1-[Amino-(4-chloroanilino)methylidene]-2-propan-2-ylguanidine;hydron;chloride
• CAS: 637-32-1
• 化学式: C₁₁H₁₆ClN₅*ClH
• 分子量: 290.195
• InChiKey: SARMGXPVOFNNNG-UHFFFAOYSA-N

物化性质

• 熔点：
  249-2510C
• 溶解度：
  乙腈：水：~1mg/mL(60/40)
• 碰撞截面：
  161 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)：
  2.21
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  88.8
• 氢给体数：
  4
• 氢受体数：
  1

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  T
• 安全说明：
  S45
• 危险类别码：
  R25
• WGK Germany：
  3
• 海关编码：
  2925294500
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险标志：
  GHS06
• 危险品运输编号：
  UN 3249
• 危险性描述：
  H301
• 危险性防范说明：
  P301 + P310 + P330
• 储存条件：
  -20°C freezer

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Proguanil Hydrochloride
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. : 637-32-1
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
Acute toxicity, Oral (Category 3), H301
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
T Toxic R25
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
Pictogram
Signal word Danger
Hazard statement(s)
H301 Toxic if swallowed.
Precautionary statement(s)
P301 + P310 IF SWALLOWED: Immediately call a POISON CENTER or doctor/
physician.
Supplemental Hazard none
Statements
Other hazards - none

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SECTION 3: Composition/information on ingredients
Substances
Synonyms : Chlorguanide hydrochloride
N-(4-Chlorophenyl)-N'-(1-methylethyl)imidodicarbonimidic diamide
hydrochloride
Formula : C11H16ClN5.HCl
Molecular Weight : 290,19 g/mol
CAS-No. : 637-32-1
EC-No. : 211-283-7
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
PROGUANIL HYDROCHLORIDE
Acute Tox. 3; H301 -
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
PROGUANIL HYDROCHLORIDE
T, R25 -
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

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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. Take victim immediately to hospital. Consult a physician.
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. Consult a physician.
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
Carbon oxides, nitrogen oxides (NOx), Hydrogen chloride gas
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
Wear respiratory protection. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Prevent further leakage or spillage if safe to do so. 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.
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
Store with desiccant.
Specific end use(s)
A part 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
Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling
the product.
Personal protective equipment
Eye/face protection
Face shield and safety glasses 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
Where risk assessment shows air-purifying respirators are appropriate use a full-face particle
respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering
controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use
respirators and components tested and approved under appropriate government standards such
as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. 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- log Pow: 2,270
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
no data available
Hazardous decomposition products
Other decomposition products - no data available
In the event of fire: see section 5

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SECTION 11: Toxicological information
Information on toxicological effects
Acute toxicity
LD50 Oral - rat - 58 mg/kg
LD50 Oral - mouse - 27 mg/kg
LD50 Oral - rabbit - 150 mg/kg
LD50 Intravenous - rat - 33 mg/kg
Remarks: Behavioral:Altered sleep time (including change in righting reflex). Behavioral:Convulsions or
effect on seizure threshold.
LD50 Intravenous - mouse - 23 mg/kg
Remarks: Behavioral:Altered sleep time (including change in righting reflex). Behavioral:Convulsions or
effect on seizure threshold.
LD50 Subcutaneous - mouse - 35 mg/kg
LD50 Intravenous - rabbit - 44,85 mg/kg
Remarks: Behavioral:Altered sleep time (including change in righting reflex).
LD50 Intraperitoneal - guinea pig - 15 mg/kg
LD50 Intravenous - guinea pig - 39,51 mg/kg
Remarks: Behavioral:Altered sleep time (including change in righting reflex). Behavioral:Convulsions or
effect on seizure threshold.
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitisation
no data available
Germ cell mutagenicity
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
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: DU1750000
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

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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
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
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: 2811 IMDG: 2811 IATA: 2811
UN proper shipping name
ADR/RID: TOXIC SOLID, ORGANIC, N.O.S.
IMDG: TOXIC SOLID, ORGANIC, N.O.S. (PROGUANIL HYDROCHLORIDE)
IATA: Toxic solid, organic, n.o.s. (PROGUANIL HYDROCHLORIDE)
Transport hazard class(es)
ADR/RID: 6.1 IMDG: 6.1 IATA: 6.1
Packaging group
ADR/RID: III IMDG: III IATA: III
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

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SECTION 16: Other information
Full text of H-Statements referred to under sections 2 and 3.
Acute Tox. Acute toxicity
H301 Toxic if swallowed.
Full text of R-phrases referred to under sections 2 and 3
T Toxic
R25 Toxic if swallowed.
Further information
Copyright 2013 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

生物活性

Proguanil hydrochloride 是一种抗疟前药，被代谢为活性代谢物环鸟苷 (HY-12784)。它是一种二氢叶酸还原酶 (DHFR) 抑制剂。

体外研究

proguanil 本身在体外对疟疾的抑制作用较弱（IC50 = 2.4-19 μM），其效果依赖于活性代谢物环己基甘氨酸（Cycloguanil，IC50 = 0.5-2.5 nM）。Cycloguanil 同样是一种 DHFR 抑制剂。Atovaquone 和 Proguanil 的联合使用在体外表现出协同效应。这两种药物也对疟疾寄生虫的配子体和前红细胞（肝期）阶段有活性。

Proguanil 通过作为二胍类物质来增强 Atovaquone 的效果，而不是通过其代谢物 Cycloguanil (一种 DHFR 抑制剂)。这种增强作用仅针对 Atovaquone；其他线粒体电子传递抑制剂如 Myxothiazole 和 Antimycin 在 Proguanil 存在时不会产生类似效应。此外，Proguanil、其代谢物 4-氯苯基-1-二胍（CPB）和活性代谢物 Cycloguanil (CG) 能够可逆地抑制 5-HT3 受体响应，IC50 分别为 1.81、1.48 和 4.36 μM。

体内研究

Proguanil（口服；每公斤体重 2.9 mg；连续五天和六周）在 Wistar 阿拉伯大鼠中表现出五天的轻微退化变化，而六周后则表现为严重的退化变化。proguanil 治疗组的大鼠血清睾酮水平显著降低。

Malarone（Atovaquone 和 Proguanil 的联合使用）对实验性感染 B. gibsoni 的两只狗在慢性阶段和三只狗在急性阶段的治疗，结果显示寄生虫数量减少，并观察到临床改善。

反应信息

• 作为反应物：
  描述：

  吉非罗齐杂质A 在 氢氧化钾 、 溴 作用下， 以 甲醇 为溶剂， 以4%的产率得到(E)-3-[(4-chlorophenyl)imino]-N-isopropyl-3H-1,2,4-triazol-5-amine
  参考文献：
  名称：

  Goerlitzer; Huth; Jones, Pharmazie, 2005, vol. 60, # 4, p. 269 - 272

  摘要：

  DOI：
• 作为产物：
  描述：

  p-Chlorophenyl cyanoguanidine 、 异丙胺 、 氨 、 disodium;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxylatomethyl)amino]acetate 在 Copper sulfate pentahydrate p-Chlorophenyl cyanoguanidine 、 乙二胺四乙酸 、 水 作用下， 以 水 为溶剂， 反应 10.5h， 生成 吉非罗齐杂质A
  参考文献：
  名称：

  Process of Preparation of Proguanil

  摘要：

  本文揭示了1-(4-氯苯基)-5-异丙基双胍盐酸盐(盐酸普罗硅嗪)，公式-I，一种抗疟疾药物的制备过程。

  公开号：

  US20110263901A1
• 作为试剂：
  描述：

  p-Chlorophenyl cyanoguanidine 、 异丙胺 、 盐酸 、 乙二胺四乙酸 在 Copper sulfate pentahydrate 吉非罗齐杂质A 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 生成 吉非罗齐杂质A
  参考文献：
  名称：

  Process of Preparation of Proguanil

  摘要：

  本文揭示了1-(4-氯苯基)-5-异丙基双胍盐酸盐(盐酸普罗硅嗪)，公式-I，一种抗疟疾药物的制备过程。

  公开号：

  US20110263901A1

文献信息

• NAPHTHALENE-BASED INHIBITORS OF ANTI-APOPTOTIC PROTEINS
  申请人：Pellecchia Maurizio

  公开号：US20090105319A1

  公开（公告）日：2009-04-23

  Methods of using apogossypol and its derivatives for treating inflammation is disclosed. Also, there is described a group of compounds having structure A, or a pharmaceutically acceptable salt, hydrate, N-oxide, or solvate thereof are provided: wherein each R is independently selected from the group consisting of H, C(O)X, C(O)NHX, NH(CO)X, SO 2 NHX, and NHSO 2 X, wherein X is selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, an alkylaryl, and a heterocycle. Compounds of group A may be used for treating various diseases or disorders, such as cancer.

  使用阿波戈司宝及其衍生物治疗炎症的方法被披露。此外，还描述了一组具有结构A的化合物，或其药学上可接受的盐、水合物、N-氧化物或溶剂化合物： 其中每个R独立地选自H、C(O)X、C(O)NHX、NH(CO)X、SO2NHX和NHSO2X组成的组，其中X选自烷基、取代烷基、芳基、取代芳基、烷基芳基和杂环的组。A组化合物可用于治疗各种疾病或疾病，如癌症。
• CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY
  申请人：Cerulean Pharma Inc.

  公开号：US20130196906A1

  公开（公告）日：2013-08-01

  Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

  提供了关于使用CDP-治疗剂偶联物治疗疾病或紊乱的方法，例如自身免疫疾病、炎症性疾病、中枢神经系统紊乱、心血管疾病或代谢紊乱。还提供了CDP-治疗剂偶联物、包含CDP-治疗剂偶联物的颗粒以及包含CDP-治疗剂偶联物的组合物。
• Methods for treating an inflammatory condition or inhibiting JNK
  申请人：——

  公开号：US20040127536A1

  公开（公告）日：2004-07-01

  This invention is generally directed to Indazole Derivatives having the following structure: 1 or pharmaceutically acceptable salt thereof, wherein R 1 , R 2 and A are as defined herein. Such compounds have utility in the treatment of a wide range of diseases and disorders that are responsive to JNK inhibition, such as an inflammatory disease or disorder. Thus, methods of treating such diseases and disorders are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

  这项发明通常涉及吲唑衍生物，具有以下结构： 1 或药用可接受的盐，其中R 1 ，R 2 和A如本文所述定义。这类化合物在治疗对JNK抑制剂有响应的广泛疾病和障碍，如炎症性疾病或障碍中具有用途。因此，还披露了治疗这些疾病和障碍的方法，以及包含一个或多个上述化合物的药物组合物。
• Indazole compounds, compositions thereof and methods of treatment therewith
  申请人：Bhagwat S. Shripad

  公开号：US20050009876A1

  公开（公告）日：2005-01-13

  This invention is generally directed to the use of Indazole Compounds for treating or preventing diseases associated with protein kinases, including tyrosine kinases, such as proliferative diseases, inflammatory diseases, abnormal angiogenesis and diseases related thereto, atherosclerosis, macular degeneration, diabetes, obesity, pain and others. The methods comprise the administration to a patient in need thereof of an effective amount of an indazole compound that inhibits, modulates or regulates tyrosine kinase signal transduction. Novel indazole compounds or pharmaceutically acceptable salt thereof are presented herein.

  这项发明通常涉及使用吲唑化合物来治疗或预防与蛋白激酶相关的疾病，包括酪氨酸激酶，诸如增殖性疾病、炎症性疾病、异常血管生成及其相关疾病、动脉硬化、黄斑变性、糖尿病、肥胖、疼痛等。这些方法包括向有需要的患者施用有效量的吲唑化合物，以抑制、调节或控制酪氨酸激酶信号转导。本文中提供了一种新型的吲唑化合物或其药用可接受的盐。
• [EN] HETEROCYCLIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEURS UTILISATIONS
  申请人：INFINITY PHARMACEUTICALS INC

  公开号：WO2015051241A1

  公开（公告）日：2015-04-09

  Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

  本发明描述了调节激酶活性的化合物和药物组合物，包括PI3激酶活性，以及用于治疗与激酶活性相关的疾病和状况的化合物、药物组合物和方法，包括PI3激酶活性。