喹普利拉 | 82768-85-2

• 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: 喹普利拉
• 英文名称: quinaprilate
• 英文别名: Quinaprilat；[3S-[2[R*(R*)],3R*]]-2[2-[[1-(carboxy)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid；quinapril；quinapril diacid；{3S-[2(R*(R*))],3R*}-2-{2-[(1-carboxy-3-phenylpropyl)amino]-1-oxopropyl}-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid；(3S)-2-[(2S)-2-[[(1S)-1-carboxy-3-phenylpropyl]amino]propanoyl]-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
• CAS: 82768-85-2
• 化学式: C₂₃H₂₆N₂O₅
• 分子量: 410.47
• InChiKey: FLSLEGPOVLMJMN-YSSFQJQWSA-N

物化性质

• 熔点：
  166-1680C
• 比旋光度：
  D23 +20.9° (c = 1 in methanol)
• 沸点：
  674.5±55.0 °C(Predicted)
• 密度：
  1.289±0.06 g/cm3(Predicted)
• 溶解度：
  在DMSO中的溶解度≥23mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• WGK Germany：
  3

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Quinaprilat hydrate
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, Oral (Category 3)
Acute aquatic toxicity (Category 1)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Toxic if swallowed. Very toxic to aquatic organisms.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Danger
Hazard statement(s)
H301 Toxic if swallowed.
H400 Very toxic to aquatic life.
Precautionary statement(s)
P273 Avoid release to the environment.
P301 + P310 IF SWALLOWED: Immediately call a POISON CENTER or doctor/
physician.
Supplemental Hazard none
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R25 Toxic if swallowed.
R50 Very toxic to aquatic organisms.
S-phrase(s)
S45 In case of accident or if you feel unwell, seek medical advice immediately
(show the label where possible).
S61 Avoid release to the environment. Refer to special instructions/ Safety
data sheets.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : (3S)-2-[(2S)-2-[[(1S)-1-Carboxy-3-phenylpropyl]amino]-1-oxopropyl]-
1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid hydrate
Formula : C23H26N2O5 · xH2O
Molecular Weight : 410,46 g/mol
Component Concentration
(3S)-2-[(2S)-2-[[(1S)-1-Carboxy-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-
isoquinolinecarboxylic acid hydrate
-

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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
Lowered blood pressure, To the best of our knowledge, the chemical, physical, and toxicological properties
have not been thoroughly investigated.
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
Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate
ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
Environmental precautions
Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the
environment must be avoided.
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.
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 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
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).

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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- log Pow: 2,152
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
Strong oxidizing agents
Hazardous decomposition products

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Section 11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
no data available
LD50 Intravenous - rat - > 400 mg/kg
LD50 Intravenous - mouse - > 1.000 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
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion Toxic if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes May cause eye irritation.
Signs and Symptoms of Exposure
Lowered blood pressure, To the best of our knowledge, the chemical, physical, and toxicological properties
have not been thoroughly investigated.
Additional Information
RTECS: Not available

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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
Very toxic to aquatic life.

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Section 13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. 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. ((3S)-2-[(2S)-2-[[(1S)-1-Carboxy-3-phenylpropyl]amino]-1-
oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid hydrate)
IMDG: TOXIC SOLID, ORGANIC, N.O.S. ((3S)-2-[(2S)-2-[[(1S)-1-Carboxy-3-phenylpropyl]amino]-1-
oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid hydrate)
IATA: Toxic solid, organic, n.o.s. ((3S)-2-[(2S)-2-[[(1S)-1-Carboxy-3-phenylpropyl]amino]-1-
oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid hydrate)
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
no data available

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Section 16. OTHER INFORMATION
Further information
Copyright 2011 Co. 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. Co., shall not be held liable for any damage
resulting from handling or from contact with the above product. See reverse side of invoice or packing
slip for additional terms and conditions of sale.

制备方法与用途

奎那普利是一种口服活性非巯基血管紧张素转换酶(ACE)抑制剂，它是奎那普利的活性代谢物。奎那普利能够特异性地阻断血管紧张素I向血管收缩剂血管紧张素II的转化，并抑制缓激肽的降解。作为一种抗高血压药和血管扩张剂，奎那普利具有重要作用。

反应信息

• 作为反应物：
  描述：

  喹普利拉 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以50%的产率得到<3S-<2(R*),3α,11aβ>>-1,3,4,6,11,11a-hexahydro-3-methyl-1,4-dioxo-α-(2-phenylethyl)-2H-pyrazino<1,2-b>isoquinoline-2-acetic acid
  参考文献：
  名称：

  新型血管紧张素转化酶抑制剂奎纳普利及其相关化合物的合成。非巯基和巯基类型的结构活性关系存在差异。

  摘要：

  据报道奎纳普利（CI-906，22），其活性二酸（CI-928，33）和其二甲氧基类似物（CI-925，25）的合成和血管紧张素转化酶（ACE）抑制活性。这些四氢-3-异喹啉羧酸衍生物具有与依那普利相当的体外效能和体内功效。具有相同结构变化的巯基类似物也非常有效。相反，四氢-1-异喹啉羧酸和同源异吲哚啉-1-羧酸类似物在两种类型的效力上显示出惊人的差异，巯基类似物基本上是无活性的，而非巯基类似物与脯氨酸原型是等效的。这是第一个证据表明小分子ACE抑制剂的两个主要结构类别可能存在其他结合模式。

  DOI：

  10.1021/jm00160a026
• 作为产物：
  描述：

  喹那昔利 在 盐酸 、 sodium hydroxide 、 水 作用下， 以 甲醇 为溶剂， 生成 喹普利拉
  参考文献：
  名称：

  新型血管紧张素转化酶抑制剂奎纳普利及其相关化合物的合成。非巯基和巯基类型的结构活性关系存在差异。

  摘要：

  据报道奎纳普利（CI-906，22），其活性二酸（CI-928，33）和其二甲氧基类似物（CI-925，25）的合成和血管紧张素转化酶（ACE）抑制活性。这些四氢-3-异喹啉羧酸衍生物具有与依那普利相当的体外效能和体内功效。具有相同结构变化的巯基类似物也非常有效。相反，四氢-1-异喹啉羧酸和同源异吲哚啉-1-羧酸类似物在两种类型的效力上显示出惊人的差异，巯基类似物基本上是无活性的，而非巯基类似物与脯氨酸原型是等效的。这是第一个证据表明小分子ACE抑制剂的两个主要结构类别可能存在其他结合模式。

  DOI：

  10.1021/jm00160a026

文献信息

• [EN] NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL ANTI-DIABETIC AGENTS<br/>[FR] NOUVEAUX AGENTS ANTIDIABÉTIQUES UTILES AVEC DES DÉRIVÉS DE BENZIMIDAZOLE CYCLIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2010051176A1

  公开（公告）日：2010-05-06

  Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

  结构式（I）的新化合物是AMP-蛋白激酶的激活剂，可用于治疗、预防和抑制由AMPK激活的蛋白激酶介导的疾病。本发明的化合物对于治疗2型糖尿病、高血糖、代谢综合征、肥胖、高胆固醇血症和高血压是有用的。
• [EN] TRIAZOLE AGONISTS OF THE APJ RECEPTOR<br/>[FR] TRIAZOLES AGONISTES DU RÉCEPTEUR APJ
  申请人：AMGEN INC

  公开号：WO2016187308A1

  公开（公告）日：2016-11-24

  Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures where the definitions of the variables are provided herein.

  公式I和公式II的化合物，其药用盐，上述任何一种的立体异构体，或它们的混合物是APJ受体的激动剂，并可用于治疗心血管和其他疾病。公式I和公式II的化合物具有以下结构，其中变量的定义在此提供。
• [EN] TRIAZOLE PHENYL COMPOUNDS AS AGONISTS OF THE APJ RECEPTOR<br/>[FR] COMPOSÉS PHÉNYLE TRIAZOLE EN TANT QU'AGONISTES DU RÉCEPTEUR APJ
  申请人：AMGEN INC

  公开号：WO2018093579A1

  公开（公告）日：2018-05-24

  Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: (I), (II) where the definitions of the variables are provided herein.

  公式I和公式II的化合物，其药用盐，上述任何一个的立体异构体，或它们的混合物是APJ受体的激动剂，可能用于治疗心血管和其他疾病。公式I和公式II的化合物具有以下结构：(I)，(II)，其中变量的定义在此提供。
• [EN] TRIAZOLE FURAN COMPOUNDS AS AGONISTS OF THE APJ RECEPTOR<br/>[FR] COMPOSÉS DE TRIAZOLE FURANE UTILISÉS EN TANT QU'AGONISTES DU RÉCEPTEUR APJ
  申请人：AMGEN INC

  公开号：WO2018097944A1

  公开（公告）日：2018-05-31

  Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula (I) and Formula (II) have the following structures: (I); (II). Intermediates (V) are also claimed.

  式(I)和式(II)的化合物，其药用盐，任何上述化合物的立体异构体，或它们的混合物是APJ受体的激动剂，并且在治疗心血管和其他疾病方面有用。式(I)和式(II)的化合物具有以下结构：(I); (II)。中间体(V)也被要求。
• DIARYLMETHYLAMIDE DERIVATIVE HAVING ANTAGONISTIC ACTIVITY ON MELANIN-CONCENTRATING HORMONE RECEPTOR
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：EP2272841A1

  公开（公告）日：2011-01-12

  [Problem] To provide a melanin-concentrating hormone receptor antagonist useful as a pharmaceutical agent for central diseases, circulatory diseases, and metabolic diseases. [Means for Resolution] Provided is a diarylmethylamide derivative represented by formula (I): Wherein R1a, R1b, R2a, R2b, R3a, and R3b independently represent a hydrogen atom or the like, R4 represents a hydrogen atom, C1-6 alkyl, or the like, R5 represents a hydrogen atom or the like, Z represents C1-6 alkyl or the like, or R4 and Z together form a 4- to 6-membered nitrogen-containing hetero ring, Y1 represents H or the like, Y2 represents H, or Y1 and Y2 together form - O-CH2-, W represents C, SO, or the like, Ar1 represents 6-membered aryl or the like, Ar2 represents 6-membered aryl or the like, and ring A represents a benzene ring, a pyridine ring, or the like.

  [问题] 提供一种对黑色素浓缩激素受体拮抗剂，用作中枢疾病、循环疾病和代谢疾病的药用制剂。 [解决方法] 提供一种由式(I)表示的二芳基甲酰胺衍生物： 其中R1a、R1b、R2a、R2b、R3a和R3b独立地表示氢原子或类似物，R4表示氢原子、C1-6烷基或类似物，R5表示氢原子或类似物，Z表示C1-6烷基或类似物，或者R4和Z一起形成一个含氮杂环的4-至6-成员环，Y1表示H或类似物，Y2表示H，或者Y1和Y2一起形成-O-CH2-，W表示C、SO或类似物，Ar1表示6-成员芳基或类似物，Ar2表示6-成员芳基或类似物，环A表示苯环、吡啶环或类似物。