75847-73-3

• 常用中文名：依那普利
• 常用英文名：Enalapril
• CAS号：75847-73-3
• 分子式：C₂₀H₂₈N₂O₅
• 分子量：376.447
• 相关类别： 原料药 循环系统用药 抗高血压病药
• 发布时间：2018-02-05 08:00:00
• 更新时间：2024-01-04 09:32:07
• Enalapril是血管紧张素转换酶(ACE)抑制剂。
• 用于治疗高血压，是ACE抑制剂。用于原发性、肾性高血压、肾血管性高血压、恶性高血压等，还适用于充血性心力衰竭，特别是高肾素、高血钙需要长期用药的高血压病人和洋地黄、利尿药治疗无效的充血性心力衰竭的患者，还可用于卡托普利不能耐受的病人。 本品是血管紧张素转换酶抑制药，口服后在肝脏内水解成依那普利拉而发挥作用。后者对血管紧张素转换酶的抑制作用为卡托普利的8倍以上。降压作用机制与卡托普利相同，但作用时间持久。本品降压同时能保持心肌收缩力，不影响心输出量。在充血性心力衰竭患者能使外周血管阻力和肺毛细血管楔嵌压降低，从而减轻心脏前、后负荷，改善心脏功能。本品能增加肾血流量，对血糖、尿酸和胆固醇代谢无明显影响。5 适应症状
  ①用于治疗高血压，可单独应用或与其他降压药如利尿药合用。
  ②用于治疗心力衰竭，可单独应用或与强心药利尿药合用。
  本品适用于各种程度高血压病、肾血管性高血压及糖尿病合并高血压病患者的治疗；
  也可用于慢性充血性心力衰竭的治疗，尤以常规应用洋地黄或利尿药难于控制者，能延缓充血性心力衰竭症状的临床进展及减少住院治疗的需要。
  由于本品效果优于卡托普利，不良反应又较轻，故使用日益广泛，为高血压治疗的首选药。

名称

• 中文名: 依那普利
• 英文名: enalapril
• 中文别名: (S)-1-(N-(1-(乙氧羰基)-3-苯丙基)-L-丙氨酰基)-L-脯氨酸
• 英文别名: Enacard; [3H]-Eletriptan; N-[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline; Eletriptan [INN:BAN]; Acesistem; Eletriptan; Lotrial; EINECS 278-375-7; Naprilene; (R)-5-(2-phenylsulphonylethyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole; L-Proline, N-((1S)-1-(ethoxycarbonyl)-3-phenylpropyl)-L-alanyl-; Enalapril; 1-[N-[(S)-1-Carboxy-3-phenylpropyl]-1-alanyl]-L-proline 1'-Ethyl Ester; enalaprila; MFCD00865774; N-{(1S)-1-[(ethyloxy)carbonyl]-3-phenylpropyl}-L-alanyl-L-proline; Reniten; N-[(2S)-1-Ethoxy-1-oxo-4-phenyl-2-butanyl]alanyl-L-proline; Eletriptan (INN); Enap; Renitec; N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]alanylproline; 3-(N-methyl-2(R)-pyrrolidinylmethyl)-5-(2-phenylsulphonylethyl)-1H-indole; Hipoartel; Amprace; Relpax; olivin; Xanef; N-[(2S)-1-Ethoxy-1-oxo-4-phenylbutan-2-yl]-L-alanyl-L-proline; eletriptanum; L-Proline, N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]alanyl-; Enapren; N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline; Enaloc; Renivace; Glioten; L-Proline, N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-; N-[(2S)-1-Ethoxy-1-oxo-4-phenyl-2-butanyl]-L-alanyl-L-proline; Pres; Innovace; (R)-3-((1-methylpyrrolidin-2-yl)methyl)-5-(2-(phenylsulfonyl)ethyl)-1H-indole

物化性质

• 密度: 1.2±0.1 g/cm3
• 沸点: 582.3±50.0 °C at 760 mmHg
• 熔点: 143-144.5ºC
• 分子式: C₂₀H₂₈N₂O₅
• 分子量: 376.447
• 闪点: 306.0±30.1 °C
• 精确质量: 376.199829
• PSA: 170.54000
• LogP: 2.43
• 蒸汽压: 0.0±1.7 mmHg at 25°C
• 折射率: 1.550
• 储存条件: 室温
• 分子结构:

  1、 摩尔折射率：99.53

  2、 摩尔体积（cm³/mol）：312.5

  3、 等张比容（90.2K）：836.4

  4、 表面张力（dyne/cm）：51.2

  5、 极化率（10-24cm3）：39.45

• 更多:

  1.性状：白色针状结晶或结晶性粉末

  2.熔点：143~144.5

  2.溶解性：易溶于水，微溶于乙腈

生物活性

• 描述: Enalapril是血管紧张素转换酶(ACE)抑制剂。
• 相关类别:
  信号通路 >> 代谢酶/蛋白酶 >> 血管紧张素转换酶(ACE)
  天然产物 >> 其他
  研究领域 >> 心血管疾病
• 参考文献:

  [1]. http://en.wikipedia.org/wiki/Enalapril

MSDS

Section1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE Product identifiers Product name: Enalapril : CDS020548 CAS-No.: 75847-73-3 Section2. HAZARDS IDENTIFICATION Classification of the substance or mixture Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP] Skin sensitization (Category 1) Reproductive toxicity (Category 2) Classification according to EU Directives 67/548/EEC or 1999/45/EC May cause sensitization by skin contact. Possible risk of impaired fertility. Possible risk of harm to the unborn child. Label elements Labelling according Regulation (EC) No 1272/2008 [CLP] Pictogram Signal wordWarning Hazard statement(s) May cause an allergic skin reaction. Suspected of damaging fertility or the unborn child. Precautionary statement(s) Wear protective gloves. Supplemental Hazardnone Statements According to European Directive 67/548/EEC as amended. Hazard symbol(s) R-phrase(s) R43May cause sensitization by skin contact. R62Possible risk of impaired fertility. R63Possible risk of harm to the unborn child. S-phrase(s) S22Do not breathe dust. S26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S36Wear suitable protective clothing. Other hazards - none Section3. COMPOSITION/INFORMATION ON INGREDIENTS Substances : (S)-(−)-1-[N-(1-Ethoxycarbonyl-3-phenylpropyl)-L-alanyl]-Lproline Synonyms Formula: C20H28N2O5 Molecular Weight: 376,45 g/mol ComponentConcentration (S)-(−)-1-[N-(1-Ethoxycarbonyl-3-phenylpropyl)-L-alanyl]-Lproline CAS-No.75847-73-3- Section4. 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 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 hematopoiesis, renal damage, varation of retinal blood vessels, pruritus, taste disturbance, Exerts a potent hypotensive action Indication of any immediate medical attention and special treatment needed no data available Section5. 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 Section6. 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 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. Section7. 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. Specific end use(s) no data available Section8. 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 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 N100 (US) or type P3 (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). Section9. PHYSICAL AND CHEMICAL PROPERTIES Information on basic physical and chemical properties a) AppearanceForm: solid b) Odourno data available c) Odour Thresholdno data available d) pHno data available e) Melting point/freezingno data available point f) Initial boiling point and no data available boiling range g) Flash pointnot applicable h) Evaporation rateno data available i) Flammability (solid, gas) no data available j) Upper/lowerno data available flammability or explosive limits k) Vapour pressureno data available l) Vapour densityno data available m) Relative densityno data available n) Water solubilityno data available o) Partition coefficient: n- no data available octanol/water p) Auto-ignitionno data available temperature q) Decompositionno data available temperature r) Viscosityno data available s) Explosive propertiesno data available t) Oxidizing propertiesno data available Other safety information no data available Section10. 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 Other decomposition products - no data available Section11. TOXICOLOGICAL INFORMATION Information on toxicological effects Acute toxicity LD50 Oral - rat - 2.973 mg/kg LD50 Oral - mouse - 3.507 mg/kg LD50 Subcutaneous - rat - 1.418 mg/kg LD50 Intravenous - rat - 849 mg/kg LD50 Intravenous - mouse - 859 mg/kg LD50 Subcutaneous - mouse - 1.160 mg/kg Skin corrosion/irritation no data available Serious eye damage/eye irritation no data available Respiratory or skin sensitization May cause sensitization by skin contact. 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 Suspected human reproductive toxicant 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 InhalationMay be harmful if inhaled. May cause respiratory tract irritation. IngestionMay be harmful if swallowed. SkinMay be harmful if absorbed through skin. May cause skin irritation. EyesMay cause eye irritation. Signs and Symptoms of Exposure hematopoiesis, renal damage, varation of retinal blood vessels, pruritus, taste disturbance, Exerts a potent hypotensive action Additional Information RTECS: TW3665500 Section12. 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 Section13. 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. Section14. 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: noIMDG Marine Pollutant: noIATA: no Special precautions for user no data available Section15. 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 SECTION 16 - ADDITIONAL INFORMATION N/A

安全

• 符号: GHS07, GHS08
• 信号词: Warning
• 危害声明: H317-H361
• 警示性声明: P280
• 危害码 (欧洲): Xi
• 安全声明 (欧洲): S22-S24/25
• 危险品运输编码: NONH for all modes of transport
• RTECS号: TW3665500

合成路线

上下游产品

上游产品  8
82717-96-2 147-85-3 13485-59-1 17451-20-6
120924-94-9 64920-29-2 108428-39-3 103377-40-8
下游产品  3
76095-16-4 76420-72-9 115729-52-7

制备

方法1：α-氧代苯丁酸乙酯和L-丙氨酰-L-脯氨酸二肽在4A分子筛作用下缩合，生成Schiff’s碱，再用氰硼氢化钠还原即得依那普利，如进一步和马来酸成盐可得马来酸依那普利。

方法2：也可用α-溴代苯丁酸乙酯和L-丙氨酰-L-脯氨酸二肽在二甲基甲酰胺溶液中，三乙胺作用下缩合，一步即可得到依那普利。

方法3：上述方法均需苯丁酸的衍生物，在原料受限制时可采用下面的方法。
用丁烯二酸酐对苯进行酰化，生成伊苯甲酰丙烯酸，收率90.1%。
β-苯甲酰丙烯酸、无水乙醇、苯和浓硫酸，回流分水。氢氧化钠溶液中和，饱和氯化钠和水洗，干燥，过滤。滤液减压浓缩，蒸馏收集148～150℃/133Pa的馏分，得β-苯甲酰丙烯酸乙酯，收率97.3%。
β-苯甲酰丙烯酸乙酯、丙氨酸苄酯对甲苯磺酸盐、无水乙醇和三乙胺混合，在室温下搅拌。过滤出固体，烘干得化合物(I)，收率75%。
化合物(I)、硫酸、冰乙酸和10%钯-炭催化剂，通氢。过滤，滤液减压浓缩至干，碱处理后洗涤。用乙酸乙酯重结晶，得化合物(Ⅱ)，收率52.6%。
化合物(Ⅱ)和N-羟基琥珀酰亚胺溶于二甲基甲酰胺，冰浴冷却下分批加入二环己基碳化二亚胺(DCC)，在室温下搅拌。冰浴冷却下加入L-脯氨酸四甲基铵盐的二甲基甲酰胺溶液，反应。滤去固体，用酸碱处理后，用乙酸乙酯提取。提取液干燥，减压浓缩。残液溶于乙腈，加入马来酸的乙腈溶液，充分搅拌后放置过夜。滤得固体，用乙腈重结晶，得白色针状结晶的马来酸依那普利，收率46.7%。

上面的化合物(11)直接和脯氨酸叔丁酯，在DCC存在下缩合，然后水解脱去叔丁醇得到依那普利。