82834-16-0

• 常用中文名：培哚普利
• 常用英文名：Perindopril
• CAS号：82834-16-0
• 分子式：C₁₉H₃₂N₂O₅
• 分子量：368.468
• 相关类别： 原料药 循环系统用药 抗高血压病药
• 发布时间：2018-04-05 08:00:00
• 更新时间：2024-01-02 11:10:47
• Perindopril是长效血管紧张素转换酶(ACE)抑制剂。

名称

• 中文名: 培哚普利
• 英文名: perindopril
• 中文别名: 培垛普利; 1-[2-[[(1S)-(1-乙氧羰基)丁基]氨基]丙酰]-(2S,3aS,7aS)-八氢吲哚-2-羧酸; [2S-[1-[R^^,(R^^)],2Α,3ΑΒ,7ΑΒ]]-1-[2-[[1-(乙氧羰基)丁基]氨基]-1-氧丙基]八氢-1H-吲哚-2-羧酸
• 英文别名: (2S,3aS,7aS)-1-[(2S)-2-{[(2S)-1-Ethoxy-1-oxo-2-pentanyl]amino}propanoyl]octahydro-1H-indole-2-carboxylic acid; (2S,3aS,7aS)-1-[(2S)-2-{[(2S)-1-Ethoxy-1-oxopentan-2-yl]amino}propanoyl]octahydro-1H-indole-2-carboxylic acid (non-preferred name); S-9490-3; Procaptan; MCNA-2833; Coversyl; (2S,3aS,7aS)-1-[(2S)-2-{[(1S)-1-(ethoxycarbonyl)butyl]amino}propanoyl]octahydro-1H-indole-2-carboxylic acid (non-preferred name); McN-A-2833-109; (2S,3aS,7aS)-1-[(S)-N-[(S)-1-Carboxybutyl]alanyl]hexahydro-2-indolinecarboxylic Acid 1-Ethyl Ester; (2S)-2-[(1S)-1-Carbethoxybutylamino]-1-oxopropyl-(2S,3aS,7aS)-perhydroindole-2-carboxylic Acid; [2S-[1-[R*,(R*)],2a,3ab,7ab]]-1-[2-[[1-(Ethoxycarbonyl)butyl]amino]-1-oxopropyl]octahydro-1H-indole-2-carboxylic Acid; Perindopril; S-9490; McN-A 2833; S-9490,McNA-2833; MFCD00865859

物化性质

• 密度: 1.1±0.1 g/cm3
• 沸点: 537.4±45.0 °C at 760 mmHg
• 熔点: 100-101°C
• 分子式: C₁₉H₃₂N₂O₅
• 分子量: 368.468
• 闪点: 278.8±28.7 °C
• 精确质量: 368.231110
• PSA: 95.94000
• LogP: 3.36
• 外观性状: 白色粉末
• 蒸汽压: 0.0±3.1 mmHg at 25°C
• 折射率: 1.512
• 储存条件: -20°C Freezer
• 分子结构:

  1、 摩尔折射率：96.17

  2、 摩尔体积（cm³/mol）：320.3

  3、 等张比容（90.2K）：829.3

  4、 表面张力（dyne/cm）：44.9

  5、 极化率（10-24cm3）：38.12

• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:2

  3.氢键受体数量:6

  4.可旋转化学键数量:9

  5.互变异构体数量:无

  6.拓扑分子极性表面积95.9

  7.重原子数量:26

  8.表面电荷:0

  9.复杂度:524

  10.同位素原子数量:0

  11.确定原子立构中心数量:5

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

• 更多:

  1.性状：结晶。

  2.熔点（ºC）：134。

生物活性

• 描述: Perindopril是长效血管紧张素转换酶(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 >> 生物碱
  研究领域 >> 心血管疾病
• 参考文献:

  [1]. Vaclavik J, Perindopril in the treatment of hypertension and cardiovascular diseases: evolution continues with the orodispersible dosage form. Vnitr Lek. 2013 Apr;59(4):290-4.

  [2]. Napalkov DA. Therapy with perindopril: organoprotection, not just the antihypertensive effect. Kardiologiia. 2012;52(12):80-3.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : NL5999400 CHEMICAL NAME : 11H-Indole-2-carboxylic acid, octahydro-1-(2-((1-ethoxycarbonyl)butyl)amino)-1-oxop ropyl)-, (2S-(1(R*(R*)),2-alpha,3a-beta,7a-beta))- CAS REGISTRY NUMBER : 82834-16-0 LAST UPDATED : 199612 DATA ITEMS CITED : 15 MOLECULAR FORMULA : C19-H32-N2-O5 MOLECULAR WEIGHT : 368.53 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 10,446,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 323 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 10,446,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >2500 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - respiratory depression REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22,1673,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 679 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 10,446,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >1600 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 10,446,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE/DURATION : >500 mg/kg TOXIC EFFECTS : Gastrointestinal - nausea or vomiting REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22,1679,1994 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 4102 mg/kg/78W-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - interstitial nephritis Kidney, Ureter, Bladder - changes in bladder weight REFERENCE : CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 10,446,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 365 mg/kg/52W-I TOXIC EFFECTS : Cardiac - changes in heart weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Metabolism (Intermediary) - lipids including transport REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22,1689,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 273 mg/kg/91D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - other changes in urine composition Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 10,446,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2184 mg/kg/26W-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - interstitial nephritis Kidney, Ureter, Bladder - changes in bladder weight REFERENCE : CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 10,446,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 4600 mg/kg/26W-I TOXIC EFFECTS : Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22,1711,1994 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 192 mg/kg SEX/DURATION : female 6-17 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22,1729,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 416 mg/kg SEX/DURATION : female 17-21 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Maternal Effects - other effects Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22,1729,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1010 mg/kg SEX/DURATION : male 80 day(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - other measures of fertility REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22,1729,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 104 mg/kg SEX/DURATION : female 17-21 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Maternal Effects - other effects Reproductive - Effects on Newborn - other neonatal measures or effects Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 10,446,1992

安全

• 危害码 (欧洲): Xi
• 风险声明 (欧洲): R20/21/22
• 安全声明 (欧洲): S24/25
• WGK德国: 3

合成路线

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制备

化合物(I)和化合物(Ⅱ)进行缩合，然后水解即可得到培垛普利。
化合物(Ⅰ)可由化合物(Ⅲ)出发，经酯化、还原、水解再酯化得到。
化合物(Ⅱ)可由化合物(Ⅳ)和化合物(Ⅶ)进行还原氨解反应得到，收率52%。(可参见Lane C F．Synthesis，1975，135～146)
化合物(Ⅱ)也可由化合物(Ⅷ)和化合物(Ⅸ)进行还原氨解反应得到，收率64.4%。 (可参见Yamada Sun-Ichi，et a1．Tetrahedron Lett，1976，13：997-1000)