74258-86-9

• 常用中文名：阿拉普利
• 常用英文名：Alacepril
• CAS号：74258-86-9
• 分子式：C₂₀H₂₆N₂O₅S
• 分子量：406.49600
• 相关类别： 原料药 循环系统用药 抗高血压病药
• 发布时间：2018-03-17 08:00:00
• 更新时间：2024-01-02 12:42:26
• 阿拉西普利(Cetapril)是一种口服活性血管紧张素转换酶(ACE)抑制剂,具有持久的降压作用[1]。

名称

• 中文名: 阿拉普利
• 英文名: Alacepril
• 中文别名: 2-[[1-(3-乙酰硫基-2-甲基丙酰基)吡咯烷-2-甲酰]氨基]-3-苯丙酸; 阿拉普拉; (S)-N-[1-[3-(乙酰基硫代)-2-甲基-1-氧丙基]-L-脯氨酰]-L-苯丙氨酸
• 英文别名: 1-(d-3-acetylthio-2-methylpropanoyl)-l-prolyl-l-phenylalanine; (S)-N-[1-[3-(acetylthio)-2-methyl-1-oxopropyl]-L-prolyl]-L-phenylalanil; L-Phenylalanine,1-[(2S)-3-(acetylthio)-2-methyl-1-oxopropyl]-L-prolyl; 1-((S)-3-acetylthio-2-methylpropanoyl)-L-prolyl-L-phenylalanine; cetapril; 1-[(2S)-3-(acetylthio)-2-methyl-1-oxopropyl]-L-prolyl-L-phenylalanine; N-[(S)-3-Acetylthio-2-methylpropanoyl]-L-Pro-L-Phe-OH; du1219; Cetapfil; (s)-l-phenylalanin; 1-[(S)-3-Acetylthio-2-methylpropanoyl]-L-Pro-L-Phe-OH; MFCD00869538

物化性质

• 密度: 1.281g/cm3
• 沸点: 679.1ºC at 760 mmHg
• 分子式: C₂₀H₂₆N₂O₅S
• 分子量: 406.49600
• 闪点: 364.5ºC
• 精确质量: 406.15600
• PSA: 129.08000
• LogP: 2.03410
• 折射率: 1.581
• 储存条件: -20°C，干燥，密封
• 分子结构:

  1、 摩尔折射率：105.81

  2、 摩尔体积（cm³/mol）：317.3

  3、 等张比容（90.2K）：873.6

  4、 表面张力（dyne/cm）：57.4

  5、 极化率（10-24cm3）：41.94

• 更多:

  1.性状：从乙醇-n-己烷结晶，白色结晶或结晶性粉末，无气味或略有异味，味微苦。

  2.熔点（℃）：155-156。

  3.比旋光度（C=1.02，乙醇)）：-81.3°。

  4.溶解度：易溶于氯仿或甲醇，较易溶于乙醇，较难溶于丙酮，难溶于水，极难溶于乙醚

生物活性

• 描述: 阿拉西普利(Cetapril)是一种口服活性血管紧张素转换酶(ACE)抑制剂,具有持久的降压作用[1]。
• 相关类别:
  研究领域 >> 心血管疾病
  信号通路 >> 代谢酶/蛋白酶 >> 血管紧张素转换酶(ACE)
• 体内研究: 每日连续口服一次(1-2 mg/kg/d)可证实阿拉西普利对肾性高血压大鼠的长期降压作用。在肾性高血压犬中,阿拉西普利(3 mg/kg)表现出稳定和持续的降压作用,其作用时间长于卡托普利[1]。
• 参考文献:

  [1]. Takeyama K, et al. Antihypertensive activity of alacepril, an orally active angiotensin converting enzyme inhibitor, in renal hypertensive rats and dogs. Arzneimittelforschung. 1985;35(10):1502-1507.

毒性和生态

毒理学数据: 急性毒性LD50大鼠，小鼠(mg／kg)：＞5000，＞5000口服；＞3000，＞3000皮下注射；约2000，约3000腹腔注射。 CHEMICAL IDENTIFICATION RTECS NUMBER : SQ7325700 CHEMICAL NAME : L-Phenylalanine, N-(1-(3-(acetylthio)-2-methyl-1-oxopropyl)-L-prolyl)- , (S)- CAS REGISTRY NUMBER : 74258-86-9 LAST UPDATED : 199612 DATA ITEMS CITED : 12 MOLECULAR FORMULA : C20-H26-N2-O5-S MOLECULAR WEIGHT : 406.54 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 : >5 gm/kg TOXIC EFFECTS : Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea 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: 13,7033,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1872 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - hypermotility, diarrhea 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: 13,7033,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Skin and Appendages - dermatitis, other (after systemic exposure) Skin and Appendages - hair 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: 13,7033,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) 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: 13,7033,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2921 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - hypermotility, diarrhea 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: 13,7033,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Skin and Appendages - dermatitis, other (after systemic exposure) Skin and Appendages - hair 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: 13,7033,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >1 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #7477 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 : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,64,1990 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 54600 mg/kg/26W-I TOXIC EFFECTS : Cardiac - changes in heart weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Nutritional and Gross Metabolic - changes in sodium 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: 13,7097,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 9 gm/kg/30D-I TOXIC EFFECTS : Cardiac - changes in heart weight Blood - normocytic anemia Blood - other changes 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: 13,7041,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 18 gm/kg/30D-C TOXIC EFFECTS : Gastrointestinal - other changes Liver - other changes Related to Chronic Data - death 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: 13,7061,1985 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 26 gm/kg SEX/DURATION : female 17-21 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : 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: 13,5711,1985

安全

• 危害码 (欧洲): Xn
• 风险声明 (欧洲): R22:Harmful if swallowed.
• WGK德国: 3
• RTECS号: UO3516500

合成路线

74258-85-8 ~99% 74258-86-9

文献：NICOX S.A. Patent: WO2004/106300 A1, 2004 ; Location in patent: Page 65 ;

64805-64-7 13589-02-1 ~% 74258-86-9

文献：US4248883 A1, ;

74345-73-6 13589-02-1 ~65% 74258-86-9

文献：Sawayama; Itokawa; Shimada; Doi; Kimura; Nishim ura Chemical and Pharmaceutical Bulletin, 1990 , vol. 38, # 2 p. 529 - 531

7524-50-7 ~% 74258-86-9

文献：Chemical and Pharmaceutical Bulletin, , vol. 38, # 2 p. 529 - 531

129398-84-1 ~% 74258-86-9

文献：Chemical and Pharmaceutical Bulletin, , vol. 38, # 2 p. 529 - 531

13200-83-4 ~% 74258-86-9

文献：Chemical and Pharmaceutical Bulletin, , vol. 38, # 2 p. 529 - 531

147-85-3 ~% 74258-86-9

文献：Chemical and Pharmaceutical Bulletin, , vol. 38, # 2 p. 529 - 531

上下游产品

上游产品  7
74258-85-8 64805-64-7 13589-02-1 74345-73-6
7524-50-7 13200-83-4 147-85-3
下游产品  0

制备

1.0g化合物(I)溶于含有N-甲基吗啉的二氯甲烷中，加入0.57g化合物(Ⅱ)，反应1h，得化合物(Ⅲ)。2.5g化合物(Ⅲ)在三氟乙酸-苯甲醚中反应1h，得1.8g阿拉普利。