83647-97-6

• 常用中文名：螺普利
• 常用英文名：Spirapril
• CAS号：83647-97-6
• 分子式：C₂₂H₃₀N₂O₅S₂
• 分子量：466.61400
• 相关类别： 原料药 循环系统用药 抗高血压病药
• 发布时间：2018-04-03 08:00:00
• 更新时间：2024-01-03 18:02:01
• Spirapril是一种有效的跨血脑屏障血管紧张素转换酶(ACE)抑制剂,具有降压活性。Spirapril与ACE竞争性结合,阻止血管紧张素I转化为血管紧张素II。斯派瑞普是斯派瑞拉的口服活性前药,可用于研究高血压、充血性心力衰竭[1][2][3]。

名称

• 中文名: 螺普利
• 英文名: (8S)-7-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid
• 中文别名: 斯匹诺利; (8S-(7(R*(R*)),8R*))-7-(2-((1-(乙氧羰基)-3-苯基丙基)氨基)-1-氧代丙基)-1,4-二硫杂-7-氮杂螺[4.4]壬烷-8-羧酸; [8S-[7[R^^(R^^)],8R^^]]-7-[2-[[I-(乙氧羰基)-3-苯基丙基]氨基]-1-氧丙基]-1,4-二硫-7-氮杂螺[4.4]壬-8-羧酸
• 英文别名: Renormax; Spirapril [INN:BAN]; Espirapril [Spanish]; Setrilan; Spirapril (INN); Not established; Spiraprilum [Latin]; Sandopril; Spirapril

物化性质

• 密度: 1.32 g/cm3
• 沸点: 697.8ºC at 760 mmHg
• 分子式: C₂₂H₃₀N₂O₅S₂
• 分子量: 466.61400
• 闪点: 375.8ºC
• 精确质量: 466.16000
• PSA: 146.54000
• LogP: 2.71960
• 折射率: 1.621
• 储存条件: -20°C
• 分子结构:

  1、 摩尔折射率：123.88

  2、 摩尔体积（cm³/mol）：351.9

  3、 等张比容（90.2K）：988.2

  4、 表面张力（dyne/cm）：62.1

  5、 极化率（10-24cm3）：49.11

生物活性

• 描述: Spirapril是一种有效的跨血脑屏障血管紧张素转换酶(ACE)抑制剂,具有降压活性。Spirapril与ACE竞争性结合,阻止血管紧张素I转化为血管紧张素II。斯派瑞普是斯派瑞拉的口服活性前药,可用于研究高血压、充血性心力衰竭[1][2][3]。
• 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: Spirapril(喂食针；10 mg/kg；3周)减少TGM123小鼠的酒精摄入,但不会减少TLM小鼠的酒精消耗[2]。Spirapril显示,接受治疗的小鼠脑膜ACE活性降低40.2%[2]。在实验中,Spirapril可以穿过血脑屏障并抑制转基因效应[2]。Spirapril可预防自发性高血压大鼠左心室肥厚,减少心肌损伤并促进血管生成[3]。
• 参考文献:

  [1]. Noble S, Sorkin EM. Spirapril. A preliminary review of its pharmacology and therapeutic efficacy in the treatment of hypertension. Drugs. 1995 May;49(5):750-66.

  [2]. Maul B, et al. Alcohol consumption is controlled by angiotensin II. FASEB J. 2001 Jul;15(9):1640-2.

  [3]. Olivetti G, et al. Spirapril prevents left ventricular hypertrophy, decreases myocardial damage and promotes angiogenesis in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1993 Mar;21(3):362-70.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : JO4925000 CHEMICAL NAME : 1,4-Dithia-7-azaspiro(4,4)nonane-8-carboxylic acid, 7-(2-((1-(ethoxycarbonyl)-3-phenylpropyl) amino)-1-oxopropyl)-, (8S-(7(R*(R*)),8R*))- CAS REGISTRY NUMBER : 83647-97-6 LAST UPDATED : 199612 DATA ITEMS CITED : 6 MOLECULAR FORMULA : C22-H30-N2-O5-S2 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 : >2500 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 5,98,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 600 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 5,98,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >2500 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 5,98,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 400 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 5,98,1985 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 13500 mg/kg/90D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes Blood - changes in erythrocyte (RBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 5,98,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 5400 mg/kg/90D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes REFERENCE : TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 5,98,1985

合成路线

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制备

化合物(I)和乙二硫醇，在含对甲苯磺酸的乙酸中反应，得到化合物(Ⅱ)。再经溴化氢-乙酸脱去保护基，得到化合物(Ⅲ)。(Ⅲ)和化合物(Ⅳ)缩合，生成物(V)再经水解，得到化合物(Ⅵ)。然后经溴化氢-乙酸脱去保护基，得到化合物(Ⅶ)。最后和2-氧-4-苯基丁酸乙酯，在氰三氢硼钠存在下，进行还原烷化，得到螺普利。