124750-92-1

• 常用中文名：氯沙坦
• 常用英文名：EXP 3174
• CAS号：124750-92-1
• 分子式：C₂₂H₂₁ClN₆O₂
• 分子量：436.894
• 相关类别： 原料药 循环系统用药 抗高血压病药
• 发布时间：2018-08-28 04:31:07
• 更新时间：2026-07-06 17:00:10
• Losartan Carboxylic Acid (E-3174) 是 Losartan 的活性羧酸代谢产物,是血管紧张素 Ⅱ 受体 1 型 (AT1) 拮抗剂。对大鼠 AT1B/AT1A 和人 AT1 的 Ki 值分别为 0.97、0.57、0.67 nM。Losartan Carboxylic Acid 阻断血管紧张素II诱导的血管平滑肌细胞 (VSMC) 反应。Losartan Carboxylic Acid 升高血浆肾素活性,降低平均动脉压。

名称

• 中文名: 氯沙坦
• 英文名: 2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid
• 中文别名: 5-羧酸氯沙坦; 阿利沙坦酯杂质 I; EXP-3174、5-羧酸洛沙坦; Lostan Cboxylic Acid (EXP-3174) 氯沙坦羧酸，S5980; 洛沙坦杂质14; 阿利沙坦酯杂质16; 2-丁基-4-氯-1- [2'-(1H-四唑-5-基)联苯-4-基甲基]咪唑-5-羧酸; 5-羧酸洛沙坦; Exp3174 酸性代谢物; 洛沙坦-5-羧酸; 氯沙坦酸; Lostan Cboxylic Acid (EXP-3174) 氯沙坦羧酸,S5980; 1-((2'-(1H-四唑-5-基)-[1,1'-联苯] -4-基)甲基)-2-丁基-4-氯-1H-咪唑-5-羧酸; 羧酸洛沙坦; 氯沙坦羧酸; 2-丁基-4-氯-1-[(2-(1-H-四唑-5-基)[1,1-联苯]-4-基)甲基]-1-H-咪唑-5-羧酸; 洛沙坦杂质
• 英文别名: exp3174; 2-Butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1; 2-Butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]imidazole-5-cboxylic acid; 2-n-butyl-5-chloro-3-[2'-(2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid; E-3174; Lostan Cboxylic Acid Discontinued see product # L470510; Lostan Cboxylic Acid, 10 mM in DMSO; EXP 3174 (LOSTAN CBOXYLIC ACID); Carboxylosartan; 2-Butyl-4-chloro-1-{[2'-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid; Lostan Cboxylic Acid //BP; 2-BUTYL-4-CHLORO-1-[(2'-(1-H-TETRAZOL-5-YL)[1,1'-BIPHENYL]-4-YL)METHYL]-1-H-IMIDAZOLE-5-CBOXYLIC ACID; 1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-4-chloro-1H-imidazole-5-cboxylic acid; ’-biphenyl)-4-yl)methyl); Exp3174; LOSTAN,2-BUTYL-4-CHLORO-1-[(2'-(1-H-TETRAZOL-5-YL)[1,1'-BIPHENYL]-4-YL)METHYL]-1-H-IMIDAZOLE-5-CBOXYLIC ACID; Lostan cboxylic acid, >=; 2-Butyl-4-chloro-1-[[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-cboxylic acid; Lostan cboxylic acidQ: What is Lostan cboxylic acid Q: What is the CAS Number of Lostan cboxylic acid Q: What is the storage condition of Lostan cboxylic acid Q: What e the applications of Lostan cboxylic acid; Lostan Cboxylic Acid; 1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-cboxylic Acid; 2-Butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-imidazole-5-cboxylic acid; Lostan Impurity 14; l-158641; 1H-Imidazole-5-cboxylicacid, 2-butyl-4-chloro-1-[[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]; 2-Butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-cboxylic Acid (Lostan Cboxylic Acid); 2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-cboxylic acid; 2-Butyl-4-chloro-1-[[2(1H-tetrazol-5-yl)[1,1biphenyl]-4-yl]methyl]-1H-imidazole-5-cboxylicAcid; 1H-Imidazole-5-cboxylic acid, 2-butyl-4-chloro-1-((2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl); 1h-imidazole-5-cboxylicacid,2-butyl-4-chloro-1-((2’-(14-tetrazol-5-yl)(1,1; 2-n-butyl-5-chloro-3-[2'-(2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-cboxylic acid; Losartan carboxylic acid; E-3174;EXP-3174;E 3174;EXP 3174;E3174;EXP; e-3174; LOSTAN CBOXY ACID; Lostan Cboxylic Acid (Lostan Cboxylate); Lostan Cboxylic Acid NEW CATALOGUE NUMBER: see product # L470510; ALSTint-A07; 2-Butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-cboxylic Aci; Lostan cboxylic acid in methanol; 2-BUTYL-4-CHLORO-1-[(2'-(1-H-TETRAZOL-5-YL)[1,1'-BIPHENYL]-4-YL)METHYL]-1-H-IMIDAZOLE-5-CBOXYLIC ACID //BP; 1H-Imidazole-5-carboxylic acid,2-butyl-4-chloro-1-((2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl); EXP3174 acid metabolite; E-3174, EXP-3174; Lostan Cboxylic acid Impurity; EXP-3174; Alistan cilexetil impurity I; Lostan acid; 2-Butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-formic acid; E-3174;EXP-3174;E 3174;EXP 3174;E3174;EXP3174;2-BUTYL-4-CHLORO-1-[[2'-(1H-TETRAZOL-5-YL)[1;1'-BIPHENYL]-4-YL]METHYL]-1H-IMIDAZOLE-5-CBOXYLIC ACID; 2-Butyl-3-[[2'-(2H-tetrazol-5-yl)-1,1'-biphenyl-4-yl]methyl]-5-chloro-3H-imidazole-4-cboxylic acid; 2-Butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)-4-biphenylyl]methyl}-1H-imidazole-5-carboxylic acid

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 707.8±70.0 °C at 760 mmHg
• 熔点: 130-132ºC
• 分子式: C₂₂H₂₁ClN₆O₂
• 分子量: 436.894
• 闪点: 381.8±35.7 °C
• 精确质量: 436.141449
• PSA: 109.58000
• LogP: 4.79
• 外观性状: 淡黄色固体
• 蒸汽压: 0.0±2.4 mmHg at 25°C
• 折射率: 1.695
• 储存条件: -20°C Freezer

生物活性

• 描述: Losartan Carboxylic Acid (E-3174) 是 Losartan 的活性羧酸代谢产物,是血管紧张素 Ⅱ 受体 1 型 (AT1) 拮抗剂。对大鼠 AT1B/AT1A 和人 AT1 的 Ki 值分别为 0.97、0.57、0.67 nM。Losartan Carboxylic Acid 阻断血管紧张素II诱导的血管平滑肌细胞 (VSMC) 反应。Losartan Carboxylic Acid 升高血浆肾素活性,降低平均动脉压。
• 相关类别:
  研究领域 >> 心血管疾病
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 血管紧张素受体
• 靶点:

  Angiotensin II receptor type 1[1]

• 体外研究: 氯沙坦羧酸(E-3174)以1.1nm的IC50抑制血管紧张素II与血管平滑肌细胞的特异性结合。氯沙坦羧酸消除血管紧张素Ⅱ诱导的血管平滑肌细胞肌醇磷酸酯的形成。氯沙坦羧酸抑制血管紧张素Ⅱ诱导的细胞内Ca2+浓度升高,IC50为5nm。氯沙坦羧酸比氯沙坦更有效地阻断血管紧张素Ⅱ诱导的Egr-1 mRNA的增加。氯沙坦羧酸抑制血管紧张素Ⅱ诱导的细胞蛋白合成,IC50为3nm[1]。
• 体内研究: 氯沙坦羧酸(E-3174)(0.1 mg/kg；静脉注射,然后0.02 mg/kg/h,持续5.5小时)对血管紧张素i的升压反应产生类似程度的抑制(87±4%)。静脉注射氯沙坦羧酸(0.1 mg/kg+0.01 mg/kg/min)于麻醉犬近期(8.1±0.4天)前壁心肌梗死。治疗开始后1h开始电解损伤左回旋支冠状动脉,导致血栓闭塞和后外侧缺血[4]。动物模型：雌雄各半的杂种犬,体重15-25公斤[3]剂量：0.1毫克/公斤(随后0.02毫克/公斤/小时)静脉注射5.5小时。结果：升压反应降低87±4%。
• 参考文献:

  [1]. Sachinidis A, et al. EXP3174, a metabolite of losartan (MK 954, DuP 753) is more potent than losartan in blockingthe angiotensin II-induced responses in vascular smooth muscle cells. J Hypertens. 1993 Feb;11(2):155-62.

  [2]. Inada Y, et al. Binding of KRH-594, an antagonist of the angiotensin II type 1 receptor, to cloned human and rat angiotensin II receptors. Fundam Clin Pharmacol. 2002 Aug;16(4):317-23.

  [3]. Richard V, et al. Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs. Br J Pharmacol. 1993 Nov;110(3):969-74.

  [4]. Lynch JJ Jr, et al. EXP3174, the AII antagonist human metabolite of losartan, but not losartan nor the angiotensin-converting enzyme inhibitor captopril, prevents the development of lethal ischemic ventricular arrhythmias in a canine model of recent myocardial infarction. J Am Coll Cardiol. 1999 Sep;34(3):876-84.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : NI4004850 CHEMICAL NAME : 1H-Imidazole-5-carboxylic acid, 2-butyl-4-chloro-1-((2'-(14-tetrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)- CAS REGISTRY NUMBER : 124750-92-1 LAST UPDATED : 199712 DATA ITEMS CITED : 1 MOLECULAR FORMULA : C22-H21-Cl-N6-O2 MOLECULAR WEIGHT : 436.94 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 441 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - tremor Lungs, Thorax, or Respiration - respiratory depression REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 28,3959,1994

安全

• 安全声明 (欧洲): 24/25

合成路线

124750-99-8 ~89% 124750-92-1

文献：SHANGHAI ALLIST PHARMACEUTICAL., INC. Patent: EP1988090 A1, 2008 ; Location in patent: Page/Page column 11 ; EP 1988090 A1

114798-26-4 ~78% 124750-92-1

文献：Chen, Liqin; Li, Jian; Shen, Yingzhong Patent: US2008/90885 A1, 2008 ; Location in patent: Page/Page column 2 ;

124750-99-8 ~64% 114798-36-6 124750-92-1

文献：Tetrahedron Letters, , vol. 44, # 6 p. 1149 - 1152

上下游产品

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