中文名称:

奥斯他伟酸

中文同义词:

奥斯他伟酸;奥司他韦酒石酸盐;奥司他韦10;奥斯他伟酸(奥司他韦羧酸);奥司他韦羧酸;奥司他韦酸;奥塞米韦酸;奥司他韦杂质C(EP)

英文名称:

OSELTAMIVIR ACID

英文同义词:

(3R,4R,5S)-4-acetamido-5-amino-3;Oseltamivir Phosphate Impurity Ⅲ;(3R,4R,5S)-4-(Acetylamino)-5-amino-3-(1-ethylpropoxy)-1-cyclohexence-1-carboxylic Acid;Oseltamivir Impurity C (EP);Oseltamivir Carboxylic Acid HCl;GS 4071;RO 64-0802;OSELTAMIVIR CARBOXYLATE;(3R,4R,5S)-4-acetamido-5-amino-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylic acid;(3R,4R,5S)-4-Acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohex-ene-1-carboxylic acid

CAS号:

187227-45-8

分子式:

C14H24N2O4

分子量:

284.35

EINECS号:

相关类别:

杂质对照品;奥司他韦;对照品-杂质对照品;医药原料;Various Metabolites and Impurities;Metabolites;Amines;Intermediates Fine Chemicals;Metabolites Impurities;Pharmaceuticals

Mol文件:

187227-45-8.mol

熔点 

183-185°C

沸点 

508.7±50.0 °C(Predicted)

密度 

1.15±0.1 g/cm3(Predicted)

储存条件 

Keep in dark place,Sealed in dry,2-8°C

形态

neat

酸度系数(pKa)

4.13±0.60(Predicted)

EPA化学物质信息

1-Cyclohexene-1-carboxylic acid, 4-(acetylamino)-5-amino-3-(1-ethylpropoxy)-, (3R,4R,5S)- (187227-45-8)

产品描述

奥司他韦酸是制备奥司他韦的中间体。磷酸奥司他韦是由瑞士罗氏公司研发推出，磷酸奥司他韦具有很强的抑制神经氨酸酶的活性，对A、B型流感病毒均有效。

生物活性

Oseltamivir acid (GS 4071)，Oseltamivir phosphate 的活性代谢产物, 是流感病毒神经氨酸酶 (IC50=2 nM) 的口服生物有效的，选择性的抑制剂，对流感病毒 A 和 B 都有活性。

靶点

IC50: 2 nM (influenza virus neuraminidase)

体外研究

Oseltamivir acid inhibits virus replication in vitro and in vivo. Influenza B and A/H1N1 viruses appeare to be sensitive to Oseltamivir (mean B IC 50 value: 13 nM; mean H1N1 IC 50 value: 1.34 nM), while A/H1N2 and A/H3N2 viruses are more sensitive to Oseltamivir (mean H3N2 IC 50 value: 0.67 nM; mean H1N2 IC 50 value: 0.9 nM). In neuraminidases inhibition assays with influenza A viruses, the IC 50 of RWJ-270201 (approximately 0.34 nM) is comparable to that of Oseltamivir carboxylate (0.45 nM) For influenza B virus isolates, the IC 50 of RWJ-270201 (1.36 nM) is comparable to that of Zanamivir (2.7 nM) and less than that of Oseltamivir carboxylate (8.5 nM).

体内研究

Oseltamivir (0.1, 1, or 10 mg/kg/day, twice daily by oral gavage) produces a dose-dependent antiviral effect against Vietnam/1203/04 (VN1203/04) virus. The 5-day regimen at 10 mg/kg/day protects 50% of mice; deaths in this treatment group are delayed and indicated the replication of residual virus after the completion of treatment. Eight-day regimens improved Oseltamivir efficacy, and dosages of 1 and 10 mg/kg/day significantly reduced virus titers in organs and provided 60% and 80% survival rates, respectively. In the pharmacokinetic study, after the oral administration of 1,000 mg/kg Oseltamivir, peak plasma concentrations are reached at 2 h postdose for Oseltamivir and 8 h for Oseltamivir carboxylate (OC). Rats are exposed to Oseltamivir over the whole sampling interval and had a ~2.7-fold-higher rate of exposure to OC than Oseltamivir. In CSF, peak concentrations are reached at 2 h postdose for Oseltamivir and 6 h for OC. CSF/plasma exposure ratios (AUC 0-8 h ) are ~0.07 for Oseltamivir and 0.007 for OC. In perfused brain samples, peak concentrations are reached at 8 h postdose for Oseltamivir and 6 h for OC. Brain/plasma exposure ratios (AUC 0-8 h ) of ~0.12 for Oseltamivir and 0.01 for OC are recorded. Corresponding CSF/brain exposure ratios ranged between ~0.55 and 0.64 for both analytes. A further group of animals that received a single oral administration of Oseltamivir at a lower dose produced similar results.