208848-19-5

中文名称 FRESELESTAT

英文名称 FRESELESTAT

CAS 208848-19-5

分子式 C23H28N6O4

分子量 452.51

MOL 文件 208848-19-5.mol

208848-19-5 结构式

基本信息物理化学性质常见问题列表

基本信息

中文别名

夫瑞司他 ONO6818

英文别名

ONO6818
ONO 6818
ONO-6818
ONO-PO-736
Freselesat
FRESELESTAT
5-Amino-N-[1-[[5-(1,1-dimethylethyl)-1,3,4-oxadiazol-2-yl]carbonyl]-2-methylpropyl]-6-oxo-2-phenyl-1(6H)-pyrimidineacetamide
1(6H)-PyriMidineacetaMide,5-aMino-N-[1-[[5-(1,1-diMethylethyl)-1,3,4-oxadiazol-2-yl]carbonyl]-2-Methylpropyl]-6-oxo-2-phenyl-

物理化学性质

熔点151-153oC

密度1.32±0.1 g/cm3(Predicted)

储存条件-20°C冷冻

溶解度可溶于DMSO（少许）、甲醇（少许）

酸度系数(pKa)12.43±0.46(Predicted)

形态固体

颜色灰白色至淡黄色

常见问题列表

生物活性

Freselestat (ONO-6818) 是一种有效且具有口服活性的嗜中性粒细胞弹性蛋白酶 (neutrophil elastase) 抑制剂，Ki 为 12.2 nM。Freselestat 对其他蛋白酶（例如胰蛋白酶，蛋白酶3，胰弹性蛋白酶，纤溶酶，凝血酶，胶原酶，组织蛋白酶G和鼠巨噬细胞弹性蛋白酶）的活性低 100 倍以上，并具有有效的抗炎活性。

靶点

Ki: 12.2 nM (Neutrophil elastase)

体外研究

Simulated extracorporeal circulation is established by recirculating fresh heparinized (3.75 U/mL) human blood for 120 minutes in a membrane oxygenator and a roller pump with and without 1.0 μM of Freselestat (ONO-6818). Neutrophil elastase levels are significantly lower in the Freselestat group. Freselestat significantly reduces interleukin 8 and C5b-9 production. Freselestat does not modulate changes of CD11b and L-selectin during recirculation.

体内研究

Freselestat (ONO-6818; 10-100 mg/kg; oral administration; daily; for 8 weeks) treatment attenuates dose-dependently HNE-induced increases in lung myeloperoxidase activity, hemoglobin, and neutrophil count in bronchoalveolar lavage fluid. ONO-6818 inhibits acute lung injury induced by HNE by minimizing lung hemorrhage and accumulation of neutrophils in the lung.

Animal Model:	Male Wistar rats (228 g) induced by human neutrophil elastase (HNE)
Dosage:	10 mg/kg, 100 mg/kg
Administration:	Oral administration; daily; for 8 weeks
Result:	Attenuated dose-dependently HNE-induced increases in lung myeloperoxidase activity, hemoglobin, and neutrophil count in bronchoalveolar lavage fluid.