195529-54-5

中文名称 A192621

英文名称 A192621

CAS 195529-54-5

分子式 C33H38N2O6

分子量 558.66

MOL 文件 195529-54-5.mol

195529-54-5 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

化合物 T14068

英文别名

A192621
A192621,CID 5310991
A192621 >=98 (HPLC)
(2R,3R,4S)-4-(1,3-BENZODIOXOL-5-YL)-1-[2-[(2,6-DIETHYLPHENYL)AMINO]-2-OXOETHYL]-2-(4-PROPOXYPHENYL)PYRROLIDINE-3-CARBOXYLIC ACID
3-Pyrrolidinecarboxylic acid, 4-(1,3-benzodioxol-5-yl)-1-[2-[(2,6-diethylphenyl)amino]-2-oxoethyl]-2-(4-propoxyphenyl)-, (2R,3R,4S)-

物理化学性质

沸点738.3±60.0 °C(Predicted)

密度1.233±0.06 g/cm3(Predicted)

储存条件-20°C

酸度系数(pKa)3.52±0.60(Predicted)

形态粉末

颜色白色至米色

常见问题列表

生物活性

A-192621 是一种有效的非肽，口服活性，选择性内皮素 B (ETB) 受体拮抗剂，IC50 为 4.5 nM，Ki 为 8.8 nM。A-192621 的选择性比 ETA 高 636 倍 (IC50 为 4280 nM，Ki 为 5600 nM)。A-192621 促进 PASMC 细胞凋亡，并引起动脉血压升高和血浆 ET-1 水平升高。

靶点

ET _B

4.5 nM (IC ₅₀ )

ET _B

8.8 nM (Ki)

ET _A

4280 nM (IC ₅₀ )

ET _A

5600 nM (Ki)

体外研究

A-192621 (1-100 μM; 48 hours; PASMCs) treatment markedly reduces the cell viability of PASMCs in a dose-dependent manner.
A-192621 (1-100 μM; 48 hours; PASMCs) treatment significantly increases the caspase-3/7 activity and cleaved caspase-3 expression in PASMCs. A-192621 induces apoptosis in a dose-dependent manner and increases the cells' susceptibility to apoptosis by Doxorubicin treatment.

Cell Viability Assay

Cell Line:	Pulmonary arterial smooth muscle cells (PASMCs) with Doxorubicin
Concentration:	1 μM, 10 μM, 50 μM, 100 μM
Incubation Time:	72 hours
Result:	The viability of PASMCs was significantly decreased in a dose-dependent manner.

Western Blot Analysis

Cell Line:	Pulmonary arterial smooth muscle cells (PASMCs) with Doxorubicin
Concentration:	1 μM, 10 μM, 100 μM
Incubation Time:	72 hours
Result:	The caspase-3/7 activity in PASMCs was significantly increased in a dose-dependent manner.

体内研究

A-192621 (30-100 mg/kg; oral administration; daily; for 3 days; male Sprague-Dawley rats) treatment inhibits both dilatory and pressor responses induced by S6c mediated by ET _B with an ED ₅₀ value of 30 mg/kg, and failed to inhibit the ET-1-induced pressor response mediated by ET _A . A-192621 alone causes elevation of arterial blood pressure and an elevation in the plasma ET-1 level in the conscious normotensive rat.

Animal Model:	Male Sprague-Dawley rats (250-350 g)
Dosage:	30 mg/kg 100 mg/kg
Administration:	Oral administration; daily; for 3 days
Result:	Inhibited both dilatory and pressor responses induced by S6c mediated by ET _B with an ED ₅₀ value of 30 mg/kg.