N-[(4-chloro-2-methylphenyl)methyl]-1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine
| 中文名称 | N-[(4-chloro-2-methylphenyl)methyl]-1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine |
|---|---|
| 中文同义词 | 化合物 T11490 |
| 英文名称 | N-[(4-chloro-2-methylphenyl)methyl]-1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine |
| 英文同义词 | N-[(4-chloro-2-methylphenyl)methyl]-1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine;GSK-2945;GSK-2945 (GSK2945 );2-Thiophenemethanamine, N-[(4-chloro-2-methylphenyl)methyl]-N-[(4-chlorophenyl)methyl]-5-nitro-;GSK 2945 DISCONTINUED. Please see G797405 |
| CAS号 | 1438071-12-5 |
| 分子式 | C20H18Cl2N2O2S |
| 分子量 | 421.34 |
| EINECS号 | |
| 相关类别 | |
| Mol文件 | 1438071-12-5.mol |
| 结构式 | ![N-[(4-chloro-2-methylphenyl)methyl]-1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine 结构式](CAS/20180601/GIF/1438071-12-5.gif) |
N-[(4-chloro-2-methylphenyl)methyl]-1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine 性质
| 沸点 | 525.0±45.0 °C(Predicted) |
|---|---|
| 密度 | 1.363±0.06 g/cm3(Predicted) |
| 溶解度 | 可溶于乙腈（轻微）、DMSO（轻微、加热）、甲醇（轻微、超声处理） |
| 酸度系数(pKa) | 5.23±0.50(Predicted) |
| 形态 | 固体 |
| 颜色 | 灰白色至浅米色 |
| 稳定性 | 吸湿性 |
N-[(4-chloro-2-methylphenyl)methyl]-1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine 用途与合成方法
GSK2945 是一类叔胺，是一种高度特异性的 Rev-erbα/REV-ERBα (小鼠/人反向成红细胞病病毒α) 拮抗剂， 其 EC50 值分别为 21.5 μM 和 20.8 μM。GSK2945 可增强胆固醇 7α-羟化酶 (CYP7A1) 水平和胆固醇代谢。
GSK2945 dose-dependently enhances the transcriptional activity of Rev-erbα and a Bmal1 (a target gene of REV-ERBs) luciferase reporter (
EC
50
of 2.05 μM).
GSK2945 (20 μM; 12 hours and 24 hours; mouse and human primary hepatocytes) treatment increases levels of Cyp7a1/CYP7A1 in mouse and human primary hepatocytes. GSK2945 (20 μM) treatment also increases Lrh-1/LRH-1 (a known hepatic activator of Cyp7a1/CYP7A1) mRNA and protein.
RT-PCR
| Cell Line: | Mouse (male, CD1) and human (male, Caucasian) primary hepatocytes |
| Concentration: | 20 μM |
| Incubation Time: | 12 hours and 24 hours |
| Result: | Led to significant increases in mRNA and protein (at 24-h) expression of Cyp7a1. mRNA and protein (at 24-h) levels of CYP7A1 were increased in human primary hepatocyte. Lrh-1/LRH-1 was upregulated. |
GSK2945 (0-10 mg/kg; intraperitoneal injection; twice every day; for 7 days; male C57BL/6 mice) treatment increases hepatic mouse cholesterol 7α-hydroxylase (Cyp7a1) level and lowers plasma cholesterol in wild-type mice.
| Animal Model: | Male C57BL/6 mice (8-10 weeks of age) |
| Dosage: | 0 mg/kg or 10 mg/kg |
| Administration: | Intraperitoneal injection; twice every day; for 7 days |
| Result: | Increased hepatic mouse cholesterol 7α-hydroxylase (Cyp7a1) level and lowered plasma cholesterol in wild-type mice. |