中文名 | BX471 |
英文名 | BX471 |
别名 | 化合物BX-471 (2R)-1-[[[4-氯-2-(脲基)苯氧基]甲基]羰基]-2-甲基-4-(4-氟苄基)哌嗪 (R)-1-[5-氯-2-[2-[4-(4-氟苄基)-2-甲基哌嗪-1-基]-2-氧代乙氧基]苯基]脲 |
英文别名 | BX471 ZK811752 (BX471) BX471(ZK-811752) (5-Chloro-2-{2-[4-(4-fluoro-benzyl)-2-Methyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-urea (2R)-1-[[[4-Chloro-2-(ureido)phenoxy]methyl]carbonyl]-2-methyl-4-(4-fluorobenzyl)piperazine N-[5-chloro-2-[2-[(2R)-4-[(4-fluorophenyl)methyl]-2-methyl-1-piperazinyl]-2-oxoethoxy]phenyl]-urea Urea, N-[5-chloro-2-[2-[(2R)-4-[(4-fluorophenyl)Methyl]-2-Methyl-1-piperazinyl]-2-oxoethoxy]phenyl]- Piperazine,1-[[2-[(aminocarbonyl)amino]-4-chlorophenoxy]acetyl]-4-[(4-fluorophenyl)methyl]-2-methyl-, (2R)- (2R)-1-[[2-[(Aminocarbonyl)amino]-4-chlorophenoxy]acetyl]-4-[(4-fluorophenyl)methyl]-2-methylpiperazine ZK811752 (BX471) |
CAS | 217645-70-0 |
化学式 | C21H24ClFN4O3 |
分子量 | 434.89 |
密度 | 1.346±0.06 g/cm3(Predicted) |
沸点 | 593.5±50.0 °C(Predicted) |
溶解度 | DMSO: ≥ 25 mg/mL |
酸度系数 | 13.66±0.70(Predicted) |
存储条件 | Inert atmosphere,2-8°C |
外观 | 白色粉末 |
颜色 | white to tan |
体外研究 | BX471 is a potent functional antagonist based on its ability to inhibit a number of CCR1-mediated effects including Ca 2+ mobilization, increase in extracellular acidification rate, CD11b expression, and leukocyte migration. BX471 demonstrats a greater than 10,000-fold selectivity for CCR1 compared with 28 G-protein-coupled receptors. BX471 is also able to displace 125 I-MIP-1α/CCL3 binding to mouse CCR1 in a concentration-dependent manner with a K i of 215±46 nM. Increasing concentrations of BX471 inhibits the Ca 2+ transients induced by MIP-1α/CCL3 in both human and mouse CCR1 with IC 50 of 5.8±1 nM and 198±7 nM, respectively. BX471 (0.1-10 μM) shows a dose-dependent inhibition of RANTES-mediated and shear-resistant adhesion on IL-1β-activated microvascular endothelium in shear flow in isolated blood monocytes. BX471 also inhibits the RANTES-mediated adhesion of T lymphocytes to activated endothelium. |
体内研究 | BX471 (4 mg/kg, p.o. or i.v.) is orally active with a bioavailability of 60% in dogs. Furthermore, BX471 effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis. BX471 (20 mg/kg, s.c.) reaches peak plasma levels of 9 μM by around 30 minutes, and this rapidly declines to approximately 0.4 μM after 2 hours. From 4 to 8 hours the drug plasma levels drops to 0.1 μM or lower. Mice treated with 20 mg/kg of BX471 for 10 days shows a reduction of interstitial CD45 positive leukocytes of approximately 55%. BX471 has a borderline significant effect on the number of CCR5-positive CD8 cells in the peripheral blood. BX471 reduces the amount of FSP1-positive cells by 65% in UUO kidneys as compared with vehicle control. Pretreatment witih BX471 reduces macrophage and neutrophil accumulation in kidney after ischemia-reperfusion injury. |
危险品标志 | Xn - 有害物品 N - 危害环境的物品 |
风险术语 | R22 - 吞食有害。 R50 - 对水生生物有极高毒性。 |
安全术语 | 61 - 避免释放至环境中。参考特别说明/安全数据说明书。 |
WGK Germany | 3 |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.299 ml | 11.497 ml | 22.994 ml |
5 mM | 0.46 ml | 2.299 ml | 4.599 ml |
10 mM | 0.23 ml | 1.15 ml | 2.299 ml |
5 mM | 0.046 ml | 0.23 ml | 0.46 ml |
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