2,2'-((((((亚甲基双(2-氯-4,1-亚苯基))二(氮烷二基))二(羰基))双(氮烷二 | 245075-84-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2,2'-((((((亚甲基双(2-氯-4,1-亚苯基))二(氮烷二基))二(羰基))双(氮烷二
• 英文名称: 2,2'-(4,4'-(4,4'-methylenebis(2-chloro-4,1-phenylene))bis(azanediyl)bis(oxomethylene)bis(azanediyl)bis(4,1-phenylene))bis(oxy)bis(2-Methylpropanoic acid)
• 英文别名: 2-[4-[[4-[[4-[[4-(2-carboxypropan-2-yloxy)phenyl]carbamoylamino]-3-chlorophenyl]methyl]-2-chlorophenyl]carbamoylamino]phenoxy]-2-methylpropanoic acid
• CAS: 245075-84-7
• 化学式: C₃₅H₃₄Cl₂N₄O₈
• 分子量: 709.6
• InChiKey: WJDMCXSGUCNRPZ-UHFFFAOYSA-N

物化性质

• 沸点：
  726.0±60.0 °C(Predicted)
• 密度：
  1.448±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：≥ 100 mg/mL (140.93 mM)；水：< 0.1 mg/mL（不溶）

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  49
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  175
• 氢给体数：
  6
• 氢受体数：
  8

制备方法与用途

生物活性

LR-90 是晚期糖基化终产物 (advanced glycation end product (AGE)) 抑制剂，能够抑制人单核细胞的炎症反应。LR-90 也可用于糖尿病动物模型研究。

靶点

AGE

体外研究

LR-90 (0, 25, 50, 100, and 200 μM) inhibits RAGE, MCP-1, COX-2, IP-10 and NOX2 mRNA expression in THP-1 cells in a dose-dependent manner, after pretreatment 1 h befor S100b stimulatation for 4 hours.
LR-90 (0, 25, 50, 100, and 200 μM) dose-dependently and significantly blocks THP-1 cells adherence to endothelial cells after pretreatment 1 h befor S100b stimulatation for 24 hours.
LR-90 (0, 25, 50, 100, and 200 μM, for 24 hours) shows no effect on the cell viability of THP-1 cells.

Cell Viability Assay

Cell Line:	THP-1 cells
Concentration:	0, 25, 50, 100, and 200 μM
Incubation Time:	24 hours
Result:	Showed no cytotoxicity to THP-1 cells.

RT-PCR

Cell Line:	THP-1 cells
Concentration:	0, 25, 50, 100, and 200 μM
Incubation Time:	One hour before S100b addition for 4 hours
Result:	Dose-dependently inhibited mRNA expression of RAGE, MCP-1, COX-2, IP-10, and NOX2 stimulated with S100b.

体内研究

LR-90 (50 mg/L, p.o. for 27 weeks) significantly reduces plasma lipids, modestly affects hyperglycaemia in ZDF rats.
LR-90 (50 mg/L) decreases renal AGE, AGER and lipid peroxidation.

Animal Model:	Male ZDF rats (13 to 40 weeks)
Dosage:	50 mg/L
Administration:	P.O. for 27 weeks
Result:	Significantly reduced plasma triacylglycerol and cholesterol by ∼55% and ∼30%, respectively. Modestly affected hyperglycaemia and blood pressure. Lowered the body weight.