脒氯嗪

中文名称:

脒氯嗪

中文同义词:

胍酰吡嗪;脒氯嗪;阿米洛利杂质;脒氯嗪 阿米洛利杂质

英文名称:

AMILORIDE

英文同义词:

3,5-Diamino-6-chloro-N-(aminoiminomethyl)-2-pyrazinecarboxamide;3,5-Diamino-6-chloro-N-(diaminomethylene)pyrazinecarboxamide;MK-870;3,5-diamino-N-carbamimidoyl-6-chloropyrazine-2-carboxamide;AMILORIDE;N-amidino-3,5-diamino-6-chloropyrazine-2-carboxamide;2-Pyrazinecarboxamide, 3,5-diamino-N-(aminoiminomethyl)-6-chloro-

CAS号:

2609-46-3

分子式:

C6H8ClN7O

分子量:

229.63

EINECS号:

220-024-7

相关类别:

化工原料

Mol文件:

2609-46-3.mol

熔点 

240.5-241.5°

密度 

2.11±0.1 g/cm3(Predicted)

酸度系数(pKa)

pKa 8.7 (Uncertain)

水溶解性 

659g/L(25 ºC)

CAS 数据库

2609-46-3(CAS DataBase Reference)

应用

脒氯嗪为阿米洛利生产过程中产生的杂质。盐酸阿米洛利具有良好的保钾排钠功能，可选择性作用于肾小管的细胞内膜上，能阻滞钠进入细胞内，从而降低细胞腔壁负电势，使K+，H+排泄受阻而显示保K+作用。

制备

阿米洛利杂质脒氯嗪制备如下：将N-脒基-3，5-二氨基-6-碘-2-吡嗪甲酰胺盐酸盐（3.50g，0.01摩尔），氯化亚铜（0.024摩尔）和六甲基磷酰胺（30ml）并在100℃加热保持15分钟。冷却至环境温度后，将反应混合物添加至氰化钠水溶液（100mL）中，在25℃下搅拌1/2小时，并通过抽滤收集固体沉淀物，用水洗涤，然后用氯仿洗涤。将产物溶于沸水（50毫升）中，用6NHCl处理并冷却，得到1.43克脒氯嗪。

生物活性

Amiloride (MK-870) 是上皮钠通道 (ENaC) 和尿激酶型纤溶酶原激活物受体 (uTPA) 的抑制剂。Amiloride 是 polycystin-2 (PC2; TRPP2) 通道阻断剂。

靶点

ENaC; uTPA; polycystin-2(TRPP2)

体外研究

Amiloride blocks δβγ channels with an IC 50 of 2.6 μM (58, 71, 75, 134, 148). The K i of amiloride for δβγ ENaC is 26-fold that of αβγ channels (0.1 μM for αβγ ENaC). Amiloride blockade of δβγ ENaC is much more voltage dependent compared with the αβγ channel. The K i of amiloride for δαβγ channels is 920 and 13.7 μM at -120 and +80 mV, respectively, which significantly differs from that of both αβγ and δβγ channels. Amiloride is a relatively selective inhibitor of the epithelial sodium channel (ENaC) with an IC 50 (the concentration required to reach 50% inhibition of an ion channel) in the concentration range of 0.1 to 0.5 μM. Amiloride is a relatively poor inhibitor of the the Na + /H + exchanger (NHE) with an IC 50 as low as 3 μM in the presence of a low external [Na + ] but as high as 1 mM in the presence of a high [Na + ]. Amiloride is an even weaker inhibitor of the Na + /Ca 2+ exchanger (NCX), with an IC 50 of 1 mM. Amiloride (1 μM) and submicromolar doses of Benzamil (30 nM), doses known to inhibit the ENaC, inhibit the myogenic vasoconstriction response to increasing perfusion pressure by blocking the activity of ENaC proteins. Amiloride completely inhibits Na + influx in doses known to be relatively specific for ENaC (1.5 μM) in vascular smooth muscle cells (VSMC).

体内研究

Amiloride (1 mg/kg/day) subcutaneously is found to reverse the initial increases in collagen deposition and prevent any further increases in the DOCA-salt hypertensive rat. Amiloride delays the onset of proteinuria and improved brain and kidney histologic scores in the saline-drinking, stroke-prone spontaneously hypertensive rats (SHRSP) compared with controls. Amiloride antagonizes or prevents actions of aldosterone in these cells and in cardiovascular and renal tissues in animals with salt-dependent forms of hypertension.