2609-46-3
基本信息
脒氯嗪
N-amidino-3,5-diamino-6-chloropyrazine-2-carboxamide
3,5-Diamino-6-chloro-N-(aminoiminomethyl)-2-pyrazinecarboxamide
3,5-Diamino-6-chloro-N-(diaminomethylene)pyrazinecarboxamide
MK-870
物理化學性質(zhì)
常見問題列表
脒氯嗪為阿米洛利生產(chǎn)過程中產(chǎn)生的雜質(zhì)。鹽酸阿米洛利具有良好的保鉀排鈉功能,可選擇性作用于腎小管的細胞內(nèi)膜上,能阻滯鈉進入細胞內(nèi),從而降低細胞腔壁負電勢,使K+,H+排泄受阻而顯示保K+作用。
阿米洛利雜質(zhì)脒氯嗪制備如下:將N-脒基-3,5-二氨基-6-碘-2-吡嗪甲酰胺鹽酸鹽(3.50g,0.01摩爾),氯化亞銅(0.024摩爾)和六甲基磷酰胺(30ml)并在100℃加熱保持15分鐘。冷卻至環(huán)境溫度后,將反應混合物添加至氰化鈉水溶液(100mL)中,在25℃下攪拌1/2小時,并通過抽濾收集固體沉淀物,用水洗滌,然后用氯仿洗滌。將產(chǎn)物溶于沸水(50毫升)中,用6NHCl處理并冷卻,得到1.43克脒氯嗪。
ENaC; uTPA; polycystin-2(TRPP2)
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).
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.