4-[[2-氟-3-[N'-(6-甲基吡啶-3-基)脲基]苯基]甲基]哌嗪-1-羧酸甲酯

生物活性体外研究体内研究生物活性靶点体外研究体内研究 4-[[2-氟-3-[N'-(6-甲基吡啶-3-基)脲基]苯基]甲基]哌嗪-1-羧酸甲酯试剂级价格

CAS号:873697-71-3
英文名:OMecaMtiv Mecarbil
中文名:4-[[2-氟-3-[N'-(6-甲基吡啶-3-基)脲基]苯基]甲基]哌嗪-1-羧酸甲酯
CBNumber:CB92561487
分子式:C20H24FN5O3
分子量:401.43
MOL File:873697-71-3.mol

4-[[2-氟-3-[N'-(6-甲基吡啶-3-基)脲基]苯基]甲基]哌嗪-1-羧酸甲酯化学性质

熔点 :180℃
储存条件 :-20°C Freezer
溶解度 :DMSO (Slightly), Methanol (Slightly)
形态 :Solid
颜色 :White to Off-White
水溶解性 :40.25mg/L at 25℃
LogP :-0.531

4-[[2-氟-3-[N'-(6-甲基吡啶-3-基)脲基]苯基]甲基]哌嗪-1-羧酸甲酯性质、用途与生产工艺

生物活性 Omecamtiv mecarbil (CK-1827452)是一种特异性的心肌肌球蛋白激动剂，是用于左心室收缩性心脏衰竭的临床药物。Phase 2。
体外研究 In vitro, Omecamtiv mecarbil selectively activates cardiac myosin by increasing the myosin ATPase rate. In isolated cardiac myocytes, Omecamtiv mecarbil results in increase of myocyte contractility and overcomes of the myosin inhibitor BDM without increasing the calcium transient or inhibiting the PDE pathway.
体内研究 Omecamtiv mecarbil significantly increases fractional shortening starting at 0.4 mM plasma concentrations in SD rats, sham animals and in rats with heart failure. In conscious dogs with myocardial infarction (MI-sHF), Omecamtiv mecarbil leads to a significant increase in wall thickening (25%), stroke volume (44%), cardiac output (22%) and left ventricular (LV) systolic ejection time (26%). In addition, Omecamtiv mecarbil also results in the decreases of some hemodynamic parameters including heart rate, mean left atrial pressure, and LV end-diastolic pressure. In conscious dogs with left ventricular hypertrophy (LVH-sHF), Omecamtiv mecarbil leads to similar and not statistically different effects on hemodynamic parameters.
生物活性 Omecamtiv mecarbil (CK-1827452)是一种特异性的心肌肌球蛋白激动剂，是用于左心室收缩性心脏衰竭的临床药物。Phase 2。
靶点
Target Value
Myosin ATPase
体外研究
在体外，Omecamtiv mecarbil通过增加肌球蛋白ATPase比率，选择性激活心肌肌球蛋白。在离体心肌细胞中，Omecamtiv mecarbil导致肌细胞收缩性增加，并使肌浆球蛋白抑制剂BDM失效，而不增加钙转运或抑制PDE通路。
体内研究在SD大鼠，深水动物和心脏衰竭大鼠体内，Omecamtiv mecarbil在血浆中浓度达到0.4 mM后显著增加缩短分数。在清醒状态下心肌梗死(MI-sHF)的狗体内，Omecamtiv mecarbil显著增加壁室厚度(25%)，每搏输出量(44%)，心输出量(22%)和左心室 (LV) 收缩射血时间(26%)。此外，Omecamtiv mecarbil也会导致一些血流动力学参数，包括心率，平均左房压，和LV末期舒张压下降。在左心室肥大(LVH-sHF)的清醒的狗体内，Omecamtiv mecarbil对血流动力学参数具有类似且统计学差异化的影响。