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873697-71-3

中文名稱 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
英文名稱 OMecaMtiv Mecarbil
CAS 873697-71-3
分子式 C20H24FN5O3
MDL 編號 MFCD18633260
分子量 401.435
MOL 文件 873697-71-3.mol
更新日期 2024/10/24 19:15:53
873697-71-3 結(jié)構(gòu)式 873697-71-3 結(jié)構(gòu)式

基本信息

中文別名
OMECAMTIV MECARBIL (CK-1827452)
CK1827452
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
英文別名
CK1827452
CK-1827452
CK 1827452O
mecamtiv mecarbil
OMecaMtiv Mecarbil
OMecaMtiv Mecarbil (CK-1827452)
CK-1827452 (OMecaMtiv Mecarbil)
methyl 4-(2-fluoro-3-(3-(6-methylpyridin-3-yl)ureido)benzyl)piperazine-1-carboxylate
Methyl 4-[[2-fluoro-3-[N'-(6-methylpyridin-3-yl)ureido]phenyl]methyl]piperazine-1-carboxylate
methyl 4-[(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}phenyl)methyl] piperazine-1-carboxylate
所屬類別
生物化工:ATPase 激活劑

物理化學(xué)性質(zhì)

熔點(diǎn)180℃
儲存條件-20°C冷凍
溶解度可溶于DMSO(少許)、甲醇(少許)
形態(tài)固體
顏色白色至灰白色
水溶解性40.25mg/L at 25℃
LogP-0.531

安全數(shù)據(jù)

危險性符號(GHS)GHS hazard pictograms
GHS08
警示詞危險
危險性描述H372-H370

常見問題列表

生物活性
Omecamtiv mecarbil (CK-1827452)是一種特異性的心肌肌球蛋白激動劑,是用于左心室收縮性心臟衰竭的臨床藥物。Phase 2。
體外研究
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.
體內(nèi)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.
靶點(diǎn)
TargetValue
Myosin ATPase
體外研究

在體外,Omecamtiv mecarbil通過增加肌球蛋白ATPase比率,選擇性激活心肌肌球蛋白。 在離體心肌細(xì)胞中,Omecamtiv mecarbil導(dǎo)致肌細(xì)胞收縮性增加,并使肌漿球蛋白抑制劑BDM失效,而不增加鈣轉(zhuǎn)運(yùn)或抑制PDE通路。

體內(nèi)研究
在SD大鼠,深水動物和心臟衰竭大鼠體內(nèi),Omecamtiv mecarbil在血漿中濃度達(dá)到0.4 mM后顯著增加縮短分?jǐn)?shù)。在清醒狀態(tài)下心肌梗死(MI-sHF)的狗體內(nèi),Omecamtiv mecarbil顯著增加壁室厚度(25%),每搏輸出量(44%),心輸出量(22%)和左心室 (LV) 收縮射血時間(26%)。此外,Omecamtiv mecarbil也會導(dǎo)致一些血流動力學(xué)參數(shù),包括心率,平均左房壓,和LV末期舒張壓下降。在左心室肥大(LVH-sHF)的清醒的狗體內(nèi),Omecamtiv mecarbil對血流動力學(xué)參數(shù)具有類似且統(tǒng)計學(xué)差異化的影響。
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