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189362-06-9

中文名稱 189362-06-9
英文名稱 K134
CAS 189362-06-9
分子式 C22H29N3O4
分子量 399.48
MOL 文件 189362-06-9.mol
189362-06-9 結(jié)構(gòu)式 189362-06-9 結(jié)構(gòu)式

基本信息

中文別名
化合物 T15640
英文別名
K134
OPC33509
1-Cyclopropyl-1-((1R,2R)-2-hydroxycyclohexyl)-3-(3-((2-oxo-1,2-dihydroquinolin-6-yl)oxy)propyl)urea
Urea, N-cyclopropyl-N'-[3-[(1,2-dihydro-2-oxo-6-quinolinyl)oxy]propyl]-N-[(1R,2R)-2-hydroxycyclohexyl]-

物理化學(xué)性質(zhì)

沸點(diǎn)731.4±60.0 °C(Predicted)
密度1.29±0.1 g/cm3(Predicted)
儲(chǔ)存條件4°C, away from moisture and light
溶解度溶于二甲基亞砜
酸度系數(shù)(pKa)11.13±0.70(Predicted)
形態(tài)Solid
顏色White to off-white

常見問(wèn)題列表

生物活性
K134 是一種磷酸二酯酶 3 (PDE3) 抑制劑。抑制 PDE3A,PDE3B,PDE5, PDE2,PDE4 和 IC50 分別為0.1,0.28,12.1,>300 和 >300 μM。
靶點(diǎn)

IC50: 0.1 μM (PDE3A), 0.28 μM (PDE3B), 12.1 μM (PDE5)

體外研究

K134 (K-134) inhibits rat platelet aggregation induced by collagen and ADP in a dose-dependent manner in vitro. The half-maximal (50%) inhibitory concentration (IC 50 ) values of K134 are 2.5 μM and 3.2 μM, respectively. In vitro experiments, K134 also inhibits mouse platelet aggregation induced by collagen and ADP in a dose-dependent manner, and the IC 50 s are 5.5 μM and 6.7 μM, respectively.

體內(nèi)研究

K134 (K-134) significantly prolongs middle cerebral artery (MCA) occlusion time at doses >10 mg/kg, and reduces cerebral infarct size at 30 mg/kg in the stroke model (n?=?12, 87.5±5.6 vs. 126.8±7.5 mm 3 , P<0.01), indicating its potent antithrombotic effect. The overall bleeding risk of K134 is assessed in general in mice. Single oral administration of K134 does not prolong bleeding time at a dose of 30 mg/kg compared to control (106±5 vs. 110±5 s, not significant). Moreover, a sufficiently high enough plasma concentration of K134 (13.6±2.3 μM) is detected to inhibit platelet aggregation at 10 min after single administration in mice at a dose of 30 mg/kg, which is the same time point as the above test of bleeding time. Next, the effects of PDE3 inhibitors on thrombus formation are also investigated in an arteriovenous shunt model in rats. K134 significantly reduces the incidence of occlusive shunt thrombi at doses above 10 mg/kg (half-maximal effective dose: ED 50 =11 mg/kg). The plasma concentration of K134 is 0.43±0.08 μM (C max ) at a dose of 10 mg/kg.

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