中文名称:
N-[2-[2-(二甲基氨基)乙氧基]-4-(1H-吡唑-4-基)苯基]-2,3-二氢-1,4-苯并二恶烷-2-甲酰胺
中文同义词:
N-[2-[2-(二甲基氨基)乙氧基]-4-(1H-吡唑-4-基)苯基]-2,3-二氢-1,4-苯并二恶烷-2-甲酰胺;ROCK-II抑制剂(SR-3677)
英文名称:
N-[2-[2-(Dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-1,4-benzodioxin-2-carboxamide
英文同义词:
SR3677;N-[2-[2-(Dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl-2,3-dihydro-1,4-benzodioxin-2-carboxamidehydrochloride;SR 3677 hydrochloride;N-(2-(2-(diMethylaMino)ethoxy)-4-(1H-pyrazol-4-yl)phenyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carboxaMide;SR 3677 dihydrochloride;N-(2-(2-(Dimethylamino)ethoxy)-4-(1H-pyrazol-4-yl)phenyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-ca;N-[2-[2-(Dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-benzo[b][1,4]dioxin-2-carboxamide;N-[2-[2-(Dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-1,4-benzodioxin-2-carboxamide
沸点
646.9±55.0 °C(Predicted)
溶解度
DMSO: soluble15mg/mL, clear
酸度系数(pKa)
11.90±0.70(Predicted)
生物活性
SR-3677是高效的选择性的ROCK-II抑制剂，IC50值为~3 nM。
靶点
ROCK-II
3 nM (IC 50 )
ROCK-I
56 nM (IC 50 )
ROCK-II
3 nM (IC 50 )
ROCK-I
56 nM (IC 50 )
体外研究
SR-3677 has an IC 50 of ~3 nM in enzyme and cell based assays and has an off-target hit rate of 1.4% against 353 kinases, and inhibits only 3 out of 70 nonkinase enzymes and receptors. The IC 50 value of SR-3677 for ROCK-I is 56±12 nM. The hydrophobic interaction of the benzodioxane phenyl ring with the hydrophobic surface of the pocket is the dominating factor that contributes to the high potency of SR-3677.
体内研究
ExVivo: Pharmacology studies shows that SR-3677 is efficacious in both, increasing ex vivo aqueous humor outflow in porcine eyes and inhibiting myosin light chain phosphorylation. Continuous exposure of 25 µM SR-3677 increases the outflow facility by 60% at 1 h perfusion, increasing to 70–80% for the 2–5 h time points.
