产品
编 号：F718969
分子式：C20H21N7O
分子量：375.43
分子式：C20H21N7O
分子量：375.43
产品类型
规格
价格
是否有货
结构图
CAS No: 875898-41-2
产品详情
生物活性：
NMDA receptor antagonist 2 is a potent and orally active NR2B subtype-selective NMDA antagonist with an IC50 and a Ki of 1.0 nM and 0.88 nM, respectively. NMDA receptor antagonist 2 is used for the study of neuropathic pain and Parkinson’s disease.
体内研究：
In pharmacokinetic studies with higher species, NMDA receptor antagonist 2 shows excellent oral bioavailability (F=83%), half-life (T1/2=7.5 hours) and clearance (CL=3.6 mL/min/kg) in dog. And it exhibits moderate clearance (CL=12 mL/min/kg) and oral bioavailability (F=17%) in rhesus, the half-life (T1/2) is 1.5 hours.In a rat pharmacokinetic study, NMDA receptor antagonist 2 shows oral bioavailability (F=23 %), half-life (T1/2=0.7 hours) and clearance (CL=24 mL/min/kg), the receptor occupancy ED50 with oral administration is 4.8 mg/kg in rat.In the spinal nerve ligation model of neuropathic pain in rats, surgical ligation of two lumbar nerves in the spinal column induces a state of mechanical allodynia.NMDA receptor antagonist 2 (oral administration; 3-30 mg/kg) inhibits tactile allodynia in a dose-dependent manner after oral administration at 10 and 30 mg/kg. It produces an average improvement in the maximal possible effect of 15% (3 mg/kg), 41% (10 mg/kg), and 69% (30 mg/kg) compared to vehicle treated animals.NMDA receptor antagonist 2 (oral administration; 3-30 mg/kg) is efficacious in an acute rodent model of Parkinson’s disease. Haloperidol (HY-14538) is administered at a dose previously shown to elicit an acute cataleptic response in rats, compound 22 reduces catalepsy scores in a dose-dependent manner, producing average improvements of 34% (3 mg/kg), 86% (10 mg/kg), and 92% (30 mg/kg) when it compares to vehicle group.
体外研究：
NMDA receptor antagonist 2 leads to excellent potency at NR2B (Ki=0.88 nM) and selectivity over hERG binding (IP=20000 nM). NMDA receptor antagonist 2 is evaluated in a functional assay measuring Ca2+?flux in cells expressing recombinant NR1/NR2B receptors. Selectivity over the hERG-channel is evaluated in an MK-499-binding assay.NMDA receptor antagonist 2 is highly potent in a functional assay using cells expressing NR2B (IC50=1.0 nM) and remains equipotent in a binding assay using a sample of homogenized human temporal cortex (Ki=0.81 nM). In an electrophysiology assay using NR2B receptors,?Compound 22?shows full blockade of ion flux with?KD=0.35 nM. Compound?22?also exhibits high levels of selectivity over NR2A (IC50=200 μM), hERG binding (IP=20 μM), α-adrenergic receptors based on Prazosin binding (IC50>100 μM),?and CYP P450s including CYP3A4, 2C9, and 2D6.
NMDA receptor antagonist 2 is a potent and orally active NR2B subtype-selective NMDA antagonist with an IC50 and a Ki of 1.0 nM and 0.88 nM, respectively. NMDA receptor antagonist 2 is used for the study of neuropathic pain and Parkinson’s disease.
体内研究：
In pharmacokinetic studies with higher species, NMDA receptor antagonist 2 shows excellent oral bioavailability (F=83%), half-life (T1/2=7.5 hours) and clearance (CL=3.6 mL/min/kg) in dog. And it exhibits moderate clearance (CL=12 mL/min/kg) and oral bioavailability (F=17%) in rhesus, the half-life (T1/2) is 1.5 hours.In a rat pharmacokinetic study, NMDA receptor antagonist 2 shows oral bioavailability (F=23 %), half-life (T1/2=0.7 hours) and clearance (CL=24 mL/min/kg), the receptor occupancy ED50 with oral administration is 4.8 mg/kg in rat.In the spinal nerve ligation model of neuropathic pain in rats, surgical ligation of two lumbar nerves in the spinal column induces a state of mechanical allodynia.NMDA receptor antagonist 2 (oral administration; 3-30 mg/kg) inhibits tactile allodynia in a dose-dependent manner after oral administration at 10 and 30 mg/kg. It produces an average improvement in the maximal possible effect of 15% (3 mg/kg), 41% (10 mg/kg), and 69% (30 mg/kg) compared to vehicle treated animals.NMDA receptor antagonist 2 (oral administration; 3-30 mg/kg) is efficacious in an acute rodent model of Parkinson’s disease. Haloperidol (HY-14538) is administered at a dose previously shown to elicit an acute cataleptic response in rats, compound 22 reduces catalepsy scores in a dose-dependent manner, producing average improvements of 34% (3 mg/kg), 86% (10 mg/kg), and 92% (30 mg/kg) when it compares to vehicle group.
体外研究：
NMDA receptor antagonist 2 leads to excellent potency at NR2B (Ki=0.88 nM) and selectivity over hERG binding (IP=20000 nM). NMDA receptor antagonist 2 is evaluated in a functional assay measuring Ca2+?flux in cells expressing recombinant NR1/NR2B receptors. Selectivity over the hERG-channel is evaluated in an MK-499-binding assay.NMDA receptor antagonist 2 is highly potent in a functional assay using cells expressing NR2B (IC50=1.0 nM) and remains equipotent in a binding assay using a sample of homogenized human temporal cortex (Ki=0.81 nM). In an electrophysiology assay using NR2B receptors,?Compound 22?shows full blockade of ion flux with?KD=0.35 nM. Compound?22?also exhibits high levels of selectivity over NR2A (IC50=200 μM), hERG binding (IP=20 μM), α-adrenergic receptors based on Prazosin binding (IC50>100 μM),?and CYP P450s including CYP3A4, 2C9, and 2D6.
产品资料
Copyright©2015-2024 沪ICP备2022026524号-1
沪公网安备