1346233-68-8

生物活性靶点体外研究体内研究 1346233-68-8 试剂级价格

1346233-68-8

CAS号:1346233-68-8
英文名:3,5-Dichloro-N-[[(1α,5α,6-exo,6α)-3-(3,3-diMethylbutyl)-3-azabicyclo[3.1.0]hex-6-yl]Methyl]-benzaMide
中文名:1346233-68-8
CBNumber:CB52695162
分子式:C19H26Cl2N2O
分子量:369.33
MOL File:1346233-68-8.mol

1346233-68-8化学性质

沸点 :455.5±35.0 °C(Predicted)
密度 :1.184±0.06 g/cm3(Predicted)
储存条件 :2-8°C
溶解度 :DMSO: soluble10mg/mL (clear solution)
酸度系数(pKa) :13.65±0.46(Predicted)
形态 :powder
颜色 :white to beige

安全信息

WGK Germany :3

1346233-68-8性质、用途与生产工艺

生物活性 ML218 是一种有效的，选择性的和口服活性的 T 型 Ca2+ 通道 (Cav3.1，Cav3.2，Cav3.3) 抑制剂，对 Cav3.2 和 Cav3.3 的 IC50 分别为 310 nM 和 270 nM。ML218 抑制丘脑底核 (STN) 神经元的爆发活动。ML218 对 L 或 N 型钙通道，KATP 或 hERG 钾通道无明显抑制作用。ML218 可以穿透血脑屏障。
靶点

IC50: 310 nM (Cav3.2), 270 nM (Cav3.3), and 150 nM (Ca ²⁺ flux)
体外研究

In plasma protein binding studies (equilibrium dialysis), ML218 possesses good free fraction in both rat and human. Intrinsic clearance experiments in liver microsomes indicated that ML218 is highly cleared in rat (CL _int = 115 mL/min/kg), but low to moderately cleared in human liver microsomes (CL _int = 12.7 mL/min/kg).

体内研究

ML218 (0.03-30 mg/kg; oral administration; once; male Sprague-Dawley rats) treatment reverses cataleptic behavior in rats induced by a 0.75 mg/kg dose of haloperidol.
Free brain and plasma concentrations of ML218 increases in a dose proportional manner across the dose range (3 mg/kg: [plasma] = 98 nM, [brain] = 1.66 μM; 10 mg/kg: [plasma] = 282 nM, [brain] = 5.03 μM; 30 mg/kg: 1.2 μM, [brain] = 17.7 μM).
Noncompartmental pharmacokinetic analysis indicates ML218 (1 mg/kg, IV) has a mean residence time (MRT) of nearly 7 h, a value which is consistent with its terminal half-life (t _1/2 = 7 h).

Animal Model:	Male Sprague-Dawley rats (275-299 g) induced by haloperidol
Dosage:	0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg
Administration:	Oral administration; once
Result:	Reversed cataleptic behavior in rats induced by a 0.75 mg/kg dose of haloperidol.