AM0902

中文名称:

AM0902

中文同义词:

英文名称:

AM-0902

英文同义词:

AM0902;AM-0902;1-[[3-[2-(4-chlorophenyl)ethyl]-1,2,4-oxadiazol-5-yl]methyl]-7-methylpurin-6-one;1-[[3-[2-(4-Chlorophenyl)ethyl]-1,2,4-oxadiazol-5-yl]methyl]-1,7-dihydro-7-methyl-6H-purin-6-one;CS-2717;AM-0902 (AM 0902;6H-Purin-6-one, 1-[[3-[2-(4-chlorophenyl)ethyl]-1,2,4-oxadiazol-5-yl]methyl]-1,7-dihydro-7-methyl-;1-({3-[2-(4-Chlorophenyl)ethyl]-1,2,4-oxadiazol-5-yl}methyl)-7-methyl-1,7-dihydro-6H-purin-6-one

CAS号:

1883711-97-4

分子式:

C17H15ClN6O2

分子量:

370.79

EINECS号:

相关类别:

API

Mol文件:

1883711-97-4.mol

沸点 

657.3±65.0 °C(Predicted)

密度 

1.51±0.1 g/cm3(Predicted)

储存条件 

Sealed in dry,2-8°C

酸度系数(pKa)

2.36±0.50(Predicted)

生物活性

AM-0902 是一种有效的选择性瞬时受体电位 A1 (TRPA1) 拮抗剂，作用于 rTRPA1 和 hTRPA1 的 IC50 值分别为 71 和 131 nM。

靶点

IC50: 71 nM (rTRPA1), 131 nM (hTRPA1)

体外研究

AM-0902 is a potent, selective antagonist of TRPA1 with IC 50 s of 71 and 131 nM for rTRPA1 and hTRPA1, respectively. AM-0902 is highly permeable (average P app =44.5 μcm/s in MDCK cells), an unlikely substrate for P-gp (efflux ratio=1.3 in P-gp overexpressing MDCK cells), and demonstrates good solubility (PBS pH 7.4: 226 μM, SIF: 248 μM). AM-0902 shows good selectivity over other TRP channels, as no activity is observed against human TRPV1 or TRPV4, or rat TRPV1, TRPV3, or TRPM8, at concentrations up to 10 μM. AM-0902 inhibits 45 Ca 2+ flux upon activation of rat TRPA1 with methylglyoxal with an IC 50 of 0.019 μM.

体内研究

AM-0902 is a potent, selective antagonist of TRPA1 in vivo. AM-0902 has moderate terminal elimination half-life (t 1/2 =0.6 h and 2.8 h for rat (0.5 mg/kg, iv), rat (30 mg/kg, oral)). A dose-dependent reduction of allyl isothiocyanate (AITC)-induced flinching is observed for AM-0902, with a significant reduction in flinching observed postdosing of 10 and 30 mg/kg. The unbound plasma concentrations (C u ) at 1 h for the 1, 3, 10, and 30 mg/kg doses are 0.051±0.024 (n=8), 0.19±0.11 (n=8), 0.58±0.35 (n=8), and 2.2±0.40 (n=8) μM, covering the in vitro rat TRPA1 45 Ca 2+ IC 50 at 0.72, 2.7, 8.2, and 30.3 fold, respectively. A good exposure-response relationship is observed in this target coverage model. An unbound in vivo IC 50 of 0.35 μM, which is in good agreement with the in vitro rat TRPA1 45 Ca 2+ IC 50 , and unbound in vivo IC 90 of 1.7 μM are determined. It is noteworthy that at a dose of 30 mg/kg, AM-0902 engages TRPA1 at concentrations that exceed the in vivo IC 90 , making it a useful tool for exploration of in vivo models of acute pain.