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Preladenant

现货
Catalog No.
A3735
腺苷A2A受体拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,650.00
现货
5mg
¥ 1,500.00
现货
10mg
¥ 2,200.00
现货
25mg
¥ 3,500.00
现货
50mg
¥ 4,850.00
现货

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Background

Preladenant is a high selective antagonist of adenosine A2A receptor with Ki value of 1.1 nM [1].
Parkinson's Disease is characterized by the loss of dopaminergic neuronal projection. The patients with PD lost the capability to control their muscles. As an antagonist of adenosine A2A receptor, preladenant is a non-dopaminergic drug developed for the treatment of PD. This compound showed potency in Phase II clinical trials but failed in Phase III trials and so was discontinued. Preladenant is a methoxyethoxy derivative of the previously discovered A2A receptor antagonist SCH 58261 and has much higher selectivity for A2A receptors over A1 receptors [1 and 2].
Preladenant was obtained through modifying the phenethyl side chain of SCH 58261. It exerted higher binding affinity for both rat and human A2A receptors with Ki values of 2.5 and 1.1 nM, respectively. Preladenant also showed more than 1000-fold higher selectivity for A2A receptors over other adenosine receptors. The Ki values of preladenant for A1, A3 and A2B receptors are all above 1000 nM. Besides that, preladenant showed no significant affinity for a panel of 59 other enzymes, receptors and ion channels. In the cell assays, preladenant also inhibited the activity of both human and rat adenylate cyclase stimulated by CGS 21680 (an agonist of A2A receptor) with Kb values of 1.3 and 0.7 nM, respectively [1].
Preladenant also showed efficacies in animal models. In cynomolgus monkeys treated with MPTP, administration of preladenant at dose of both 1 and 3 mg/kg resulted in parkinsonian scores reduction. In a Dunnets post hoc test, the combination treatment of preladenant and L-Dopa significantly increased the locomotor activity by 80%. Besides that, preladenant was found to have anti- catalepsy effects and dose of 0.3 mg/kg and significantly reduce the hypolocomotion caused by CGS-21680 at dose of 0.1 mg/kg in rats models [2 and 3].
References:
[1] Neustadt B R, Hao J, Lindo N, et al. Potent, selective, and orally active adenosine A 2A receptor antagonists: arylpiperazine derivatives of pyrazolo [4, 3-e]-1, 2, 4-triazolo [1, 5-c] pyrimidines. Bioorganic & medicinal chemistry letters, 2007, 17(5): 1376-1380.
[2] Hodgson R A, Bedard P J, Varty G B, et al. Preladenant, a selective A 2A receptor antagonist, is active in primate models of movement disorders. Experimental neurology, 2010, 225(2): 384-390.
[3] Hodgson R A, Bertorelli R, Varty G B, et al. Characterization of the potent and highly selective A2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2, 4-difluorophenyl]-1-piperazinyl] ethyl]-2-(2-furanyl)-7H-pyrazolo [4, 3-e][1, 2, 4] triazolo [1, 5-c] pyrimidin-5-amine] in rodent models of movement disorders and depression. Journal of Pharmacology and Experimental Therapeutics, 2009, 330(1): 294-303.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt503.56
Cas No.377727-87-2
FormulaC25H29N9O3
SynonymsSCH-420814;SCH 420814;SCH420814
Solubility≥7.3 mg/mL in DMSO, <2.51 mg/mL in EtOH, <2.08 mg/mL in H2O
Chemical Name2-(furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine
SDFDownload SDF
Canonical SMILESNC(N1N=C(C2=CC=CO2)N=C13)=NC4=C3C=NN4CCN5CCN(C(C=C6)=CC=C6OCCOC)CC5
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

原代肌动蛋白GFP小胶质细胞

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月

反应条件

1 μM,15 min

实验结果

使用在Matrigel中生长的原代肌动蛋白GFP小胶质细胞的三维细胞重建来确定响应于Preladenant的细胞分裂,表示为表面积-体积比。在活化的小神经胶质细胞中,浓度为1 μM的Preladenant可防止腺苷诱导的过程回缩。

动物实验[2]:

动物模型

雄性CD 大鼠

剂量

Haloperidol (1 mg/kg s.c.)诱导大鼠的僵住症。在30分钟基线测量后,口服preladenant,并在给药后1小时和4小时重新测试僵住症。

实验结果

Preladenant以剂量依赖性的方式减轻haloperidol给药后1h [F(3,20) = 5.0, p < 0.01]和4h[F(3,20) = 9.8, p < 0.01]的催眠作用,剂量为0.3和1 mg/kg的药物在两个时间点均有显著的统计学效应。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Gyoneva S, Davalos D, Biswas D, et al. Systemic inflammation regulates microglial responses to tissue damage in vivo. Glia, 2014.

[2] Hodgson R A, Bertorelli R, Varty G B, et al. Characterization of the potent and highly selective A2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2, 4-difluorophenyl]-1-piperazinyl] ethyl]-2-(2-furanyl)-7H-pyrazolo [4, 3-e][1, 2, 4] triazolo [1, 5-c] pyrimidin-5-amine] in rodent models of movement disorders and depression. Journal of Pharmacology and Experimental Therapeutics, 2009, 330(1): 294-303.

生物活性

描述 Preladenant(SCH 420814)是一种有效的和选择性的腺苷A2A受体拮抗剂。
靶点 adenosine A2A receptor          
IC50            

质量控制

质量控制和MSDS

批次:

化学结构

Preladenant