| CAS NO: | 1227675-50-4 |
| 包装 | 价格(元) |
| 10mg | 电议 |
| 50mg | 电议 |
| Physical Appearance | Off-white solid |
| Storage | Store at -20°C |
| M.Wt | 368.31 |
| Cas No. | 1227675-50-4 |
| Formula | C17H21N5·2HCl |
| Solubility | <36.83mg/ml in H2O;<36.83mg/ml in DMSO |
| Chemical Name | (R)-1-(2-imino-2,5,6,7-tetrahydro-1H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl)pyrrolidin-3-amine dihydrochloride |
| Canonical SMILES | N[C@]1([H])CCN(C(C2=C(N3)C4=CC=CC=C4CCC2)=NC3=N)C1.Cl.Cl |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 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。溶液形式一般不宜长期储存，请尽快用完。 |
A 943931是一种H4R（组胺受体亚型之一）拮抗剂[1]，对人（Ki = 5 nM）、大鼠（Ki = 4 nM）和小鼠（Kb = 6 nM ）H4Rs具有高亲和性[2]。
H4R是组胺的4种已知的G蛋白偶联受体（H1、H2、H3和H4受体）之一，可介导组胺的生理功能[3]。
HMC-1细胞与300 nM的A 943931孵育20 min可抑制H4R诱导的ALDH2活性增加[4]。在小胶质细胞中，A 943931在10 μM浓度下可部分抑制浓度为0.1 μg/ml的组胺诱导的TNF-α和IL-6释放[5]。在骨髓来源的肥大细胞中，A 943931可抑制组胺诱导的形状变化（IC50 = 0.38 μM）[6]。
在小鼠中，A 943931在33 μmol/kg剂量下腹腔给药可有效抑制H4R激活剂诱导的发痒[6]。在多个临床前模型中，H4R与炎症有关[7]。在多个物种的体外和体内试验中，A 943931具有优异的拮抗活性，并有良好的口服生物利用度（90%）和优异的代谢稳定性。该物质在大鼠疼痛模型中具有良好疗效，在小鼠中是一种良好的抗炎药剂[8]。在大鼠体内，A 943931的口服生物利用度为34%，半衰期为2.6 h[2]。A 943931可在退缩模型中有效减弱福尔马林诱导的急性炎性疼痛，在大鼠机械和热痛觉过敏模型中可减弱卡拉胶诱导的急性炎性疼痛[9]。
参考文献：
[1]. Erich H. Schneider and Roland Seifert. The histamine H4-receptor and the central and peripheral nervous system: A critical analysis of the literature. Neuropharmacology, 2015, xxx:1-13.
[2]. Rogier A. Smits, Herman D. Lim, Tiffany van der Meer, et al. Ligand based design of novel histamine H4 receptor antagonists; fragment optimization and analysis of binding kinetics. Bioorg. Med. Chem. Lett., 2012, 22: 461-467.
[3]. Huaqing Liu, Robert J. Altenbach, Tracy L. Carr, et al. cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), A New Histamine H4R Antagonist that Blocks Pain Responses against Carrageenan-Induced Hyperalgesia. J. Med. Chem., 2008, 51:7094-7098.
[4]. Silvia Aldi, Ken-ichi Takano, Kengo Tomita, et al. Histamine H4-Receptors Inhibit Mast Cell Renin Release in Ischemia/Reperfusion via PKCε-Dependent Aldehyde Dehydrogenase Type-2 Activation. J. Pharmacol. Exp. Ther., 2014, 349(3):508-17.
[5]. Jin Zhu, Chen Qu, Xiang Lu, et al. Activation of Microglia by Histamine and Substance P. Cell Physiol. Biochem., 2014, 34(3):768-80.
[6]. Harald Engelhardt, Rogier A Smits, Rob Leurs, et al. A new generation of anti-histamines: Histamine H4 receptor antagonists on their way to the clinic. Curr. Opin. Drug Discov. Devel., 2009, 12(5):628-43.
[7]. Jeffery M Cowden, Fuqu Yu, Homayon Banie, et al. The histamine H4 receptor mediates inflammation and Th17 responses in preclinical models of arthritis. Ann. Rheum. Dis., 2014, 73:600-608.
[8]. Rob Leurs, Paul L Chazot, Fiona C Shenton, et al. Molecular and biochemical pharmacology of the histamine H4 receptor. British Journal of Pharmacology, 2009, 157: 14-23.
[9]. David Burns, Niu Shin, Ravi Jalluri, et al. Annual Reports in Medicinal Chemistry: H4 Receptor Antagonists and Their Potential Therapeutic Applications. Burlington: Academic Press, 2014.
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