A-804598游离态 | 1125758-85-1

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: A-804598游离态
• 中文别名: N-氰基-N”-[((1S)-1-苯乙基]-N'-5-喹啉基-胍
• 英文名称: A-804598
• 英文别名: N-cyano-N''-[(1s)-1-phenylethyl]-N'-5-quinolinyl-guanidine；1-cyano-2-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine
• CAS: 1125758-85-1
• 化学式: C₁₉H₁₇N₅
• 分子量: 315.377
• InChiKey: PQYCRDPLPKGSME-AWEZNQCLSA-N

物化性质

• 沸点：
  498.0±47.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶10mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  73.1
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

A-804598 是一个 CNS 渗透，竞争性和选择性的 P2X7 受体拮抗剂，作用于小鼠，大鼠和人的 P2X7 受体，IC50s 分别是 9 nM, 10 nM 和 11 nM。

靶点

IC50: 9 nM (mouse P2X7 receptor), 10 nM (rat P2X7 receptor), 11 nM (human P2X7 receptor)

体外研究

Pre-incubation with A-804598 (0.1-10 μM; 1 hour) significantly attenuates BzATP-induced cell loss in a concentration-dependent manner. 3 μM A-804598 exhibits the greatest protective effect against BzATP-induced cytotoxicity.

Cell Cytotoxicity Assay

Cell Line:	microglial cell
Concentration:	0.1, 0.3, 1, 3, 10 μM
Incubation Time:	1 hour
Result:	Protected against BzATP-induced cytotoxicity in both inactivated and activated microglia.

体内研究

A chroni treatment with A-804598 (intraperitoneal injection; 30 mg/kg; five times a week) decreases the expression of LC3B-II and SQSTM1/p62 in lumbar spinal cord at end stage of disease.

Animal Model:	Adult B6.Cg-Tg (SOD1-G93A) 1Gur/J female mice
Dosage:	30 mg/kg
Administration:	Intraperitoneal injection; five times a week
Result:	Decreased SQSTM1/p62 expression.

反应信息

• 作为产物：
  描述：

  5-氨基喹啉 以 异丙醇 、 乙腈 为溶剂， 反应 65.0h， 生成 A-804598游离态
  参考文献：
  名称：

  Discovery and pharmacological evaluation of a novel series of adamantyl cyanoguanidines as P2X7 receptor antagonists

  摘要：

  Here we report adamantyl cyanoguanidine compounds based on hybrids of the adamantyl amide scaffold reported by AstraZeneca and cyanoguanidine scaffold reported by Abbott Laboratories. Compound 27 displayed five-fold greater inhibitory potency than the lead compound 2 in both pore-formation and interleukin-1 beta release assays, while 35-treated mice displayed an antidepressant phenotype in behavioral studies. This SAR study provides a proof of concept for hybrid compounds, which will help in the further development of P2X(7)R antagonists. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.060