sodium 1-amino-4-[4-([1,3]diazine-2-ylamino)phenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate | 1052089-26-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: sodium 1-amino-4-[4-([1,3]diazine-2-ylamino)phenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate
• 英文别名: Sodium;1-amino-9,10-dioxo-4-[4-(pyrimidin-2-ylamino)anilino]anthracene-2-sulfonate
• CAS: 1052089-26-5
• 化学式: C₂₄H₁₆N₅O₅S*Na
• 分子量: 509.477
• InChiKey: DHSXKIJRVYLSCI-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.23
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  176
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  对苯二胺 在 铜 作用下， 以 水 、 丙酮 为溶剂， 生成 sodium 1-amino-4-[4-([1,3]diazine-2-ylamino)phenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate
  参考文献：
  名称：

  Discovery of Potent Competitive Antagonists and Positive Modulators of the P2X2 Receptor

  摘要：

  Evaluation and optimization of anthraquinone derivatives related to Reactive Blue 2 at P2X2 receptors yielded the first potent and selective P2X2 receptor antagonists. The compounds were tested for inhibition of ATP (10 mu M) mediated currents in Xenopus oocytes expressing the rat P2X2 receptor. The most potent antagonists were sodium 1-amino-4-[3-(4,6-dichloro[1,3,5]triazine-2-ylamino)phenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (63, PSB-10211, IC50 86 nM) and disodium 1-amino-4-[3-(4,6-dichloro[1,3,5]triazine-2-ylamino)-4-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (57, PSB-1011, IC50 79 nM). Compound 57 exhibited a competitive mechanism of action (pA(2) 7.49). It was > 100-fold selective versus P2X4, P2X7, and several investigated P2Y receptor sub-types (P2Y(2,4,6,12)); selectivity versus P2X1 and P2X3 receptors was moderate ( > 5-fold). Compound 57 was > 13-fold more potent at the homomeric P2X2 than at the heteromeric P2X2/3 receptor. Several anthraquinone derivatives were found to act as positive modulators of ATP effects at P2X2 receptors, for example, sodium 1-amino-4-(3-phenoxyphenylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (51, PSB-10129, EC50 489 nM), which led to about a 3-fold increase in the ATP-elicited current.

  DOI：

  10.1021/jm1012193

文献信息

• High-Affinity, Non-Nucleotide-Derived Competitive Antagonists of Platelet P2Y₁₂ Receptors
  作者：Younis Baqi、Kerstin Atzler、Meryem Köse、Markus Glänzel、Christa E. Müller

  DOI：10.1021/jm9003297

  日期：2009.6.25

  Anthraquinone derivatives related to the moderately potent, nonselective P2Y(12) receptor antagonist reactive blue 2 (6) have been synthesized and optimized with respect to P2Y(12) receptor affinity. A radioligand binding assay utilizing human blood platelet membranes and the P2Y(12) receptor-selective antagonist radioligand [H-3]2-propylthioadenosine-5'-adenylic acid (1,1-dichloro-1-phosphonomethyl-1-phosphonyl) anhydride ([H-3]PSB-0413) was applied for compound testing. 1-Amino-2-sulfoanthraquinone derivatives bearing a (p-phenylamino)anilino substitution in the 4-position and an additional acidic function in the meta-position of the aniline ring showed high P2Y(12) receptor affinity. These new anthraquinone derivatives became accessible by a recently developed copper(0)-catalyzed Ullmann coupling reaction of 1-amino-4-bromoanthraquinone derivatives with anilines in phosphate buffer under microwave irradiation. The most potent compounds exhibited K-i values of 24.9 nM (1-amino-4-[4-phenylamino-3-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, PSB-0739, 39), and 2 1.0 nM (1-amino-4-[4-phenylamino-3-carboxyphenylamino]- 9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, PSB-0702, 41), respectively. 1-Amino-2-sulfo-4-anilinoanthraquinone derivatives appeared to be noncytotoxic, as shown for selected derivatives at two human cell lines (melanoma and astrocytoma). Compounds 39 and 41 represent new lead structures for the development of antithrombotic drugs.
• Discovery of Potent Competitive Antagonists and Positive Modulators of the P2X2 Receptor
  作者：Younis Baqi、Ralf Hausmann、Christiane Rosefort、Jürgen Rettinger、Günther Schmalzing、Christa E. Müller

  DOI：10.1021/jm1012193

  日期：2011.2.10

  Evaluation and optimization of anthraquinone derivatives related to Reactive Blue 2 at P2X2 receptors yielded the first potent and selective P2X2 receptor antagonists. The compounds were tested for inhibition of ATP (10 mu M) mediated currents in Xenopus oocytes expressing the rat P2X2 receptor. The most potent antagonists were sodium 1-amino-4-[3-(4,6-dichloro[1,3,5]triazine-2-ylamino)phenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (63, PSB-10211, IC50 86 nM) and disodium 1-amino-4-[3-(4,6-dichloro[1,3,5]triazine-2-ylamino)-4-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (57, PSB-1011, IC50 79 nM). Compound 57 exhibited a competitive mechanism of action (pA(2) 7.49). It was > 100-fold selective versus P2X4, P2X7, and several investigated P2Y receptor sub-types (P2Y(2,4,6,12)); selectivity versus P2X1 and P2X3 receptors was moderate ( > 5-fold). Compound 57 was > 13-fold more potent at the homomeric P2X2 than at the heteromeric P2X2/3 receptor. Several anthraquinone derivatives were found to act as positive modulators of ATP effects at P2X2 receptors, for example, sodium 1-amino-4-(3-phenoxyphenylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (51, PSB-10129, EC50 489 nM), which led to about a 3-fold increase in the ATP-elicited current.