sodium 1-amino-4-((4-aminophenyl)amino)-9,10-dioxo-9,10 dihydroanthracene-2-sulfonate | 40951-76-6

• 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-aminophenyl)amino)-9,10-dioxo-9,10 dihydroanthracene-2-sulfonate
• 英文别名: sodium 1-amino-4-((4-aminophenyl)amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate；sodium 1-amino-4-(4-aminophenylamino)-9,10-dioxo-9,10-dihydroanthracene 2-sulfonate；sodium 1-amino-4-(4-aminophenylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate；sodium 1-amino-4-[(4-aminophenyl)amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulfonate；sodium 1-amino-4-(4-aminophenylaniino)-9,10-dioxo-9,10-dihydroanthracene 2-sulfonate；Sodium;1-amino-4-(4-aminoanilino)-9,10-dioxoanthracene-2-sulfonate
• CAS: 40951-76-6
• 化学式: C₂₀H₁₄N₃O₅S*Na
• 分子量: 431.404
• InChiKey: BRJFZCXWKYXAOE-UHFFFAOYSA-M

物化性质

• 熔点：
  >300 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -0.72
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  164
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  sodium 1-amino-4-((4-aminophenyl)amino)-9,10-dioxo-9,10 dihydroanthracene-2-sulfonate 在 水 、 sodium carbonate 作用下， 以 水 、 丙酮 为溶剂， 反应 1.0h， 生成 sodium 1-amino-4-[4-(4,6-dihydroxy[1,3,5]triazine-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
• 作为产物：
  描述：

  sodium 1-amino-4-bromoanthraquinone-2-sulfonate 、 对苯二胺 在 铜 作用下， 以 aq. phosphate buffer 为溶剂， 以53%的产率得到sodium 1-amino-4-((4-aminophenyl)amino)-9,10-dioxo-9,10 dihydroanthracene-2-sulfonate
  参考文献：
  名称：

  1-氨基-4-(苯基氨基)蒽醌-2-磺酸钠衍生物作为RANKL诱导的破骨细胞生成的新型抑制剂的开发

  摘要：

  合成了一系列 1-氨基-4-（苯基氨基）蒽醌-2-磺酸钠衍生物，并使用 TRAP 染色试验评估了对破骨细胞的抑制作用。其中，两种化合物 LCCY-13 和 LCCY-15 剂量依赖性地抑制核因子-κB 配体（RANKL）诱导的破骨细胞形成的受体激活剂。此外，对 RAW264.7 细胞的细胞毒性试验表明，这些化合物对破骨细胞骨吸收的抑制不是它们的细胞毒性的结果。此外，通过使用免疫荧光分析包括对细胞核中 NFATc1 表达水平的特异性抑制，进一步证实了化合物 LCCY-13 和 LCCY-15 的抑制活性。此外，根据凹坑形成试验，LCCY-13 和 LCCY-15 还显着减弱了破骨细胞的骨吸收活性。因此，

  DOI：

  10.1002/ardp.201500475

文献信息

• Rapid and Efficient Microwave-Assisted Copper(0)-Catalyzed Ullmann Coupling Reaction:  General Access to Anilinoanthraquinone Derivatives
  作者：Younis Baqi、Christa E. Müller

  DOI：10.1021/ol070102v

  日期：2007.3.1

  reaction of bromaminic acid (1) with aniline derivatives 2a-z in phosphate buffer. Good to excellent isolated yields were obtained within only 2-20 min at 80-120 degrees C and 40-100 W. The new procedure provides the first general access to anilinoanthraquinones, furnishing a number of previously inaccessible compounds. It is superior to classical methods in all aspects, including yields, reaction time

  [结构：见文字]。苯胺蒽醌3a-z的合成是通过新的Cu（0）催化的溴酸（1）与苯胺衍生物2a-z在磷酸盐缓冲液中的微波辅助的Ullmann偶联反应完成的。在80-120摄氏度和40-100 W下仅需2-20分钟即可获得良好至优异的分离收率。新方法首次提供了苯胺基蒽醌的通用途径，从而提供了许多以前无法获得的化合物。它在所有方面都比传统方法优越，包括产率，反应时间和多功能性。
• NOVEL P2Y12 RECEPTOR ANTAGONISTS
  申请人：Müller Christa E.

  公开号：US20100210654A1

  公开（公告）日：2010-08-19

  The present invention relates to novel P2Y 12 receptor antagonists useful for treating, alleviating and/or preventing diseases and disorders related to P2Y 12 receptor function as well as pharmaceutical compositions comprising such compounds and methods for preparing such compounds. The present invention is further directed to the use of these compounds, alone or in combination with other therapeutic agents, for the alleviation, prevention and/or treatment of diseases and disorders, especially the use as antithrombotic agents for inhibiting platelet aggregation.

  本发明涉及一种新的P2Y12受体拮抗剂，可用于治疗、缓解和/或预防与P2Y12受体功能相关的疾病和障碍，以及包含这些化合物的制药组合物和制备这些化合物的方法。本发明进一步涉及使用这些化合物，单独或与其他治疗剂联合使用，以缓解、预防和/或治疗疾病和障碍，特别是用作抗血栓药物来抑制血小板聚集。
• Development of Anthraquinone Derivatives as Ectonucleoside Triphosphate Diphosphohydrolase (NTPDase) Inhibitors With Selectivity for NTPDase2 and NTPDase3
  作者：Younis Baqi、Mahmoud Rashed、Laura Schäkel、Enas M. Malik、Julie Pelletier、Jean Sévigny、Amelie Fiene、Christa E. Müller

  DOI：10.3389/fphar.2020.01282

  日期：——

  Ectonucleoside triphosphate diphosphohydrolases (NTPDases) catalyze the hydrolysis of nucleoside tri- and di-phosphates to mono-phosphates. The products are subsequently hydrolyzed by ecto-5 '-nucleotidase (ecto-5 '-NT) to nucleosides. NTPDase inhibitors have potential as novel drugs, e.g., for the treatment of inflammation, neurodegenerative diseases, and cancer. In this context, a series of anthraquinone derivatives structurally related to the anthraquinone dye reactive blue-2 (RB-2) was synthesized and evaluated as inhibitors of human NTPDases utilizing a malachite green assay. We identified several potent and selective inhibitors of human NTPDase2 and -3. Among the most potent NTPDase2 inhibitors were 1-amino-4-(9-phenanthrylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (20, PSB-16131, IC(50)of 539 nM) and 1-amino-4-(3-chloro-4-phenylsulfanyl)phenylamino-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (48, PSB-2020, IC(50)of 551 nM). The most potent NTPDase3 inhibitors were 1-amino-4-[3-(4,6-dichlorotriazin-2-ylamino)-4-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (42, PSB-1011, IC(50)of 390 nM) and 1-amino-4-(3-carboxy-4-hydroxyphenylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (33, PSB-2046, IC(50)of 723 nM). The best NTPDase2 inhibitor 20 showed a non-competitive inhibition type, while the NTPDase3 inhibitor 42 behaved as a mixed-type inhibitor. These potent compounds were found to be selective vs. other NTPDases. They will be useful tools for studying the roles of NTPDase2 and -3 in physiology and under pathological conditions.
• Development of Potent and Selective Inhibitors of <i>ecto</i>-5′-Nucleotidase Based on an Anthraquinone Scaffold
  作者：Younis Baqi、Sang-Yong Lee、Jamshed Iqbal、Peter Ripphausen、Anne Lehr、Anja B. Scheiff、Herbert Zimmermann、Jürgen Bajorath、Christa E. Müller

  DOI：10.1021/jm901851t

  日期：2010.3.11

  ecto-5'-Nucleotidase (eN, CD73) plays it major role in controlling extracellular adenosine levels. eN inhibitors have potential its novel drugs, for example, for the treatment of cancer. In the present study, we synthesized and investigated a series of 55 anthraquinone derivatives as potential inhibitors of eN, I I of which are novel compounds and another I I of which had previously been described but have now been synthesized by all improved method. We identified several potent inhibitors of rat eN. The most potent compounds were 1-amino-4-[4-fluoro-2-carboxyphenylamino]-9, 10-dioxo-9, 10-dihydroanthracene-2-sulfonate (45, PSB-0952, K-i = 260 nM) and 1-amino-4-[2-anthracenylamino]-9, 10-dioxo-9, 10-dihydroanthracene-2-sulfonate (52, PSB-0963, 150 nM), with 52 being the most potent eN inhibitor described to date. Selected compounds were further characterized and found to exhibit a competitive mechanism of inhibition. Investigations of ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) and the P2Y receptor subtypes P2Y(2), P2Y(4), P2Y(6), and P2Y(12) showed that compound 45 exhibited the highest degree of selectivity (> 150-fold).
• 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.