sodium 1-amino-2-methyl-4-[4-phenylamino-3-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene | 1052088-02-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: sodium 1-amino-2-methyl-4-[4-phenylamino-3-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene
• 英文别名: 1-amino-2-methyl-4-[4-phenylamino-3-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene sodium salt；Sodium;5-[(4-amino-3-methyl-9,10-dioxoanthracen-1-yl)amino]-2-anilinobenzenesulfonate
• CAS: 1052088-02-4
• 化学式: C₂₇H₂₀N₃O₅S*Na
• 分子量: 521.529
• InChiKey: NFBUBQGVQFORLJ-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.75
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  150
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-氨基-4-溴-2-甲基蒽醌 、 4-氨基二苯胺-2-磺酸 在 铜 作用下， 反应 0.08h， 以30%的产率得到sodium 1-amino-2-methyl-4-[4-phenylamino-3-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene
  参考文献：
  名称：

  High-Affinity, Non-Nucleotide-Derived Competitive Antagonists of Platelet P2Y₁₂ Receptors

  摘要：

  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.

  DOI：

  10.1021/jm9003297

文献信息

• Novel P2Y12 receptor antagonists
  申请人：Rheinische Friedrich-Wilhelms-Universität Bonn

  公开号：EP1967513A1

  公开（公告）日：2008-09-10

  The present invention relates to compounds of Formula I, in which A and B are independently CH2, O, S, NH, C=O, C=NH, C=S or C=N-OH; X is NH, O, S, C=O or CH2 and R1-R5 are as defined in claim 1, which are P2Y12 receptor antagonists and useful for treating, alleviating and/or preventing diseases and disorders related to P2Y12 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.

  本发明涉及化合物的I式，其中A和B分别为CH2、O、S、NH、C=O、C=NH、C=S或C=N-OH；X为NH、O、S、C=O或CH2，R1-R5如权利要求书中所定义，这些化合物是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紊乱，以及包含这些化合物的药物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，用于缓解、预防和/或治疗疾病和紊乱，特别是作为抗血栓药物用于抑制血小板聚集。
• 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。
• [EN] NOVEL P2Y12 RECEPTOR ANTAGONISTS<br/>[FR] NOUVEAUX ANTAGONISTES DU RÉCEPTEUR P2Y12
  申请人：UNIV BONN

  公开号：WO2008107211A2

  公开（公告）日：2008-09-12

  [EN] The present invention relates to novel P2Y₁₂ receptor antagonists useful for treating, alleviating and/or preventing diseases and disorders related to P2Y₁₂ 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.
  [FR] La présente invention concerne de nouveaux antagonistes du récepteur P2Y₁₂ utiles pour traiter, soulager et/ou prévenir des maladies et des états pathologiques liés à la fonction du récepteur P2Y₁₂ ainsi que des compositions pharmaceutiques comprenant ces composés et des procédés de préparation de ces composés. La présente invention concerne en outre l'utilisation de ces composés, seuls ou en combinaison avec d'autres agents thérapeutiques, pour soulager, prévenir et/ou traiter des maladies et états pathologiques, en particulier l'utilisation d'agents anti-thrombotiques pour inhiber l'agrégation plaquettaire.
• 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.