8-(3-(3-aminobenzamide)-4-methylbenzamido)-naphthalene-1,3,5-trisulfonic acid trisodium salt | 17804-51-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-(3-(3-aminobenzamide)-4-methylbenzamido)-naphthalene-1,3,5-trisulfonic acid trisodium salt
• 英文别名: 8-(3-(3-aminobenzamido)-4-methylbenzamido)naphthalene-1,3,5-trisulfonic acid trisodium salt；Einecs 241-777-8；sodium;8-[[3-[(3-aminobenzoyl)amino]-4-methylbenzoyl]amino]naphthalene-1,3,5-trisulfonate
• CAS: 17804-51-2
• 化学式: C₂₅H₁₈N₃O₁₁S₃*3Na
• 分子量: 701.599
• InChiKey: IROYMJWWVOTZRG-UHFFFAOYSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -1.05
• 重原子数：
  43
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  281
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  光气 、 8-(3-(3-aminobenzamide)-4-methylbenzamido)-naphthalene-1,3,5-trisulfonic acid trisodium salt 以 水 、 甲苯 为溶剂， 生成 suramin sodium
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Suramin-Derived P2Y₁₁ Receptor Antagonists with Nanomolar Potency

  摘要：

  Selective and potent P2Y(11) receptor antagonists have yet to be developed, thus impeding an evaluation of this G protein-coupled receptor mainly expressed on immune cells. Taking suramin with moderate inhibitory potency as a template, 18 ureas with variations of the methyl groups of suramin and their precursors were functionally tested at P2Y(11), P2Y(1), and P2Y(2) receptors. Fluorine substitution of the methyl groups of suramin led to the first nanomolar P2Y(11) antagonist (8f, NF157, pK(i): 7.35). For selectivity, 8f was also tested at various P2X receptors. 8f displayed selectivity for P2Y(11) over P2Y(1) (> 650-fold), P2Y(2) (> 650-fold), P2X(2) (3-fold), P2X(3) (8-fold), P2X(4) (> 22-fold), and P2X(7) (> 67-fold) but no selectivity over P2X(1). QSAR studies confirm that residues with favored resonance and size parameters in the aromatic linker region can indeed lead to an increased potency as is the case for 8f. A symmetric structure linking two anionic clusters seems to be required for bioactivity. 8f may be helpful for studies evaluating the physiological role of P2Y(11) receptors.

  DOI：

  10.1021/jm050301p
• 作为产物：
  描述：

  suramin sodium 在 水 作用下， 反应 144.0h， 生成 8-(3-(3-aminobenzamide)-4-methylbenzamido)-naphthalene-1,3,5-trisulfonic acid trisodium salt
  参考文献：
  名称：

  苏拉明在水溶液中的稳定性；在患者中寻找苏拉明代谢物的可能意义

  摘要：

  已确定苏拉明水溶液的稳定性。HPLC 可检测到的唯一降解产物是胺前体 2。显示了不同温度下苏拉明的分解动力学。由于一级动力学，Arrhenius 方程可用于评估分解数据。在反应常数和温度之间获得了良好的相关性 (r = 0.9898)。在 37°C 下 42 天后，2% 的苏拉明被水解。讨论了我们的结果对寻找患者苏拉明代谢物的可能影响。

  DOI：

  10.1002/ardp.19963290502

文献信息

• [EN] METHODS OF MANUFACTURE OF SURAMIN<br/>[FR] PROCÉDÉS DE FABRICATION DE LA SURAMINE
  申请人：PERFECT DAYLIGHT LTD

  公开号：WO2022026627A1

  公开（公告）日：2022-02-03

  Pharmaceutical compositions comprising suramin and methods of preparing synthetic intermediates useful for the preparation of suramin are described herein.

  本文描述了包含苏拉明的药物组合物，以及用于制备苏拉明的合成中间体的方法。
• Nickel; Haack; Widjaja, Arzneimittel-Forschung/Drug Research, 1986, vol. 36, # 8, p. 1153 - 1157
  作者：Nickel、Haack、Widjaja、Ardanuy、Gurgel、Duewel、Loewe、Raether

  DOI：——

  日期：——
• Klinger, Markus; Freissmuth, Michael; Nickel, Peter, Molecular Pharmacology, <hi>1999</hi>, vol. 55, # 3, p. 462 - 472
  作者：Klinger, Markus、Freissmuth, Michael、Nickel, Peter、Staebler-Schwarzbart, Margit、Kassack, Matthias、Suko, Josef、Hohenegger, Martin

  DOI：——

  日期：——
• Synthesis and Structure−Activity Relationships of Suramin-Derived P2Y₁₁ Receptor Antagonists with Nanomolar Potency
  作者：Heiko Ullmann、Sabine Meis、Darunee Hongwiset、Claudia Marzian、Michael Wiese、Peter Nickel、Didier Communi、Jean-Marie Boeynaems、Christian Wolf、Ralf Hausmann、Günther Schmalzing、Matthias U. Kassack

  DOI：10.1021/jm050301p

  日期：2005.11.1

  Selective and potent P2Y(11) receptor antagonists have yet to be developed, thus impeding an evaluation of this G protein-coupled receptor mainly expressed on immune cells. Taking suramin with moderate inhibitory potency as a template, 18 ureas with variations of the methyl groups of suramin and their precursors were functionally tested at P2Y(11), P2Y(1), and P2Y(2) receptors. Fluorine substitution of the methyl groups of suramin led to the first nanomolar P2Y(11) antagonist (8f, NF157, pK(i): 7.35). For selectivity, 8f was also tested at various P2X receptors. 8f displayed selectivity for P2Y(11) over P2Y(1) (> 650-fold), P2Y(2) (> 650-fold), P2X(2) (3-fold), P2X(3) (8-fold), P2X(4) (> 22-fold), and P2X(7) (> 67-fold) but no selectivity over P2X(1). QSAR studies confirm that residues with favored resonance and size parameters in the aromatic linker region can indeed lead to an increased potency as is the case for 8f. A symmetric structure linking two anionic clusters seems to be required for bioactivity. 8f may be helpful for studies evaluating the physiological role of P2Y(11) receptors.
• Stability of Suramin in Aqueous Solution; Possible Implications for the Search for Suramin Metabolites in Patients
  作者：Matthias Kassack、Peter Nickel

  DOI：10.1002/ardp.19963290502

  日期：——

  The stability of an aqueous solution of suramin has been determined. The only degradation product detectable by HPLC was the amine precursor 2. The decomposition kinetics of suramin at different temperatures are shown. Because of first order kinetics the Arrhenius equation could be used to evaluate the decomposition data. A good correlation was obtained between the reaction constants and the temperature

  已确定苏拉明水溶液的稳定性。HPLC 可检测到的唯一降解产物是胺前体 2。显示了不同温度下苏拉明的分解动力学。由于一级动力学，Arrhenius 方程可用于评估分解数据。在反应常数和温度之间获得了良好的相关性 (r = 0.9898)。在 37°C 下 42 天后，2% 的苏拉明被水解。讨论了我们的结果对寻找患者苏拉明代谢物的可能影响。