ethyl 2-(3-chlorophenylamino)-5-hydroxy-1H-benzo[g]indole-3-carboxylate | 1159577-17-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 2-(3-chlorophenylamino)-5-hydroxy-1H-benzo[g]indole-3-carboxylate
• 英文别名: 5-hydroxy-1H-benzo[g]indole-3-carboxylate, 14；ethyl 2-(3-chloroanilino)-5-hydroxy-1H-benzo[g]indole-3-carboxylate
• CAS: 1159577-17-9
• 化学式: C₂₁H₁₇ClN₂O₃
• 分子量: 380.831
• InChiKey: VFNRZHHIOIJKGR-UHFFFAOYSA-N

物化性质

• 熔点：
  204 °C(Solvent: Ethyl acetate; Cyclohexane)
• 沸点：
  626.6±55.0 °C(predicted)
• 密度：
  1.427±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  74.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl (2E/Z)-3-amino-3-[(3-chlorophenyl)amino]acrylate 、 1,4-萘醌 在 zinc(II) iodide 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 以35%的产率得到ethyl 2-(3-chlorophenylamino)-5-hydroxy-1H-benzo[g]indole-3-carboxylate
  参考文献：
  名称：

  Structural Optimization and Biological Evaluation of 2-Substituted 5-Hydroxyindole-3-carboxylates as Potent Inhibitors of Human 5-Lipoxygenase

  摘要：

  Pharmacological suppression of leukotriene biosynthesis by inhibitors of 5-lipoxygenase (5-LO) is a strategy to intervene with inflammatory and allergic disorders. We recently presented 2-amino-5-hydroxy-1H-indoles as efficient 5-LO inhibitors in cell-based and cell-free assays. Structural optimization led to novel benzo[g]indole-3-carboxylates exemplified by ethyl 2-(3-chlorobenzyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate (compound 11a), which inhibits 5-LO activity in human neutrophils and recombinant human 5-LO with IC50 values of 0.23 and 0.086 mu M, respectively. Notably, 11a efficiently blocks 5-LO product formation in human whole blood assays (IC50 = 0.83-1.6 mu M) and significantly prevented leukotriene B-4 production in pleural exudates of carrageenan-treated rats, associated with reduced severity of pleurisy. Together, on the basis of their high potency against 5-LO and the marked efficacy in biological systems, these novel and straightforward benzo[g]indole-3-carboxylates may have potential as anti-inflammatory therapeutics.

  DOI：

  10.1021/jm900212y

文献信息

• [DE] VERWENDUNG VON INDOL-3-CARBONSÄUREESTERN ZUR HEMMUNG DER MIKROSOMALEN PROSTAGLANDIN E2 SYNTHASE<br/>[EN] USE OF INDOLE-3-CARBOXYLIC ESTERS FOR INHIBITING MICROSOMAL PROSTAGLANDIN E2 SYNTHASE<br/>[FR] UTILISATION D'ESTERS DE L'ACIDE INDOL-3-CARBOXYLIQUE POUR L'INHIBITION DE LA PROSTAGLANDINE E2 SYNTHASE MICROSOMALE
  申请人：UNIV TUEBINGEN

  公开号：WO2009146696A1

  公开（公告）日：2009-12-10

  Die vorliegende Erfindung betrifft die Verwendung von lndol-3-carbonsäureestern und seiner Derivate zur Hemmung der induzierbaren mikrosomalen Prostaglandin E2 Synthase-1 und/oder zur Hemmung der 5-Lipoxygenase. Insbesondere betrifft die Erfindung die Verwendung von Derivaten des 3-Carboxy-aryl[g]indols, vor allem von 2-Aryl- und 2-Arylalkyl-Aryl[g]indol-3-carbonsäureestern sowie deren strukturellen Abkömmlingen zur Hemmung der induzierbaren mikrosomalen Prostaglandin E2 Synthase-1 und / oder zur Hemmung der 5-Lipoxygenase. Ferner betrifft die Erfindung die Verwendung von lndol-3-carbonsäureestern zur Herstellung eines Arzneimittels zur Behandlung von PGE2- und / oder 5-LO-vermittelter Erkrankungen und krankhafter Zustände, insbesondere von entzündlichen chronischen Entzündungen wie rheumatoide Arthritis, Osteoarthritis, Erkrankungen des kardiovaskulären Systems, Asthma, allergische Rhinitis, Multiple Sklerose, entzündliche Hauterkrankungen, Osteoporose und Krebs, Schmerz und Fieber, bei denen PGE2 und / oder 5-LO Produkte eine Rolle spielen.

  本发明涉及使用indol-3-羧酸酯及其衍生物来抑制可诱导的微粒体前列腺素E2合成酶-1和/或抑制5-脂氧合酶。具体涉及使用3-羧基芳基[g]吲哚的衍生物，特别是2-芳基和2-芳基烷基芳基[g]吲哚-3-羧酸酯及其结构衍生物来抑制可诱导的微粒体前列腺素E2合成酶-1和/或抑制5-脂氧合酶。此外，本发明涉及使用indol-3-羧酸酯来制备药物，用于治疗PGE2和/或5-LO介导的疾病和病态，特别是慢性炎症性疾病，如类风湿性关节炎，骨关节炎，心血管系统疾病，哮喘，过敏性鼻炎，多发性硬化症，炎性皮肤病，骨质疏松症和癌症，以及疼痛和发热，在其中PGE2和/或5-LO产物发挥作用。
• Structural Optimization and Biological Evaluation of 2-Substituted 5-Hydroxyindole-3-carboxylates as Potent Inhibitors of Human 5-Lipoxygenase
  作者：Eva-Maria Karg、Susann Luderer、Carlo Pergola、Ulrike Bühring、Antonietta Rossi、Hinnak Northoff、Lidia Sautebin、Reinhard Troschütz、Oliver Werz

  DOI：10.1021/jm900212y

  日期：2009.6.11

  Pharmacological suppression of leukotriene biosynthesis by inhibitors of 5-lipoxygenase (5-LO) is a strategy to intervene with inflammatory and allergic disorders. We recently presented 2-amino-5-hydroxy-1H-indoles as efficient 5-LO inhibitors in cell-based and cell-free assays. Structural optimization led to novel benzo[g]indole-3-carboxylates exemplified by ethyl 2-(3-chlorobenzyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate (compound 11a), which inhibits 5-LO activity in human neutrophils and recombinant human 5-LO with IC50 values of 0.23 and 0.086 mu M, respectively. Notably, 11a efficiently blocks 5-LO product formation in human whole blood assays (IC50 = 0.83-1.6 mu M) and significantly prevented leukotriene B-4 production in pleural exudates of carrageenan-treated rats, associated with reduced severity of pleurisy. Together, on the basis of their high potency against 5-LO and the marked efficacy in biological systems, these novel and straightforward benzo[g]indole-3-carboxylates may have potential as anti-inflammatory therapeutics.