[5-methoxy-2-methyl-1-(1-methyl-piperidin-4-yl)-1H-indol-3-yl]-acetic acid ethyl ester | 924265-22-5

• 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: [5-methoxy-2-methyl-1-(1-methyl-piperidin-4-yl)-1H-indol-3-yl]-acetic acid ethyl ester
• 英文别名: Ethyl 2-[5-methoxy-2-methyl-1-(1-methylpiperidin-4-yl)indol-3-yl]acetate
• CAS: 924265-22-5
• 化学式: C₂₀H₂₈N₂O₃
• 分子量: 344.454
• InChiKey: FIYYTWMTPAOOPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  43.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [5-methoxy-2-methyl-1-(1-methyl-piperidin-4-yl)-1H-indol-3-yl]-acetic acid ethyl ester 在 potassium hydroxide 、 溶剂黄146 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 0.5h， 以59.2%的产率得到[5-methoxy-2-methyl-1-(1-methyl-piperidin-4-yl)-1H-indol-3-yl]-acetic acid
  参考文献：
  名称：

  Synthesis and investigations of double-pharmacophore ligands for treatment of chronic and neuropathic pain

  摘要：

  Acids 9a-f as possible bivalent ligands designed as a structural combination of opioid mu-agonist (Fentanyl) and NSAID ( Indomethacin) activities and produced compounds which were tested as analgesics. The obtained series of compounds exhibits low affinity and activity both at opioid receptors and as cyclooxygenase ( COX) inhibitors. One explanation of the weak opioid activity could be stereochemical peculiarities of these bivalent compounds which differ significantly from the fentanyl skeleton. The absence of significant COX inhibitory properties could be explained by the required substitution of an acyl fragment in the indomethacin structure for 4-piperidyl. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.05.065
• 作为产物：
  描述：

  ethyl 4-(2-(4-methoxyphenyl)-2-(1-methylpiperidin-4-yl)hydrazineylidene)pentanoate 在 盐酸 作用下， 以 乙醇 为溶剂， 以75.6%的产率得到[5-methoxy-2-methyl-1-(1-methyl-piperidin-4-yl)-1H-indol-3-yl]-acetic acid ethyl ester
  参考文献：
  名称：

  Synthesis and investigations of double-pharmacophore ligands for treatment of chronic and neuropathic pain

  摘要：

  Acids 9a-f as possible bivalent ligands designed as a structural combination of opioid mu-agonist (Fentanyl) and NSAID ( Indomethacin) activities and produced compounds which were tested as analgesics. The obtained series of compounds exhibits low affinity and activity both at opioid receptors and as cyclooxygenase ( COX) inhibitors. One explanation of the weak opioid activity could be stereochemical peculiarities of these bivalent compounds which differ significantly from the fentanyl skeleton. The absence of significant COX inhibitory properties could be explained by the required substitution of an acyl fragment in the indomethacin structure for 4-piperidyl. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.05.065

文献信息

• SUBSTITUTED 2-(5-HYDROXY-2-METHYL-1H-INDOLE-3-YL)ACETIC ACIDS AND ETHERS THEREOF AND THE USE OF SAME TO TREAT VIRAL DISEASES
  申请人：Ivashchenko Andrey Alexandrovich

  公开号：US20110230524A1

  公开（公告）日：2011-09-22

  The present invention relates to novel substituted 2-(5-hydroxy-2-methyl-1H-indol-3-yl)acetic acids, to novel antiviral active ingredients, pharmaceutical compositions, antiviral medicaments, methods for prophylaxis and treatment of viral diseases particularly caused by influenza viruses and infectious hepatisis C (HCV) viruses. Novel substituted 2-(5-hydroxy-2-methyl-1H-indol-3-yl)acetic acids, their esters of the general formula 1 and pharmaceutically acceptable salts and/or hydrates thereof have been disclosed wherein: R 1 represents amino group substituent selected from hydrogen, optionally substituted C 1 -C 5 alkyl, acyl or sulfonyl; R 2 and R 4 independently of each other represent alkyl substituent selected from hydrogen, halogen, optionally substituted C 1 -C 3 alkyl, optionally substituted hydroxyl, optionally substituted amino group, optionally substituted aminomethyl, substituted mercapto group; R 3 represents hydrogen, optionally substituted lower C 1 -C 5 alkyl; R 5 represents cyclic system substituent selected from hydrogen, fluorine, trifluoromethyl, carboxy group, alkyloxycarbonyl, possibly substituted aryl, heterocyclyl, optionally substituted aminomethyl, cyano group; R 6 represents hydroxyl group substituent selected from hydrogen, optionally substituted C 1 -C 5 alkyl, acyl.

  本发明涉及新的取代2-(5-羟基-2-甲基-1H-吲哚-3-基)乙酸，新的抗病毒活性成分，制药组合物，抗病毒药物，以及用于预防和治疗由流感病毒和丙型肝炎病毒（HCV）引起的病毒性疾病的方法。已经披露了新的取代2-(5-羟基-2-甲基-1H-吲哚-3-基)乙酸，其酯具有一般式1和其药用可接受的盐和/或水合物其中：R1代表氨基取代基，可选地取代的C1-C5烷基，酰基或磺酰基；R2和R4独立地代表氢，卤素，可选地取代的C1-C3烷基，可选地取代的羟基，可选地取代的氨基基团，可选地取代的氨甲基，取代的巯基团；R3代表氢，可选地取代的较低C1-C5烷基；R5代表环系统取代基，选择自氢，氟，三氟甲基，羧基，烷氧羰基，可能取代的芳基，杂环烷基，可选地取代的氨甲基，氰基；R6代表羟基取代基，选择自氢，可选地取代的C1-C5烷基，酰基。
• Synthesis of 2-Methyl-3-indolylacetic Derivatives as Anti-Inflammatory Agents That Inhibit Preferentially Cyclooxygenase 1 without Gastric Damage
  作者：Elisa Perissutti、Ferdinando Fiorino、Christian Renner、Beatrice Severino、Fiorentina Roviezzo、Lidia Sautebin、Antonietta Rossi、Giuseppe Cirino、Vincenzo Santagada、Giuseppe Caliendo

  DOI：10.1021/jm0608199

  日期：2006.12.1

  Novel substituted 2-methyl-3-indolylacetic derivatives were synthesized and evaluated for their activity in vitro and in vivo on COX-1 and COX-2. Active compounds were screened to determine their gastrointestinal tolerability in vivo in the rat. Results showed that 3 and 4 preferentially inhibited COX-1 in vitro and in vivo. MD simulations indicated an induced fit for COX-1 but not for COX-2, probably because of a lower plasticity of the latter.
• US8481587B2
  申请人：——

  公开号：US8481587B2

  公开（公告）日：2013-07-09
• Synthesis and investigations of double-pharmacophore ligands for treatment of chronic and neuropathic pain
  作者：Ruben Vardanyan、Gokhale Vijay、Gary S. Nichol、Lu Liu、Isuru Kumarasinghe、Peg Davis、Todd Vanderah、Frank Porreca、Josephine Lai、Victor J. Hruby

  DOI：10.1016/j.bmc.2009.05.065

  日期：2009.7

  Acids 9a-f as possible bivalent ligands designed as a structural combination of opioid mu-agonist (Fentanyl) and NSAID ( Indomethacin) activities and produced compounds which were tested as analgesics. The obtained series of compounds exhibits low affinity and activity both at opioid receptors and as cyclooxygenase ( COX) inhibitors. One explanation of the weak opioid activity could be stereochemical peculiarities of these bivalent compounds which differ significantly from the fentanyl skeleton. The absence of significant COX inhibitory properties could be explained by the required substitution of an acyl fragment in the indomethacin structure for 4-piperidyl. Published by Elsevier Ltd.