[6-chloro-1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid | 823178-05-8

• 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: [6-chloro-1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid
• 英文别名: 2-{6-chloro-1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}acetic acid；2-[6-chloro-1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid
• CAS: 823178-05-8
• 化学式: C₁₉H₁₅Cl₂NO₄
• 分子量: 392.238
• InChiKey: KSSRZUXSJXSLKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [6-chloro-1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid 、 3-nitroxypropylammonium nitrate 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以59%的产率得到2-{6-chloro-1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}-N-[3-(nitrooxy)propyl]acetamide
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Indomethacin Derivatives as Cyclooxygenase-2 Inhibiting Nitric Oxide Donors

  摘要：

  Indomethacin, a nonselective cyclooxygenase (COX) inhibitor, was modified in three distinct regions in an attempt both to increase cyclooxygenase-2 (COX-2) selectivity and to enhance drug safety by covalent attachment of an organic nitrate moiety as a nitric oxide donor. A human whole-blood COX assay shows the modifications on the 3-acetic acid part of the indomethacin yielding an amide-nitrate derivative 32 and a sulfonamide-nitrate derivative 61 conferred COX-2 selectivity. Along with their respective des-nitrate analogs, for example, 31 and 62, the nitrates 32 and 61 were effective antiinflammatory agents in the rat air-pouch model. After oral dosing, though, only 32 increased nitrate and nitrite levels in rat plasma, indicating that its nitrate tether served as a nitric oxide donor in vivo. In a rat gastric injury model, examples 31 and 32 both show a 98% reduction in gastric lesion score compared to that of indomethacin. In addition, the nitrated derivative 32 inducing 85% fewer gastric lesions when coadministered with aspirin as compared to the combination of aspirin and valdecoxib.

  DOI：

  10.1021/jm0611861
• 作为产物：
  描述：

  2-(1-苯甲酰基-5-羟基-2-甲基吲哚-3-基)乙酸 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 生成 [6-chloro-1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid
  参考文献：
  名称：

  Synthesis of COX-2 and FAAH inhibitors

  摘要：

  描述了制备对COX-2抑制剂有用的吲哚和在这些方法中有用的中间体的方法。

  公开号：

  US20050234244A1

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。
• Modulators of CRTH2 activity
  申请人：Chien Yueh-Tyng

  公开号：US20060135591A1

  公开（公告）日：2006-06-22

  Modulators of the CRTH2 receptor and their use in the treatment of various disorders, including asthma are described.

  介绍了 CRTH2 受体的调节剂及其在治疗包括哮喘在内的各种疾病中的应用。
• WO2006/99416
  申请人：——

  公开号：——

  公开（公告）日：——
• COX-2 and FAAH inhibitors
  申请人：Bartolini Wilmin

  公开号：US20050032747A1

  公开（公告）日：2005-02-10

  The invention features compounds that inhibit COX-2 and/or FAAH. The COX-2 inhibitors are selective COX-2 inhibitors in that they are selective for COX-2 compared to COX-1. Certain of the FAAH inhibitors are selective for FAAH relative to COX-2. Certain of the COX-2 inhibitors, in addition for being selective for COX-2 relative to COX-1, are selective for COX-2 relative to FAAH.
• Modulators of CRTH2 Activity
  申请人：Chien Yueh-Tyng

  公开号：US20070161698A1

  公开（公告）日：2007-07-12

  Modulators of the CRTH2 receptor and their use in the treatment of various disorders, including asthma are described.