1-(4-Chlorbenzoyl)-5-methoxy-2-methylindol-3-essigsaeureisopropylester

• 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: 1-(4-Chlorbenzoyl)-5-methoxy-2-methylindol-3-essigsaeureisopropylester
• 英文别名: Indomethacin Isopropyl Ester；propan-2-yl 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetate
• 化学式: C₂₂H₂₂ClNO₄
• 分子量: 399.874
• InChiKey: YCIPLRSQHFHPRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  57.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  吲哚美辛 、 异丙醇 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以84%的产率得到1-(4-Chlorbenzoyl)-5-methoxy-2-methylindol-3-essigsaeureisopropylester
  参考文献：
  名称：

  非甾体抗炎药消炎痛的酯和酰胺衍生物，作为选择性的环氧合酶2抑制剂。

  摘要：

  我们实验室的最新研究表明，底物类似物抑制剂（例如5,8,11,14-二十碳四丁酸）和非甾体抗炎药（NSAIDs）（例如吲哚美辛和甲氯芬那酸）中羧酸根部分的衍生会导致有效和选择性的环氧合酶-2（COX-2）抑制剂的产生（Kalgutkar等人，Proc.Natl.Acad.Sci.USA 2000，97，925-930）。本文总结了有关结构活性研究的细节，这些研究涉及将芳基丙烯酸NSAID消炎痛转化为COX-2选择性抑制剂。许多结构多样的吲哚美辛酯和酰胺都抑制纯化的人COX-2，其ICo5值在低纳摩尔范围内，但在高达66 microM的浓度下却不抑制绵羊的COX-1活性。吲哚美辛的伯和仲酰胺类似物作为COX-2抑制剂的作用要强于相应的叔酰胺。消炎痛酯或酰胺中的4-氯苯甲酰基被4-溴苄基官能团或氢取代，得到惰性化合物。同样，用氢交换酯和酰胺系列中的吲哚环上的2-甲基也产生了惰性化合物。抑制动力

  DOI：

  10.1021/jm000004e

文献信息

• NITROSATED NONSTEROIDAL ANTIINFLAMMATORY COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：EARL Richard A.

  公开号：US20100093708A1

  公开（公告）日：2010-04-15

  The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.

  该发明描述了新型的亚硝基化非甾体抗炎药（NSAIDs）及其药学上可接受的盐，以及包含至少一种亚硝基化NSAID的新型组合物，可选地包含至少一种捐赠、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮源性松弛因子水平或是一氧化氮合酶底物的化合物，以及/或至少一种治疗剂。该发明还提供包含至少一种亚硝基化NSAID和至少一种捐赠、转移或释放一氧化氮、提高内源性内皮源性松弛因子水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物和/或至少一种治疗剂的新型组合物。该发明还提供包含至少一种亚硝基化NSAID，可选地包括至少一种一氧化氮供体和/或至少一种治疗剂的新型套件。该发明还提供用于治疗炎症、疼痛和发热的方法；用于治疗胃肠道疾病的方法；用于促进伤口愈合的方法；用于治疗和/或预防由非甾体抗炎化合物使用引起的胃肠道、肾脏和/或呼吸道毒性的方法；用于治疗炎症性疾病状态和/或疾病的方法；以及用于治疗和/或预防眼科疾病和/或疾病的方法。
• BOLTZE K.-H.; BRENDLER O.; JACOBI H.; OPITZ W.; RADDATZ S.; SEIDEL P.-R.;+, ARZNEIMITTEL-FORSCH., 1980, 30, NO 8A, 2314-2325
  作者：BOLTZE K.-H.、 BRENDLER O.、 JACOBI H.、 OPITZ W.、 RADDATZ S.、 SEIDEL P.-R.、+

  DOI：——

  日期：——
• ORGANIC NITRIC OXIDE DONOR SALTS OF NONSTEROIDAL ANTIINFLAMMATORY COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Garvey David S.

  公开号：US20090048219A1

  公开（公告）日：2009-02-19

  The invention describes novel organic nitric oxide enhancing salts of nonsteroidal antiinflammatory drugs (NSAIDs) and novel compositions comprising at least one organic nitric oxide enhancing salt of an NSAID, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one organic nitric oxide enhancing salt of an NSAID, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating inflammation, pain and fever; (b) treating gastrointestinal disorders; (c) facilitating wound healing; (d) treating gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; (e) treating inflammatory disease states and/or disorders; (f) treating ophthalmic disorders; (h) treating peripheral vascular diseases; (i) treating diseases resulting from oxidative stress; (j) treating endothelial dysfunctions; and (k) treating diseases caused by endothelial dysfunctions. The organic nitric oxide enhancing compounds that form salts with the NSAIDs are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and/or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.
• US7163958B2
  申请人：——

  公开号：US7163958B2

  公开（公告）日：2007-01-16
• US7883714B2
  申请人：——

  公开号：US7883714B2

  公开（公告）日：2011-02-08