p-Bromobenzyl-indomethacin | 176174-97-3

• 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: p-Bromobenzyl-indomethacin
• 英文别名: 1-(4-bromobenzyl)-5-methoxy-2-methylindole-3-acetic acid；[1-(4-bromobenzyl)-5-methoxy-2-methyl-1H-indol-3-yl] acetic acid；[1-(4-bromobenzyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid；2-[1-[(4-bromophenyl)methyl]-5-methoxy-2-methylindol-3-yl]acetic acid
• CAS: 176174-97-3
• 化学式: C₁₉H₁₈BrNO₃
• 分子量: 388.261
• InChiKey: VYGRRQURXQHVSD-UHFFFAOYSA-N

物化性质

• 沸点：
  585.2±50.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  p-Bromobenzyl-indomethacin 在 tetraphosphorus decasulfide 、 氨 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 24.0h， 生成 1-(4-bromobenzyl)-3-[4-(4-Chlorophenyl)thiazol-2-ylmethyl]-5-methoxy-2-methylindole
  参考文献：
  名称：

  Thiazole analogues of the NSAID indomethacin as selective COX-2 Inhibitors

  摘要：

  The carboxyl group of the NSAID indomethacin was replaced with a variety of substituted thiazoles to obtain a series of potent, selective inhibitors of COX-2. Additional substitutions were made at the 1-position and 5-position of the indole of indomethacin. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00212-8
• 作为产物：
  描述：

  (5-甲氧基-2-甲基-1H-吲哚-3-基)-乙酸乙酯 在 sodium hydroxide 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 p-Bromobenzyl-indomethacin
  参考文献：
  名称：

  Thiazole analogues of the NSAID indomethacin as selective COX-2 Inhibitors

  摘要：

  The carboxyl group of the NSAID indomethacin was replaced with a variety of substituted thiazoles to obtain a series of potent, selective inhibitors of COX-2. Additional substitutions were made at the 1-position and 5-position of the indole of indomethacin. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00212-8

文献信息

• Ester and Amide Derivatives of the Nonsteroidal Antiinflammatory Drug, Indomethacin, as Selective Cyclooxygenase-2 Inhibitors
  作者：Amit S. Kalgutkar、Alan B. Marnett、Brenda C. Crews、Rory P. Remmel、Lawrence J. Marnett

  DOI：10.1021/jm000004e

  日期：2000.7.1

  exchanging the 2-methyl group on the indole ring in the ester and amide series with a hydrogen also generated inactive compounds. Inhibition kinetics revealed that indomethacin amides behave as slow, tight-binding inhibitors of COX-2 and that selectivity is a function of the time-dependent step. Conversion of indomethacin into ester and amide derivatives provides a facile strategy for generating highly selective

  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
• Heterocyclic compounds as COX-2 inhibitors
  申请人：Abbott Laboratories

  公开号：US05811425A1

  公开（公告）日：1998-09-22

  The present invention relates to COX-2 inhibitors of the formula: ##STR1## wherein, A=halogen, C.sub.1 -C.sub.6 alkyl, SR.sup.1 or OR.sup.1 ; B=O, or H,H; X=Br or Cl; L=5-,6- or 7-membered heteroatom containing rings and is preferrably a 5-membered heteroaromatics such as thiazole, oxazole, imidazole, or oxadiazole; n=1-6, wherein the (C) is optionally branched; R=optionally substituted aryl wherein aryl is selected from phenyl, pyridyl, naphthyl, benzothienyl, or quinoxolyl, alkyl, carboxyl, esters, amino, amide, or urea; and R.sup.1 =alkyl. The compounds are useful as research tools and could be useful as potential therapeutic agents in the inhibition of the PGHS-2 isozyme and in the treatment of inflammation in mammals including humans or other conditions associated with the production of prostaglandins.

  本发明涉及COX-2抑制剂的化学式：##STR1## 其中，A=卤素，C.sub.1-C.sub.6烷基，SR.sup.1或OR.sup.1；B=O，或H，H；X=Br或Cl；L=含有5、6或7个成员的杂原子环，最好是5个成员的杂芳烃，如噻唑，噁唑，咪唑或噁二唑；n=1-6，其中（C）可选择分支；R=可选择取代的芳基，其中芳基选自苯基，吡啶基，萘基，苯并噻吩基或喹喔基，烷基，羧基，酯，氨基，酰胺或脲；和R.sup.1 =烷基。这些化合物可用作研究工具，并且可能作为潜在的治疗剂在PGHS-2同工酶的抑制和治疗哺乳动物包括人类或其他与前列腺素产生有关的炎症状况中有用。
• Synthesis of indomethacin analogues for evaluation as modulators of MRP activity
  作者：Anita R. Maguire、Stephen J. Plunkett、Sébastien Papot、Martin Clynes、Robert O'Connor、Samantha Touhey

  DOI：10.1016/s0968-0896(00)00292-3

  日期：2001.3

  Synthesis of a range of indomethacin analogues, required for investigation in combination toxicity assays, bearing both N-benzyl and N-benzoyl groups, is described. (C) 2001 Elsevier Science Ltd. All rights reserved.
• US5639780A
  申请人：——

  公开号：US5639780A

  公开（公告）日：1997-06-17
• US5811425A
  申请人：——

  公开号：US5811425A

  公开（公告）日：1998-09-22