2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid benzyl ester | 26001-79-6

• 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: 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid benzyl ester
• 英文别名: [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid benzyl ester；1-(4-Chlorbenzoyl)-5-methoxy-2-methylindol-3-essigsaeurebenzylester；benzyl indomethacin；indomethacin benzyl ester；[1-(4-chloro-benzoyl)-5-methoxy-2-methyl-indol-3-yl]-acetic acid benzyl ester；Benzyl 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetate
• CAS: 26001-79-6
• 化学式: C₂₆H₂₂ClNO₄
• 分子量: 447.918
• InChiKey: NFFDSMIECKYFBD-UHFFFAOYSA-N

物化性质

• 沸点：
  552.4±50.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  57.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid benzyl ester 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 0.67h， 以84%的产率得到吲哚美辛
  参考文献：
  名称：

  取代吲哚的芳香族烯酰胺/烯复分解及其在吲哚美辛合成中的应用

  摘要：

  描述了烯酰胺/烯复分解的空间和电子效应，使用烯酰胺 - 烯复分解作为关键反应制备 2-取代吲哚和 3-取代吲哚的新方法，及其在吲哚美辛合成中的应用。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

  DOI：

  10.1002/ejoc.200900520
• 作为产物：
  描述：

  吲哚美辛 、 苯甲醇 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72%的产率得到2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid benzyl ester
  参考文献：
  名称：

  吲哚美辛作为选择性COX-2抑制剂的酯衍生物的合成及生物学评价

  摘要：

  吲哚美辛的酯衍生物是通过将吲哚美辛与等摩尔量的适当醇化合物在无水二氯甲烷中在DCC和DMAP存在下缩合而制备的。为了确认其结构，进行了由IR，1 H NMR，质量和微量分析组成的光谱研究。使用角叉菜胶大鼠爪浮肿方法进行体内抗炎研究，并通过溃疡指数法对合成化合物进行体内致溃疡研究。与消炎痛相比，在11种化合物中，化合物IIc显示出中等的抗炎活性，没有可观察到的致溃疡作用。此外，化合物IIc通过比色COX抑制剂筛选试验，以20μM的浓度对吲哚美辛和塞来昔布针对COX-1和COX-2酶进行了测试。发现化合物IIc对COX-2和COX-1酶具有活性，分别表现出62.0和12.9％的抑制作用。

  DOI：

  10.1007/s00044-011-9747-5

文献信息

• Design, synthesis and biological evaluation of hybrid nitroxide-based non-steroidal anti-inflammatory drugs
  作者：Komba Thomas、Terry W. Moody、Robert T. Jensen、Jason Tong、Cassie L. Rayner、Nigel L. Barnett、Kathryn E. Fairfull-Smith、Lisa A. Ridnour、David A. Wink、Steven E. Bottle

  DOI：10.1016/j.ejmech.2018.01.077

  日期：2018.3

  Dual-acting hybrid anti-oxidant/anti-inflammatory agents were developed employing the principle of pharmacophore hybridization. Hybrid agents were synthesized by combining stable anti-oxidant nitroxides with conventional non-steroidal anti-inflammatory drugs (NSAIDs). Several of the hybrid nitroxide-NSAID conjugates displayed promising anti-oxidant and anti-inflammatory effects on two Non-Small Cell

  利用药效团杂交原理开发了双效混合抗氧化剂/抗炎剂。通过将稳定的抗氧化剂硝基氧与传统的非甾体抗炎药（NSAID）相结合来合成混合药物。几种混合硝基氧-NSAID 缀合物对两种非小细胞肺癌 (NSCLC) 细胞（A549 和 NCI-H1299）以及改善 661 W 视网膜细胞诱导的氧化应激表现出良好的抗氧化和抗炎作用。一种酯连接的硝基氧-阿司匹林类似物 ( 27 ) 比母体化合物（阿司匹林）具有更好的抗炎作用（环氧合酶抑制），并且还表现出与抗氧化剂 Tempol 相似的活性氧清除活性。此外，与抗炎药物吲哚美辛 ( 39 ) 连接的硝基氧化物可显着改善氧化应激对 661 W 视网膜神经元的影响，其功效大于或等于抗氧化剂叶黄素。混合缀合物的其他例子显示出有希望的抗癌活性，正如它们对 A549 NSCLC 细胞增殖的抑制作用所证明的那样。
• Boltze; Brendler; Jacobi, Arzneimittel-Forschung/Drug Research, 1980, vol. 30, # 8 A, p. 1314 - 1325
  作者：Boltze、Brendler、Jacobi、Opitz、Raddatz、Seidel、Vollbrecht

  DOI：——

  日期：——
• ortho-Carbaborane derivatives of indomethacin as cyclooxygenase (COX)-2 selective inhibitors
  作者：Matthias Scholz、Anna L. Blobaum、Lawrence J. Marnett、Evamarie Hey-Hawkins

  DOI：10.1016/j.bmc.2012.05.063

  日期：2012.8

  A series of novel indomethacin analogues with carbaboranes as three-dimensional substitutes for the chlorophenyl ring have been prepared. Their cyclooxygenase (COX) inhibition and enzyme selectivity has been tested and compared to the corresponding adamantyl analogues. Surprisingly, only the ortho-carbaborane derivatives were active compounds. Preliminary biological studies gave an interesting insight into the validity of employing carbaboranes as pharmacophores. (C) 2012 Elsevier Ltd. All rights reserved.
• Design and Synthesis of Indomethacin Analogues That Inhibit P-Glycoprotein and/or Multidrug Resistant Protein without Cox Inhibitory Activity
  作者：Mitsuhiro Arisawa、Yayoi Kasaya、Tohru Obata、Takuma Sasaki、Tomonori Nakamura、Takuya Araki、Koujirou Yamamoto、Akito Sasaki、Akihito Yamano、Mika Ito、Hiroshi Abe、Yoshihiro Ito、Satoshi Shuto

  DOI：10.1021/jm301084z

  日期：2012.9.27

  We designed and synthesized conformationally restricted analogues and regioisomers of the nonsteroidal anti-inflammatory drug indomethacin. Evaluation of the inhibitory effects of these compounds on COX, P-glycoprotein, and multidrug resistance indicated that NSAIDS modulation of multidrug-resistant P-glycoprotein and multidrug-resistant protein-1 is not associated with COX-1 and COX-2 inhibitory activities.
• Indomethacin Analogues that Enhance Doxorubicin Cytotoxicity in Multidrug Resistant Cells without Cox Inhibitory Activity
  作者：Mitsuhiro Arisawa、Yayoi Kasaya、Tohru Obata、Takuma Sasaki、Mika Ito、Hiroshi Abe、Yoshihiro Ito、Akihito Yamano、Satoshi Shuto

  DOI：10.1021/ml100292y

  日期：2011.5.12

  Conformationally restricted indomethacin analogues were designed and prepared from the corresponding 2-substituted indoles, which were synthesized by a one-pot isomerization/enamide-ene metathesis as the key reaction. Conformational analysis by calculations, NMR studies, and X-ray crystallography suggested that these analogues were conformationally restricted in the s-cis or the s-trans form due to the 2-substituent as expected. Their biological activities on cyclooxygenase-1 (COX-1) inhibition, cyclooxygenase-2 (COX-2) inhibition, and modulation of MRP-1-mediated multidrug resistance (MDR) are described. Some of these indomethacin analogues enhanced doxorubicin cytotoxicity, although they do not have any COX inhibitory activity, which suggests that the MDR-modulating effect of an NSAID can be unassociated with its COX-inhibitory activity. This may be an entry into the combination chemotherapy of doxorubicin with a MDR modulator.