1-(1H-benzo[d][1,2,3]triazol-1-yl)-2-(4-isobutylphenyl)propan-1-one | 230644-97-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 1-(1H-benzo[d][1,2,3]triazol-1-yl)-2-(4-isobutylphenyl)propan-1-one
• 英文别名: ibuprofen benzotriazolide；1-(benzotriazol-1-yl)-2-(4-isobutylphenyl)propan-1-one；1-(Benzotriazol-1-yl)-2-[4-(2-methylpropyl)phenyl]propan-1-one
• CAS: 230644-97-0
• 化学式: C₁₉H₂₁N₃O
• 分子量: 307.395
• InChiKey: YZTXRRMHGGKEOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  47.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(1H-benzo[d][1,2,3]triazol-1-yl)-2-(4-isobutylphenyl)propan-1-one 在 一水合肼 作用下， 以 1,4-二氧六环 为溶剂， 以89%的产率得到2-(4-异丁基苯基)丙酰肼
  参考文献：
  名称：

  Novel NSAID 1-acyl-4-cycloalkyl/arylsemicarbazides and 1-acyl-5-benzyloxy/hydroxy carbamoylcarbazides as potential anticancer agents and antioxidants

  摘要：

  The novel 1-acyl-4-cycloalkyl/arylsemicarbazides (5a-y) and 1-acyl-5-benzyloxy/hydroxy carbamoylcarbazides (8a-f) derived from the nonsteroidal anti-inflammatory drugs ibuprofen, fenoprofen and reduced ketoprofen were prepared, fully chemically characterized and evaluated for their cytostatic, antiviral and antioxidant activities. Compounds 5 and 8 consist of a region rich in electronegative atoms (five to nine nitrogen and oxygen atoms) framed by aryl or cycloalkyl residues on one or both terminal ends. The synthetic pathways applied for the preparation of the title compounds involved a benzotriazole as a synthetic auxiliary in several steps. Three of the tested compounds, namely 4-benzhydryl-1-[2-(3-phenoxyphenyl)propanoyl]semicarbazide (5l), 4-benzhydryl-1-[2-(3-benzylphenyl)propanoyl]semicarbazide (5s), and 4-benzhydryl-1-[2-(4-isobutylphenyl)propanoyl]semicarbazide (5f) showed pronounced antiproliferative activity in vitro against six cancer cell lines (IC50 = 3-23 mu M). The same compounds highly inhibited soybean lipoxygenase (IC50 = 60 and 51.5 mu M) and lipid peroxidation as well (99, 88 and 74%, respectively). 4-Benzyloxy-1-[2-(4-isobutylphenyl)propanoyl]semicarbazide (5t) and 5-benzyloxycarbamoyl-1-[2-(3-benzylphenyl)propanoyl]carbazide (8c) exerted complete lipid peroxidation inhibition. Semicarbazides 5w-y and carbazides 8d-f bearing a hydroxamic acid/hydroxyurea moiety showed a modest antiradical activity in DPPH test, while the best radical scavenger was 1-(1-benzotriazolecarbonyl)-4-benzyloxysemicarbazide (7). None of the compounds were inhibitory to a broad panel of DNA and RNA viruses in the cell culture at subtoxic concentrations. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.046
• 作为产物：
  描述：

  T406石油添加剂 在 三乙胺 作用下， 生成 1-(1H-benzo[d][1,2,3]triazol-1-yl)-2-(4-isobutylphenyl)propan-1-one
  参考文献：
  名称：

  Novel NSAID 1-acyl-4-cycloalkyl/arylsemicarbazides and 1-acyl-5-benzyloxy/hydroxy carbamoylcarbazides as potential anticancer agents and antioxidants

  摘要：

  The novel 1-acyl-4-cycloalkyl/arylsemicarbazides (5a-y) and 1-acyl-5-benzyloxy/hydroxy carbamoylcarbazides (8a-f) derived from the nonsteroidal anti-inflammatory drugs ibuprofen, fenoprofen and reduced ketoprofen were prepared, fully chemically characterized and evaluated for their cytostatic, antiviral and antioxidant activities. Compounds 5 and 8 consist of a region rich in electronegative atoms (five to nine nitrogen and oxygen atoms) framed by aryl or cycloalkyl residues on one or both terminal ends. The synthetic pathways applied for the preparation of the title compounds involved a benzotriazole as a synthetic auxiliary in several steps. Three of the tested compounds, namely 4-benzhydryl-1-[2-(3-phenoxyphenyl)propanoyl]semicarbazide (5l), 4-benzhydryl-1-[2-(3-benzylphenyl)propanoyl]semicarbazide (5s), and 4-benzhydryl-1-[2-(4-isobutylphenyl)propanoyl]semicarbazide (5f) showed pronounced antiproliferative activity in vitro against six cancer cell lines (IC50 = 3-23 mu M). The same compounds highly inhibited soybean lipoxygenase (IC50 = 60 and 51.5 mu M) and lipid peroxidation as well (99, 88 and 74%, respectively). 4-Benzyloxy-1-[2-(4-isobutylphenyl)propanoyl]semicarbazide (5t) and 5-benzyloxycarbamoyl-1-[2-(3-benzylphenyl)propanoyl]carbazide (8c) exerted complete lipid peroxidation inhibition. Semicarbazides 5w-y and carbazides 8d-f bearing a hydroxamic acid/hydroxyurea moiety showed a modest antiradical activity in DPPH test, while the best radical scavenger was 1-(1-benzotriazolecarbonyl)-4-benzyloxysemicarbazide (7). None of the compounds were inhibitory to a broad panel of DNA and RNA viruses in the cell culture at subtoxic concentrations. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.046

文献信息

• Microwave assisted synthesis and QSAR study of novel NSAID acetaminophen conjugates with amino acid linkers
  作者：Anand D. Tiwari、Siva S. Panda、Adel S. Girgis、Sandhyamayee Sahu、Riham F. George、Aladdin M. Srour、Brian La Starza、Abdullah M. Asiri、C. Dennis Hall、Alan R. Katritzky

  DOI：10.1039/c4ob01281j

  日期：——

  Novel, non-steroidal anti-inflammatory drug (NSAID), acetaminophen conjugates 6a–l with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates (6d, 6e, 6h, and 6k) exhibit more potent anti-inflammatory activity than their parent drugs, (b) the potent bis-conjugates show no visible stomach lesions

  新型非甾体抗炎药（NSAID），具有氨基酸连接基的对乙酰氨基酚共轭物6a-1，是利用苯并三唑化学方法合成的。获得的所有新型双结合物的生物学数据表明（a）一些双结合物（6d，6e，6h和6k）比其母体药物显示出更强的抗炎活性，（b）强大的双结合物没有显示出与高度致溃疡的母体药物相比，可见的胃部病变明显；（c）有效的生物活性化合物在应用抗炎剂量的5倍时没有死亡率或毒性症状。具有统计学意义的QSAR模型，描述了6a–l的抗炎特性（使用验证所观察到的生物活性的CODESSA-Pro获得N＝ 15，n＝ 3，R 2＝ 0.891，R 2 cvOO ＝ 0.770，R 2 cvMO ＝ 0.796，F＝ 29.904，s 2＝ 0.011）。
• Synthesis of Ibuprofen Hybrid Conjugates as Anti-Inflammatory and Analgesic Agents
  申请人：Augusta University Research Institute, Inc.

  公开号：US20210361597A1

  公开（公告）日：2021-11-25

  Disclosed herein as ibuprofen hybrid conjugates and methods of their use to reduce inflammation, pain, and fever. The ibuprofen conjugates have potent anti-inflammatory and analgesic properties with low potential for ulcerogenic activity. An exemplary compound is an ibuprofen-amino acid-4-aminophenol hybrid. Also disclosed are methods of treating or reducing inflammation, pain, and fever in a subject.

  本文披露了一种布洛芬杂交共轭物及其使用方法，用于减轻炎症、疼痛和发热。这些布洛芬共轭物具有强效的抗炎和镇痛特性，且溃疡生成活性低。其中一种示例化合物是布洛芬-氨基酸-4-氨基苯酚杂交物。此外，还披露了在受试者中治疗或减轻炎症、疼痛和发热的方法。
• The novel phosphoramidate derivatives of NSAID 3-hydroxypropylamides: Synthesis, cytostatic and antiviral activity evaluations
  作者：K. Wittine、K. Benci、Z. Rajić、B. Zorc、M. Kralj、M. Marjanović、K. Pavelić、E. De Clercq、G. Andrei、R. Snoeck

  DOI：10.1016/j.ejmech.2008.03.037

  日期：2009.1

  The target phosphoramidates 5a-e were prepared in one step from 3-hydroxypropyl derivatives 3a-e of nonsteroidal anti-inflammatory drugs (fenoprofen, ketoprofen, ibuprofen, indomethacin, diclofenac). The products 3a-e and 5a-e were evaluated for their cytostatic and antiviral activity against malignant tumour cell lines and normal human fibroblasts (WI 38). All phosphoramidate derivatives 5a-e possess significantly greater inhibitory activities than the corresponding 3-hydroxypropyl derivatives 3a-e, whereby compound 5a showed the most potent inhibitory activities against cervical, pancreatic and colon carcinoma cell lines (IC50 = 5 - 7 mu M), (C) 2008 Elsevier Masson SAS. All rights reserved.
• NSAID Conjugates with Carnosine and Amino Acids
  作者：Alan Katritzky、Sandhyamayee Sahu、Siva Panda、Abdullah Asiri

  DOI：10.1055/s-0033-1339920

  日期：——

  Benzotriazole-mediated syntheses of novel bioconjugates of nonsteroidal anti-inflammatory drugs with carnosine and with amino acids were prepared in yields of 50-97% as potential drug candidates.
• Chemistry around imidazopyrazine and ibuprofen: Discovery of novel fatty acid amide hydrolase (FAAH) inhibitors
  作者：Frédéric De Wael、Giulio G. Muccioli、Didier M. Lambert、Thérèse Sergent、Yves-Jacques Schneider、Jean-François Rees、Jacqueline Marchand-Brynaert

  DOI：10.1016/j.ejmech.2010.04.040

  日期：2010.9

  Based on the imidazo-[1,2-a]-pyrazin-3-(7H)-one scaffold, a dual action prodrug has been designed for combining antioxidant and anti-inflammatory activities, possibly unmasked upon oxidation. The construction of the target-molecule requires two building blocks, namely a 2-amino-1,4-pyrazine and a 2-ketoaldehyde. Attempts to synthesize the 2-ketoaldehyde (5a) derived from ibuprofen failed, but led to the corresponding 2-ketoaldoxime (7a) which could not be condensed with the pyrazine synthons. However, a model compound, i.e. phenylglyoxal aldoxime, reacted well under microwave activation to furnish novel imidazo[1,2-a]-pyrazine-3-(7H)-imine derivatives (18a,b). These heterobicycles behave as antioxidants by inhibiting the lipid peroxidation, and one compound (18b) is endowed with a significant anti-inflammatory effect in a cellular test. Unexpectedly, all the synthetic intermediates derived from ibuprofen are good inhibitors of FAAH, the most active compound (4a) featuring the 1,3-dithian-2-yl motif. (C) 2010 Elsevier Masson SAS. All rights reserved.