4-methyl‐N‐(4‐(methylsulfonyl)benzylidene)aniline | 1239645-74-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-methyl‐N‐(4‐(methylsulfonyl)benzylidene)aniline
• 英文别名: N-(4-methylphenyl)-1-(4-methylsulfonylphenyl)methanimine
• CAS: 1239645-74-9
• 化学式: C₁₅H₁₅NO₂S
• 分子量: 273.356
• InChiKey: NIWBMZLGZTYIBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  54.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-methyl‐N‐(4‐(methylsulfonyl)benzylidene)aniline 、 甲氧基乙酸 在 三乙胺 、 对甲苯磺酰氯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以69%的产率得到(3S,4R)-3‐methoxy‐4‐(4‐(methylsulfonyl)phenyl)‐1‐(p‐tolyl)azetidin‐2‐one
  参考文献：
  名称：

  新型 1,4-二芳基氮杂环丁烷-2-one 衍生物（β-内酰胺类）作为选择性环加氧酶-2 抑制剂的设计、合成和生物学评价

  摘要：

  设计并合成了一系列新的 1,4-二芳基氮杂环丁烷-2-one 衍生物（β-内酰胺类），以评估其作为选择性环氧合酶-2（COX-2）抑制剂的生物活性。体外 COX-1 和 COX-2 抑制研究表明，所有化合物都是 COX-2 同工酶的选择性抑制剂，IC50 值在 0.05-0.11 µM 范围内，COX-2 选择性指数在 170-703.7 范围内。在合成的β-内酰胺类中，3-甲氧基-4-(4-(甲基磺酰基)苯基)-1-(3,4,5-三甲氧基苯基)氮杂环丁烷-2-酮(4j)在N-1苯基上具有三甲氧基环表现出最高的 COX-2 抑制选择性和效力，甚至比参考药物塞来昔布更有效。还使用福尔马林试验测定合成化合物的镇痛活性。化合物4f在合成的分子中表现出最好的镇痛活性。分子模型研究表明，甲基磺酰基药效团可以插入到 COX-2 活性位点的二级口袋中，与 Arg513 相互作用。获得的结构-活性数据表明

  DOI：

  10.1002/ardp.201900293
• 作为产物：
  描述：

  乙烷,三氯氟- 在 potassium peroxymonosulfate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 10.0h， 生成 4-methyl‐N‐(4‐(methylsulfonyl)benzylidene)aniline
  参考文献：
  名称：

  Analogue-based design, synthesis and docking of non-steroidal anti-inflammatory agents. Part 2: Methyl sulfanyl/methyl sulfonyl substituted 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-ones

  摘要：

  A series of methyl sulfanyl/methyl sufonyl substituted 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-one were designed using analogue-based design, scaffold hopping and shape similarity matching. The designed compounds were synthesized in 2-3 steps with simple chemistry and screened by ovine cyclooxygenases (COXs) inhibitory assay and carrageenan-induced rat paw edema assay. Among the screened compounds, two compounds exhibited 100% cyclooxygenase-2 (COX-2) inhibitory potency without showing cycloxygenase-1 (COX-1) inhibition at 20 mu M. The compounds also showed promising in vivo anti-inflammatory potential. A structure-activity relationship within the dataset was established by correlating the effect of aromatic ring substituent constants, structural variables and physico-chemical descriptors with in vivo anti-inflammatory activity. Molecular docking studies were also performed on the title compounds to study the binding interactions to COX-2 active site residues. The experimentally determined COX-2 inhibitory activity was found moderately correlating with binding modes predicted for compounds by Glide XP dock scoring function. The 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-one pharmacophore reported herein should be a new lead for further development of novel non-steroidal anti-inflammatory agents. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.069

文献信息

• Synthesis and biologic evaluation of new 3-phenoxyazetidin-2-one derivatives as selective cyclooxygenase-2 inhibitors
  作者：H. Arefi、A. Zarghi

  DOI：10.1007/s00044-012-0387-1

  日期：2013.8

  A new series of 3-phenoxyazetidin-2-ones (beta-lactams) were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 inhibition studies showed that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the 0.054-0.095 mu M range, and COX-2 selectivity indexes in the 228.47-355.6 range. Among the synthesized compounds, 1-(4-methoxyphenyl)-4-(4-(methylsulfonyl)phenyl)-3-phenoxyazetidin-2-one (4j) possessing methoxy group at the para position of N-1 phenyl ring exhibited the highest COX-2 inhibitory selectivity and potency even more potent than the reference drug celecoxib. Molecular modeling studies indicated that the methylsulfonyl pharmacophore group can be inserted into the secondary pocket of COX-2 active site.
• Analogue-based design, synthesis and docking of non-steroidal anti-inflammatory agents. Part 2: Methyl sulfanyl/methyl sulfonyl substituted 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-ones
  作者：E. Manivannan、S.C. Chaturvedi

  DOI：10.1016/j.bmc.2012.09.069

  日期：2012.12

  A series of methyl sulfanyl/methyl sufonyl substituted 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-one were designed using analogue-based design, scaffold hopping and shape similarity matching. The designed compounds were synthesized in 2-3 steps with simple chemistry and screened by ovine cyclooxygenases (COXs) inhibitory assay and carrageenan-induced rat paw edema assay. Among the screened compounds, two compounds exhibited 100% cyclooxygenase-2 (COX-2) inhibitory potency without showing cycloxygenase-1 (COX-1) inhibition at 20 mu M. The compounds also showed promising in vivo anti-inflammatory potential. A structure-activity relationship within the dataset was established by correlating the effect of aromatic ring substituent constants, structural variables and physico-chemical descriptors with in vivo anti-inflammatory activity. Molecular docking studies were also performed on the title compounds to study the binding interactions to COX-2 active site residues. The experimentally determined COX-2 inhibitory activity was found moderately correlating with binding modes predicted for compounds by Glide XP dock scoring function. The 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-one pharmacophore reported herein should be a new lead for further development of novel non-steroidal anti-inflammatory agents. (C) 2012 Elsevier Ltd. All rights reserved.
• Design, synthesis, and biological evaluation of new 1,4‐diarylazetidin‐2‐one derivatives (β‐lactams) as selective cyclooxygenase‐2 inhibitors
  作者：Hadi Arefi、Nima Naderi、Amir B. Irani Shemirani、Mina Kiani Falavarjani、Mahsa Azami Movahed、Afshin Zarghi

  DOI：10.1002/ardp.201900293

  日期：2020.3

  A new series of 1,4‐diarylazetidin‐2‐one derivatives (β‐lactams) were designed and synthesized to evaluate their biological activities as selective cyclooxygenase‐2 (COX‐2) inhibitors. In vitro COX‐1 and COX‐2 inhibition studies showed that all compounds were selective inhibitors of the COX‐2 isozyme with IC50 values in the 0.05–0.11 µM range, and COX‐2 selectivity indexes in the range of 170–703.7

  设计并合成了一系列新的 1,4-二芳基氮杂环丁烷-2-one 衍生物（β-内酰胺类），以评估其作为选择性环氧合酶-2（COX-2）抑制剂的生物活性。体外 COX-1 和 COX-2 抑制研究表明，所有化合物都是 COX-2 同工酶的选择性抑制剂，IC50 值在 0.05-0.11 µM 范围内，COX-2 选择性指数在 170-703.7 范围内。在合成的β-内酰胺类中，3-甲氧基-4-(4-(甲基磺酰基)苯基)-1-(3,4,5-三甲氧基苯基)氮杂环丁烷-2-酮(4j)在N-1苯基上具有三甲氧基环表现出最高的 COX-2 抑制选择性和效力，甚至比参考药物塞来昔布更有效。还使用福尔马林试验测定合成化合物的镇痛活性。化合物4f在合成的分子中表现出最好的镇痛活性。分子模型研究表明，甲基磺酰基药效团可以插入到 COX-2 活性位点的二级口袋中，与 Arg513 相互作用。获得的结构-活性数据表明