4‐chloro‐N‐(4‐(methylsulfonyl)benzylidene)aniline | 1239645-73-8

• 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‐chloro‐N‐(4‐(methylsulfonyl)benzylidene)aniline
• 英文别名: (E)-4-Chloro-N-[4-(methylsulfonyl)benzylidene]aniline；N-(4-chlorophenyl)-1-(4-methylsulfonylphenyl)methanimine
• CAS: 1239645-73-8
• 化学式: C₁₄H₁₂ClNO₂S
• 分子量: 293.774
• InChiKey: AMDZODROWGLIOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 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‐chloro‐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65%的产率得到(3S,4R)-1‐(4‐chlorophenyl)‐3‐methoxy‐4‐(4‐(methylsulfonyl)phenyl)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：

  4-chloro-N-[4-methylsulfanylbenzylidene]aniline 在 potassium peroxymonosulfate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 4‐chloro‐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.