2-(4-(methylsulfonyl)phenyl)-3-phenylquinoline-4-carboxylic acid | 1219922-29-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(4-(methylsulfonyl)phenyl)-3-phenylquinoline-4-carboxylic acid
• 英文别名: 2-(4-methylsulfonylphenyl)-3-phenylquinoline-4-carboxylic acid
• CAS: 1219922-29-8
• 化学式: C₂₃H₁₇NO₄S
• 分子量: 403.458
• InChiKey: QIPZVWKUJCEWTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(4-(methylsulfonyl)phenyl)-2-phenylethanone 、 靛红 在 potassium hydroxide 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 48.25h， 以70%的产率得到2-(4-(methylsulfonyl)phenyl)-3-phenylquinoline-4-carboxylic acid
  参考文献：
  名称：

  Design, synthesis and biological evaluation of new 2,3-diarylquinoline derivatives as selective cyclooxygenase-2 inhibitors

  摘要：

  A new group of 2,3-diarylquinoline derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para-position of the C-2 phenyl ring were synthesized and evaluated as selective COX-2 inhibitors. In vitro COX-1/COX-2 structure-activity relationships were determined by varying the substituents on the C-4 quinoline ring. Among the 2,3-diarylquinolines, 2-(4-(methylsulfonyl) phenyl)-3-phenylquino-line-4-carboxylic acid (8) exhibited the highest potency and selectivity for COX-2 inhibitory activity (COX-2 IC50 = 0.07 mu M; selectivity index = 687.1) that was more selective than the reference drug celecoxib (COX-2 IC50 = 0.06 mu M; selectivity index = 405). A molecular modeling study where 8 was docked in the binding site of COX-2 indicated that the p-MeSO2 COX-2 pharmacophore group on the C-2 phenyl ring is oriented in the vicinity of the COX-2 secondary pocket (Arg(513), Phe(518) and Val(523)) and the carboxylic acid substituent can interact with Ser(530). The structure activity data acquired indicate that the size and nature of the C-4 quinoline substituent are important for COX-2 inhibitory activity. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.12.060

文献信息

• Design, synthesis and biological evaluation of new 2,3-diarylquinoline derivatives as selective cyclooxygenase-2 inhibitors
  作者：Razieh Ghodsi、Afshin Zarghi、Bahram Daraei、Mehdi Hedayati

  DOI：10.1016/j.bmc.2009.12.060

  日期：2010.2

  A new group of 2,3-diarylquinoline derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para-position of the C-2 phenyl ring were synthesized and evaluated as selective COX-2 inhibitors. In vitro COX-1/COX-2 structure-activity relationships were determined by varying the substituents on the C-4 quinoline ring. Among the 2,3-diarylquinolines, 2-(4-(methylsulfonyl) phenyl)-3-phenylquino-line-4-carboxylic acid (8) exhibited the highest potency and selectivity for COX-2 inhibitory activity (COX-2 IC50 = 0.07 mu M; selectivity index = 687.1) that was more selective than the reference drug celecoxib (COX-2 IC50 = 0.06 mu M; selectivity index = 405). A molecular modeling study where 8 was docked in the binding site of COX-2 indicated that the p-MeSO2 COX-2 pharmacophore group on the C-2 phenyl ring is oriented in the vicinity of the COX-2 secondary pocket (Arg(513), Phe(518) and Val(523)) and the carboxylic acid substituent can interact with Ser(530). The structure activity data acquired indicate that the size and nature of the C-4 quinoline substituent are important for COX-2 inhibitory activity. (C) 2010 Published by Elsevier Ltd.