4-(4-Fluorophenyl)-5-(4-methylsulfanylphenyl)-1,3-dihydroimidazole-2-thione | 97060-27-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-Fluorophenyl)-5-(4-methylsulfanylphenyl)-1,3-dihydroimidazole-2-thione
• CAS: 97060-27-0
• 化学式: C₁₆H₁₃FN₂S₂
• 分子量: 316.423
• InChiKey: MRNIVYXKZJASKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-Fluorophenyl)-5-(4-methylsulfanylphenyl)-1,3-dihydroimidazole-2-thione 、 碘乙烷 在 sodium persulfate 作用下， 以 甲醇 、 四氢呋喃 、 水 为溶剂， 反应 18.0h， 以63%的产率得到2-ethylsulfonyl-5-(4-fluorophenyl)-4-(4-methylsulfonylphenyl)-1H-imidazole
  参考文献：
  名称：

  Synthesis, cyclooxygenase inhibitory effects, and molecular modeling study of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and -2-alkylsulfonyl-1 H -imidazole derivatives

  摘要：

  A series of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and 2-alkylsulfonyl-1H-imidazole derivatives were synthesized. All compounds were tested in human blood assay to determine COX-1 and COX-2 inhibitory potency and selectivity. Among the synthesized compounds, 2-alkylthio series were more potent and selective than 2-sulfonylalkyl derivatives. In molecular modeling, interaction of 2-sulfonylalkyl moiety with Arg120 in COX-1 and an extra hydrogen bond with Tyr341 in COX-2 increased the residence time of ligands in the active site in 2-sulfonylalkyl and 2-alkylthio analogs, respectively. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.058
• 作为产物：
  描述：

  4-氟苯乙酸 在 磷酸 、 溴 、 sodium methylate 、 溶剂黄146 、 三氟乙酸酐 作用下， 以 甲醇 、 正丁醇 为溶剂， 生成 4-(4-Fluorophenyl)-5-(4-methylsulfanylphenyl)-1,3-dihydroimidazole-2-thione
  参考文献：
  名称：

  Synthesis, cyclooxygenase inhibitory effects, and molecular modeling study of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and -2-alkylsulfonyl-1 H -imidazole derivatives

  摘要：

  A series of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and 2-alkylsulfonyl-1H-imidazole derivatives were synthesized. All compounds were tested in human blood assay to determine COX-1 and COX-2 inhibitory potency and selectivity. Among the synthesized compounds, 2-alkylthio series were more potent and selective than 2-sulfonylalkyl derivatives. In molecular modeling, interaction of 2-sulfonylalkyl moiety with Arg120 in COX-1 and an extra hydrogen bond with Tyr341 in COX-2 increased the residence time of ligands in the active site in 2-sulfonylalkyl and 2-alkylthio analogs, respectively. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.058

文献信息

• Preparation, antiarthritic and analgesic activity of 4,5-diaryl-2-(substituted thio)-1H-imidazoles and their sulfoxides and sulfones
  作者：Thomas R. Sharpe、Saul C. Cherkofsky、Walter E. Hewes、Dewey H. Smith、Walter A. Gregory、Stephen B. Haber、Michael R. Leadbetter、Joel G. Whitney

  DOI：10.1021/jm00147a011

  日期：1985.9

  A series of 4,5-diaryl-2-(substituted thio)-1H-imidazoles was synthesized and evaluated as antiinflammatory and analgesic agents in the rat adjuvant induced arthritis assay and the mouse phenyl-p-benzoquinone writhing (PQW) assay. Several analogues were found to be more potent than phenylbutazone and indomethacin. Structure-activity relationships are discussed. One of the compounds, 4,5-bis(4-fluorophenyl)-2-[(1

  合成了一系列的4,5-二芳基-2-（取代硫代）-1H-咪唑，并在大鼠佐剂诱导的关节炎试验和小鼠苯基-对苯醌扭曲（PQW）试验中用作抗炎和镇痛药。发现几种类似物比苯基丁a和消炎痛更有效。讨论了构效关系。发现其中一种化合物4,5-双（4-氟苯基）-2-[（（1,1,2,2-四氟乙基）-磺酰基] -1H-咪唑（8d，tiflamizole）是在大鼠佐剂诱导的关节炎试验中具有消炎痛的作用，目前正在作为抗关节炎药进行临床试验。
• Synthesis and SAR study of 4,5-diaryl-1H-imidazole-2(3H)-thione derivatives, as potent 15-lipoxygenase inhibitors
  作者：Amir Assadieskandar、Mohsen Amini、Marjan Salehi、Hamid Sadeghian、Maliheh Alimardani、Amirhossein Sakhteman、Hamid Nadri、Abbas Shafiee

  DOI：10.1016/j.bmc.2012.09.050

  日期：2012.12

  A series of 4,5-diaryl-1H-imidazole-2(3H)-thione was synthesized and their inhibitory potency against soybean 15-lipoxygenase and free radical scavenging activities were determined. Compound 11 showed the best IC50 for 15-LOX inhibition (IC50 = 4.7 mu M) and free radical scavenging activity (IC50 = 14 mu M). Methylation of SH at C-2 position of imidazole has dramatically decreased the 15-LOX inhibition and radical scavenging activity as it can be observed in the inactive compound 14 (IC50 >250 mu M). Structure activity similarity (SAS) showed that the most important chemical modification in this series was methylation of SH group and Docking studies revealed a proper orientation for SH group towards Fe core of the 15-LOX active site. Therefore it was concluded that iron chelating could be a possible mechanism for enzyme inhibition in this series of compounds. (C) 2012 Elsevier Ltd. All rights reserved.
• SHARPE, T. R.;CHERKOFSKY, S. C.;HEWES, W. E.;SMITH, D. H.;GREGORY, W. A.;+, J. MED. CHEM., 1985, 28, N 9, 1188-1194
  作者：SHARPE, T. R.、CHERKOFSKY, S. C.、HEWES, W. E.、SMITH, D. H.、GREGORY, W. A.、+

  DOI：——

  日期：——