1-(4-methylsulfonylphenyl)-3-trifluoromethyl-5-(2-acetoxy-4-methylphenyl)pyrazole | 1338216-29-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-methylsulfonylphenyl)-3-trifluoromethyl-5-(2-acetoxy-4-methylphenyl)pyrazole
• 英文别名: [5-Methyl-2-[2-(4-methylsulfonylphenyl)-5-(trifluoromethyl)pyrazol-3-yl]phenyl] acetate
• CAS: 1338216-29-7
• 化学式: C₂₀H₁₇F₃N₂O₄S
• 分子量: 438.427
• InChiKey: FEJHXMDTVILOGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  86.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-(2-甲氧基-4-甲基苯基)乙酮 在 Oxone 、 sodium methylate 、 三乙胺 、 乙硫醇钠 作用下， 以 甲醇 、 乙醚 、 乙醇 、 甲基叔丁基醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 67.25h， 生成 1-(4-methylsulfonylphenyl)-3-trifluoromethyl-5-(2-acetoxy-4-methylphenyl)pyrazole
  参考文献：
  名称：

  Isomeric acetoxy analogs of celecoxib and their evaluation as cyclooxygenase inhibitors

  摘要：

  A group of celecoxib analogs having a SO2NH2 (9a-f), or SO2Me (12a-f), COX-2 pharmacophore at the para-position of the N-1 phenyl ring in conjunction with a C-5 phenyl ring having a variety of substituents (4-, 3-, 2-OAc; 4-Me, 2-OAc, 4-Me, 3-OAc, 4-F,2-OAc) was synthesized for evaluation as cyclooxygenase (COX) inhibitors of the COX-1/COX-2 isozymes. Within this group of compounds, 1-(4-aminosulfonylphenyl)-3-trifluoromethyl-5-(2-acetoxy-4-fluorophenyl)pyrazole (9f) emerged as the most potent (COX-1 IC50 = 0.7 mu M; COX-2 IC50 = 0.015 mu M) and selective (COX-2 selectivity index = 47) inhibitor agent that exhibited good anti-inflammatory activity (ED50 = 42.3 mg/kg) which was lower than the reference drug celecoxib (ED50 = 10.8 mg/kg), but greater than ibuprofen (ED50 = 67.4 mg/kg) and aspirin (ED50 = 128.7 mg/kg). Molecular modeling studies for 9f showed that the SO2NH2 group assumes a position within the secondary pocket of the COX-2 active site wherein the SO2NH2 oxygen atom is hydrogen bonded to the H90 residue (2.90 angstrom), the SO2NH2 nitrogen atom forms a hydrogen bond with L352 (N center dot center dot center dot O = 2.80 angstrom ), and the acetyl group is positioned in the vicinity of the S530 residue where the acetyl oxygen atom undergoes hydrogen bonding to L531 (2.99 angstrom). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.053

文献信息

• Isomeric acetoxy analogs of celecoxib and their evaluation as cyclooxygenase inhibitors
  作者：M. Abdur Rahim、P.N. Praveen Rao、Atul Bhardwaj、Jatinder Kaur、Zhangjian Huang、Edward E. Knaus

  DOI：10.1016/j.bmcl.2011.08.053

  日期：2011.10

  A group of celecoxib analogs having a SO2NH2 (9a-f), or SO2Me (12a-f), COX-2 pharmacophore at the para-position of the N-1 phenyl ring in conjunction with a C-5 phenyl ring having a variety of substituents (4-, 3-, 2-OAc; 4-Me, 2-OAc, 4-Me, 3-OAc, 4-F,2-OAc) was synthesized for evaluation as cyclooxygenase (COX) inhibitors of the COX-1/COX-2 isozymes. Within this group of compounds, 1-(4-aminosulfonylphenyl)-3-trifluoromethyl-5-(2-acetoxy-4-fluorophenyl)pyrazole (9f) emerged as the most potent (COX-1 IC50 = 0.7 mu M; COX-2 IC50 = 0.015 mu M) and selective (COX-2 selectivity index = 47) inhibitor agent that exhibited good anti-inflammatory activity (ED50 = 42.3 mg/kg) which was lower than the reference drug celecoxib (ED50 = 10.8 mg/kg), but greater than ibuprofen (ED50 = 67.4 mg/kg) and aspirin (ED50 = 128.7 mg/kg). Molecular modeling studies for 9f showed that the SO2NH2 group assumes a position within the secondary pocket of the COX-2 active site wherein the SO2NH2 oxygen atom is hydrogen bonded to the H90 residue (2.90 angstrom), the SO2NH2 nitrogen atom forms a hydrogen bond with L352 (N center dot center dot center dot O = 2.80 angstrom ), and the acetyl group is positioned in the vicinity of the S530 residue where the acetyl oxygen atom undergoes hydrogen bonding to L531 (2.99 angstrom). (C) 2011 Elsevier Ltd. All rights reserved.