4-(5-(3-hydroxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide | 1335246-17-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(5-(3-hydroxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
• 英文别名: 4-[5-(3-Hydroxy-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-benzenesulfonamide；4-[5-(3-hydroxyphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
• CAS: 1335246-17-7
• 化学式: C₁₆H₁₂F₃N₃O₃S
• 分子量: 383.351
• InChiKey: YMVRMYZEYUEFRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 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：
  107
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(5-(3-hydroxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide 、 乙酰氯 在 三乙胺 作用下， 以 乙醚 为溶剂， 以43%的产率得到1-(4-aminosulfonylphenyl)-3-trifluoromethyl-5-(3-acetoxyphenyl)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
• 作为产物：
  描述：

  在 乙硫醇钠 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 4-(5-(3-hydroxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
  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

• Synthesis and preliminary in vitro biological evaluation of new carbon-11-labeled celecoxib derivatives as candidate PET tracers for imaging of COX-2 expression in cancer
  作者：Mingzhang Gao、Min Wang、Kathy D. Miller、Qi-Huang Zheng

  DOI：10.1016/j.ejmech.2011.05.024

  日期：2011.9

  The enzyme cyclooxygenase-2 (COX-2) is overexpressed in a variety of malignant tumors. This study was designed to develop new radiotracers for imaging of COX-2 in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled celecoxib derivatives, [11C]4a–c and [11C]8a–d, were prepared by O-[11C] methylation of their corresponding precursors using [11C]CH3OTf under

  环氧合酶2（COX-2）酶在多种恶性肿瘤中过表达。这项研究旨在开发使用生物医学成像技术正电子发射断层扫描（PET）对癌症中的COX-2进行成像的新型放射性示踪剂。碳11标记的塞来昔布衍生物[ 11 C] 4a – c和[ 11 C] 8a – d是在碱性条件下，使用[ 11 C] CH 3 OTf通过其相应前体的O- [ 11 C]甲基化制备的。通过简化的固相萃取（SPE）方法分离得到52±2％（n  = 5）和57±3％（n = 5）基于[ 11 C] CO 2的放射化学产率，其衰变校正为轰击结束（EOB）。从EOB开始的总合成时间为23分钟，放射化学纯度> 99％，合成结束时的比活（EOS）为277.5±92.5 GBq /μmol（n  = 5）。已知化合物塞来昔布（4d），4a和4c阻断COX-2的IC 50值分别为40、290和8 nM，体外生物学分析的初步发现表明合成的新化合物4b和8a