{2-[4-(5-para-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonylamino]ethyl}carbamic acid tert-butyl ester | 1416368-39-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: {2-[4-(5-para-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonylamino]ethyl}carbamic acid tert-butyl ester
• 英文别名: {2-[4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonylamino]ethyl}carbamic acid tert-butyl ester；tert-butyl N-[2-[[4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonylamino]ethyl]carbamate
• CAS: 1416368-39-2
• 化学式: C₂₄H₂₇F₃N₄O₄S
• 分子量: 524.564
• InChiKey: UJNFJZSOIVJDRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  {2-[4-(5-para-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonylamino]ethyl}carbamic acid tert-butyl ester 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.08h， 生成 5-(dimethylamino)-N-[2-[[4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonylamino]ethyl]naphthalene-1-sulfonamide
  参考文献：
  名称：

  Hybrid fluorescent conjugates of COX-2 inhibitors: Search for a COX-2 isozyme imaging cancer biomarker

  摘要：

  The observation that the cyclooxygenase-2 (COX-2) isozyme is over-expressed in multiple types of cancer, relative to that in adjacent non-cancerous tissue, prompted this investigation to prepare a group of hybrid fluorescent conjugates wherein the COX inhibitors ibuprofen, (S)-naproxen, acetyl salicylic acid, a chlororofecoxib analog and celecoxib were coupled via a linker group to an acridone, dansyl or rhodamine B fluorophore. Within this group of compounds, the ibuprofen-acridone conjugate (10) showed potent and selective COX-2 inhibition (COX-2 IC50 = 0.67 mu M; SI = 110.6), but its fluorescence emission (lambda(em) = 417, 440 nm) was not suitable for fluorescent imaging of cancer cells that over-express the COX-2 isozyme. In comparison, the celecoxib-dansyl conjugate (25) showed a slightly lower COX-2 potency and selectivity (COX-2 IC50 = 1.1 mu M; SI > 90) than the conjugate 10, and it possesses a better fluorescence emission (lambda(em) = 500 nm). Ultimately, a celecoxib-rhodamine B conjugate (28) that exhibited moderate COX-2 potency and selectivity (COX-2 IC50 = 3.9 mu M; SI > 25) having the best fluorescence emission (lambda(em) = 580 nm) emerged as the most promising biomarker for fluorescence imaging using a colon cancer cell line that over-expresses the COX-2 isozyme. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.131
• 作为产物：
  描述：

  N-叔丁氧羰基-1,2-乙二胺 、 4-[5-(4-甲基苯基)-3-三氟甲基-1H-吡唑-1-基]苯磺酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以67%的产率得到{2-[4-(5-para-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonylamino]ethyl}carbamic acid tert-butyl ester
  参考文献：
  名称：

  基于Celecoxib–NBD的18F标签放射性示踪剂的设计，合成和评估，用于环氧合酶2（COX-2）的正电子发射断层扫描（PET）成像

  摘要：

  根据先前报道的荧光COX-2成像剂celecoxib-NBD（3； NBD = 7-硝基-硝基苯并呋喃），设计和合成了一系列新型的含氟环氧合酶-2（COX-2）抑制剂。体外COX-1 / COX-2抑制的数据显示，ñ - （4-氟苄基）-4-（5- p -甲苯基-3-三氟甲基吡唑-1-基）苯磺酰胺（5 ; IC 50 = 0.36μ中号，SI > 277）和ñ -氟-4-（5- p -甲苯基-3-三氟甲基吡唑-1-基）苯磺酰胺（6 ; IC 50 = 0.24μ中号，SI> 416）是有效的和选择性COX-2抑制剂。化合物5选择使用短寿命的正电子发射器Fluor-18（18 F）进行放射性标记，并作为正电子发射断层扫描（PET）成像剂进行评估。使用人类结直肠癌模型HCA-7在体外和体内对Radiotracer [ 18 F] 5进行了分析。尽管放射性示踪剂对表达COX-2的HCA-7细胞的

  DOI：

  10.1002/cmdc.201500287

文献信息

• Fluorophore-Labeled Cyclooxygenase-2 Inhibitors for the Imaging of Cyclooxygenase-2 Overexpression in Cancer: Synthesis and Biological Studies
  作者：Atul Bhardwaj、Jatinder Kaur、Frank Wuest、Edward E. Knaus

  DOI：10.1002/cmdc.201300355

  日期：2014.1

  (COX‐2)‐specific fluorescent cancer biomarkers were synthesized by linking the anti‐inflammatory drugs ibuprofen, (S)‐naproxen, and celecoxib to the 7‐nitrobenzofurazan (NBD) fluorophore. In vitro COX‐1/COX‐2 inhibition studies indicated that all of these fluorescent conjugates are COX‐2 inhibitors (IC50 range: 0.19–23.0 μM) with an appreciable COX‐2 selectivity index (SI≥4.3–444). In this study the celecoxib–NBD

  通过将抗炎药布洛芬，（S）-萘普生和塞来昔布与7-硝基苯并呋喃山（NBD）荧光团连接，合成了一组特定于环氧合酶2（COX-2）的荧光癌生物标记。体外COX-1 / COX-2抑制的研究表明，所有这些荧光缀合物的是COX-2抑制剂（IC 50范围：0.19-23.0μ中号）与可感知的COX-2选择性指数（SI≥4.3-444）。在这项研究中，塞来昔布-NBD共轭N-（2-（（7-硝基苯并[ c ] [1,2,5]恶二唑-4-基）氨基）乙基）-4-（5-（对甲苯基）- 3-（三氟甲基）-1 H-吡唑-1-基）苯磺酰胺（14），其显示的最高COX-2抑制的效力和选择性（COX-2的IC 50 = 0.19μ中号;使用COX-SI = 443.6），被认定为即将发生的COX-2特异性的生物标记用于癌症的荧光成像2表达人类结肠癌细胞系（HCA-7）。
• Hybrid fluorescent conjugates of COX-2 inhibitors: Search for a COX-2 isozyme imaging cancer biomarker
  作者：Atul Bhardwaj、Jatinder Kaur、Sai Kiran Sharma、Zhangjian Huang、Frank Wuest、Edward E. Knaus

  DOI：10.1016/j.bmcl.2012.10.131

  日期：2013.1

  The observation that the cyclooxygenase-2 (COX-2) isozyme is over-expressed in multiple types of cancer, relative to that in adjacent non-cancerous tissue, prompted this investigation to prepare a group of hybrid fluorescent conjugates wherein the COX inhibitors ibuprofen, (S)-naproxen, acetyl salicylic acid, a chlororofecoxib analog and celecoxib were coupled via a linker group to an acridone, dansyl or rhodamine B fluorophore. Within this group of compounds, the ibuprofen-acridone conjugate (10) showed potent and selective COX-2 inhibition (COX-2 IC50 = 0.67 mu M; SI = 110.6), but its fluorescence emission (lambda(em) = 417, 440 nm) was not suitable for fluorescent imaging of cancer cells that over-express the COX-2 isozyme. In comparison, the celecoxib-dansyl conjugate (25) showed a slightly lower COX-2 potency and selectivity (COX-2 IC50 = 1.1 mu M; SI > 90) than the conjugate 10, and it possesses a better fluorescence emission (lambda(em) = 500 nm). Ultimately, a celecoxib-rhodamine B conjugate (28) that exhibited moderate COX-2 potency and selectivity (COX-2 IC50 = 3.9 mu M; SI > 25) having the best fluorescence emission (lambda(em) = 580 nm) emerged as the most promising biomarker for fluorescence imaging using a colon cancer cell line that over-expresses the COX-2 isozyme. (C) 2012 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Evaluation of an¹⁸F-Labeled Radiotracer Based on Celecoxib-NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase-2 (COX-2)
  作者：Jatinder Kaur、Ole Tietz、Atul Bhardwaj、Alison Marshall、Jenilee Way、Melinda Wuest、Frank Wuest

  DOI：10.1002/cmdc.201500287

  日期：2015.10

  cyclooxygenase‐2 (COX‐2) inhibitors was designed and synthesized based on the previously reported fluorescent COX‐2 imaging agent celecoxib–NBD (3; NBD=7‐nitrobenzofurazan). In vitro COX‐1/COX‐2 inhibitory data show that N‐(4‐fluorobenzyl)‐4‐(5‐p‐tolyl‐3‐trifluoromethylpyrazol‐1‐yl)benzenesulfonamide (5; IC50=0.36 μM, SI>277) and N‐fluoromethyl‐4‐(5‐p‐tolyl‐3‐trifluoromethylpyrazol‐1‐yl)benzenesulfonamide (6;

  根据先前报道的荧光COX-2成像剂celecoxib-NBD（3； NBD = 7-硝基-硝基苯并呋喃），设计和合成了一系列新型的含氟环氧合酶-2（COX-2）抑制剂。体外COX-1 / COX-2抑制的数据显示，ñ - （4-氟苄基）-4-（5- p -甲苯基-3-三氟甲基吡唑-1-基）苯磺酰胺（5 ; IC 50 = 0.36μ中号，SI > 277）和ñ -氟-4-（5- p -甲苯基-3-三氟甲基吡唑-1-基）苯磺酰胺（6 ; IC 50 = 0.24μ中号，SI> 416）是有效的和选择性COX-2抑制剂。化合物5选择使用短寿命的正电子发射器Fluor-18（18 F）进行放射性标记，并作为正电子发射断层扫描（PET）成像剂进行评估。使用人类结直肠癌模型HCA-7在体外和体内对Radiotracer [ 18 F] 5进行了分析。尽管放射性示踪剂对表达COX-2的HCA-7细胞的