4-(Tert-butylsulfamoyl)benzoyl chloride | 918824-05-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(Tert-butylsulfamoyl)benzoyl chloride
• CAS: 918824-05-2
• 化学式: C₁₁H₁₄ClNO₃S
• 分子量: 275.756
• InChiKey: IYHGENOINIQHHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(Tert-butylsulfamoyl)benzoyl chloride 在 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 4.0h， 生成 4-(1-(4-bromophenyl)-3-mercapto-1H-1,2,4-triazol-5-yl)-N-(tert-butyl)benzenesulfonamide
  参考文献：
  名称：

  1,5-二芳基-1,2,4-三唑衍生物作为选择性环氧化酶-2抑制剂的设计、合成和生物学评价

  摘要：

  合成了一系列 1,5-二芳基-1,2,4-三唑衍生物，并评估其作为环氧合酶-2 (COX-2) 抑制剂。体内初步生物学测定结果表明，8种化合物5b、6b、6c、7c、8b、8d、9c和9d具有强效抗炎活性（P<0.01），而化合物6b、6c和9c则表现出强效抗炎活性（P<0.01）。显着效力。然后选择化合物 6c 进行进一步研究。在体外 COX 抑制试验中，化合物 6c 被鉴定为 COX-2 的有效选择性抑制剂（COX-2 IC50 = 0.37 µM；SI = 0.018），与塞来昔布（COX-2 IC50 = 0.26 µM；SI）等效= 0.015）。在大鼠角叉菜胶诱导的爪水肿试验中，6c 在以 15 mg/kg 口服给药后 2 小时表现出中等抗炎活性（炎症抑制 35%）。

  DOI：

  10.1002/ardp.200900227

文献信息

• Discovery of potential anti-inflammatory drugs: diaryl-1,2,4-triazoles bearing N-hydroxyurea moiety as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase
  作者：Bo Jiang、Xiaojing Huang、Hequan Yao、Jieyun Jiang、Xiaoming Wu、Siyi Jiang、Qiujuan Wang、Tao Lu、Jinyi Xu

  DOI：10.1039/c3ob41936c

  日期：——

  A series of hybrids from diaryl-1,2,4-triazole and hydroxamic acid or N-hydroxyurea were synthesized and evaluated as novel anti-inflammatory agents. The biological data showed that (i) all the compounds showed dual COX-2/5-LOX inhibitory activities in vitro, and 15e showed optimal inhibitory activities (COX-2: IC50 = 0.15 μM, 5-LOX: IC50 = 0.85 μM), (ii) 15e selectively inhibited COX-2 relative to COX-1 with selectivity index (SI = 0.012) comparable to celecoxib (SI = 0.015), (iii) 15e exhibited potent anti-inflammatory activity (inhibition: 54.1%) which was comparable to the reference drug celecoxib (inhibition: 46.7%) in a xylene-induced ear edema assay, and (iv) 15e displayed promising analgesic activity in acetic acid-induced writhing response and hot-plate assay. Finally, a molecular modeling study revealed the binding interactions of 15e with COX-2 and 5-LOX. Our findings suggest that 15e may be a promising anti-inflammatory agent for further evaluation.

  研究人员合成了一系列由二芳基-1,2,4-三唑和羟肟酸或 N-羟基脲组成的混合物，并将其作为新型抗炎剂进行了评估。生物数据显示：(i) 所有化合物在体外均显示出 COX-2/5-LOX 双重抑制活性，其中 15e 显示出最佳抑制活性（COX-2：IC50 = 0.15 μM，5-LOX：IC50 = 0.85 μM）；(ii) 相对于 COX-1，15e 选择性地抑制 COX-2，其选择性指数（SI = 0.012）与塞来昔布（SI = 0.(iii)在二甲苯诱导的耳部水肿试验中，15e 表现出强大的抗炎活性（抑制率：54.1%），与参考药物塞来昔布（抑制率：46.7%）相当；(iv)在醋酸诱导的蠕动反应和热板试验中，15e 表现出良好的镇痛活性。最后，分子建模研究揭示了 15e 与 COX-2 和 5-LOX 的结合相互作用。我们的研究结果表明，15e 可能是一种很有前景的抗炎药物，值得进一步评估。
• Discovery of novel hybrids of diaryl-1,2,4-triazoles and caffeic acid as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase for cancer therapy
  作者：Hao Cai、Xiaojing Huang、Shengtao Xu、Hao Shen、Pengfei Zhang、Yue Huang、Jieyun Jiang、Yijun Sun、Bo Jiang、Xiaoming Wu、Hequan Yao、Jingyi Xu

  DOI：10.1016/j.ejmech.2015.11.013

  日期：2016.1

  Inflammation plays a key role in cancer initiation and propagation. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), two important enzymes in inflammatory responses are up-regulated in various tumor types. Dual inhibition of COX-2 and 5-LOX constitutes a rational concept for the design of more efficacious anti-tumor agents with an improved safety profile. We have previously reported a series of diaryl-1,2,4-triazole derivatives as selective COX-2 inhibitors. Herein, we hybridized the diaryl-1,2,4triazoles with caffeic acid (CA) which was reported to display 5-LOX inhibitory and anti-tumor activities, affording a novel class of COX-2/5-LOX dual inhibitors as anti-tumor drug candidates. Most of these compounds exhibited potent COX-2/5-LOX inhibitory and antiproliferative activities in vitro. And the most potent compound 22b could significantly inhibit tumor growth in vivo. Furthermore, mechanistic investigation showed that the representative compound 15c blocked cell cycle in G2 phase and induced apoptosis in human non-small cell lung cancer A549 cells in a dose-dependent manner. Our preliminary investigation results would provide new clues for the cancer theatment with COX-2/5-LOX dual inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.