4-[(2-氯-4-氟苯基)甲氧基]苯磺酰氯 | 1036509-25-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-[(2-氯-4-氟苯基)甲氧基]苯磺酰氯
• 英文名称: 4-(2-chloro-4-fluorobenzyloxy)benzene-1-sulfonyl chloride
• 英文别名: 4-((2-chloro-4-fluorobenzyl)oxy)benzene-1-sulphonyl chloride；4-((2-Chloro-4-fluorobenzyl)oxy)benzene-1-sulfonyl chloride；4-[(2-chloro-4-fluorophenyl)methoxy]benzenesulfonyl chloride
• CAS: 1036509-25-7
• 化学式: C₁₃H₉Cl₂FO₃S
• 分子量: 335.183
• InChiKey: IGPPZHPZZWJTNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2909309090

反应信息

• 作为反应物：
  描述：

  4-[(2-氯-4-氟苯基)甲氧基]苯磺酰氯 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 2-[[4-[(2-chloro-4-fluorophenyl)methoxy]phenyl]sulfonylamino]-N-hydroxyacetamide
  参考文献：
  名称：

  Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation

  摘要：

  Aggrecanases, in particular aggrecanase-2 (ADAMTS-5), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis. For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibitors able to slow down or halt the progression of osteoarthritis. We report herein the synthesis and biological evaluation of a series of arylsulfonamido-based hydroxamates as aggrecanase inhibitors. Compound 18 was found to have a nanomolar activity for ADAMTS-5, ADAMTS-4 and MMP-13 and high selectivity over MMP-1 and MMP-14. Furthermore, this compound proved to be effective in blocking ex vivo cartilage degradation without having effect on cell cytotoxicity. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.12.058
• 作为产物：
  描述：

  sodium p-hydroxybenzenesulfonate 在 草酰氯 、 sodium hydroxide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 48.2h， 生成 4-[(2-氯-4-氟苯基)甲氧基]苯磺酰氯
  参考文献：
  名称：

  Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation

  摘要：

  Aggrecanases, in particular aggrecanase-2 (ADAMTS-5), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis. For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibitors able to slow down or halt the progression of osteoarthritis. We report herein the synthesis and biological evaluation of a series of arylsulfonamido-based hydroxamates as aggrecanase inhibitors. Compound 18 was found to have a nanomolar activity for ADAMTS-5, ADAMTS-4 and MMP-13 and high selectivity over MMP-1 and MMP-14. Furthermore, this compound proved to be effective in blocking ex vivo cartilage degradation without having effect on cell cytotoxicity. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.12.058

文献信息

• Development of a fluorogenic ADAMTS-7 substrate
  作者：Salvatore Santamaria、Frederic Buemi、Elisa Nuti、Doretta Cuffaro、Elena De Vita、Tiziano Tuccinardi、Armando Rossello、Steven Howell、Shahid Mehmood、Ambrosius P. Snijders、Rens de Groot

  DOI：10.1080/14756366.2021.1983808

  日期：2021.1.1

  reported so far. Screening of inhibitors has been hindered by the lack of a suitable peptide substrate and, consequently, a convenient activity assay. Here we describe the first fluorescence resonance energy transfer (FRET) substrate for ADAMTS-7, ATS7FP7. ATS7FP7 was used to measure inhibition constants for the endogenous ADAMTS-7 inhibitor, TIMP-4, as well as two hydroxamate-based zinc chelating inhibitors

   抽象的 细胞外蛋白酶 ADAMTS-7 已被确定为动脉粥样硬化和冠状动脉疾病 (CAD) 等相关疾病的潜在治疗靶点。但迄今为止，ADAMTS-7抑制剂尚未见报道。由于缺乏合适的肽底物，因此阻碍了抑制剂的筛选，因此也阻碍了方便的活性测定。在这里，我们描述了 ADAMTS-7 的第一个荧光共振能量转移 (FRET) 底物 ATS7FP7。 ATS7FP7 用于测量内源性 ADAMTS-7 抑制剂 TIMP-4 以及两种异羟肟酸锌螯合抑制剂的抑制常数。这些抑制常数与我们的 SDS-PAGE 测定获得的 IC 50值非常匹配，该测定使用潜在 TGF-β 结合蛋白 4 (LTBP4S-A) 的 N 末端片段作为底物。我们的新型荧光底物 ATS7FP7 适用于 ADAMTS-7 抑制剂的高通量筛选，从而加速旨在抑制 ADAMTS-7 作为动脉粥样硬化和 CAD 等心血管疾病的新型治疗方法的转化研究。
• Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation
  作者：Elisa Nuti、Salvatore Santamaria、Francesca Casalini、Kazuhiro Yamamoto、Luciana Marinelli、Valeria La Pietra、Ettore Novellino、Elisabetta Orlandini、Susanna Nencetti、Anna Maria Marini、Silvia Salerno、Sabrina Taliani、Federico Da Settimo、Hideaki Nagase、Armando Rossello

  DOI：10.1016/j.ejmech.2012.12.058

  日期：2013.4

  Aggrecanases, in particular aggrecanase-2 (ADAMTS-5), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis. For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibitors able to slow down or halt the progression of osteoarthritis. We report herein the synthesis and biological evaluation of a series of arylsulfonamido-based hydroxamates as aggrecanase inhibitors. Compound 18 was found to have a nanomolar activity for ADAMTS-5, ADAMTS-4 and MMP-13 and high selectivity over MMP-1 and MMP-14. Furthermore, this compound proved to be effective in blocking ex vivo cartilage degradation without having effect on cell cytotoxicity. (C) 2013 Elsevier Masson SAS. All rights reserved.