tert-butyl 2-(5-bromo-N-isopropoxythiophene-2-sulfonamido)acetate | 1178858-75-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 2-(5-bromo-N-isopropoxythiophene-2-sulfonamido)acetate
• 英文别名: Tert-butyl 2-[(5-bromothiophen-2-yl)sulfonyl-propan-2-yloxyamino]acetate
• CAS: 1178858-75-7
• 化学式: C₁₃H₂₀BrNO₅S₂
• 分子量: 414.342
• InChiKey: KPIYCEJNDMLCAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(5-bromo-N-isopropoxythiophene-2-sulfonamido)acetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以83%的产率得到2-(5-bromo-N-isopropoxythiophene-2-sulfonamido)acetic acid
  参考文献：
  名称：

  Synthesis, experimental evaluation and molecular modelling of hydroxamate derivatives as zinc metalloproteinase inhibitors

  摘要：

  Enzymes of the M4 family of zinc-metalloproteinases are virulence factors secreted from gram-positive or gram-negative bacteria, and putative drug targets in the treatment of bacterial infections. In order to have a therapeutic value such inhibitors should not interfere with endogenous zinc-metalloproteinases. In the present study we have synthesised a series of hydroxamate derivatives and validated the compounds as inhibitors of the M4 enzymes thermolysin and pseudolysin, and the endogenous metalloproteinases ADAM-17, MMP-2 and MMP-9 using experimental binding studies and molecular modelling. In general, the compounds are stronger inhibitors of the MMPs than of the M4 enzymes, however, an interesting exception is LM2. The compounds bound stronger to pseudolysin than to thermolysin, and the molecular modelling studies showed that occupation of the S-2' subpocket by an aromatic group is favourable for strong interactions with pseudolysin. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.019
• 作为产物：
  描述：

  溴乙酸叔丁酯 、 5-bromo-N-isopropoxythiophene-2-sulfonamide 在 四丁基硫酸氢铵 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 以79.4%的产率得到tert-butyl 2-(5-bromo-N-isopropoxythiophene-2-sulfonamido)acetate
  参考文献：
  名称：

  N-O-Isopropyl Sulfonamido-Based Hydroxamates: Design, Synthesis and Biological Evaluation of Selective Matrix Metalloproteinase-13 Inhibitors as Potential Therapeutic Agents for Osteoarthritis

  摘要：

  Matrix metalloproteinase-13 (MMP-13) is a key enzyme implicated in the degradation of the extracellular matrix in osteoarthritis (OA). For this reason, MMP-13 synthetic inhibitors arc being sought as potential therapeutic agents to prevent cartilage degradation and to halt the progression of OA. Herein, we report the synthesis and in vitro evaluation of a new series of selective MMP-13 inhibitors possessing an arylsulfonamidic scaffold. Among these potential inhibitors, a very promising compound was discovered exhibiting nanomolar activity for MMP-13 and was highly selective for this enzyme compared to MMP-1, -14, and TACE. This compound acted as a slow-binding inhibitor of MMP-13 and was demonstrated to be effective in an in vitro Collagen assay and in a model of cartilage degradation. Furthermore, a docking study was conducted for this compound in order to investigate its binding interactions with MMP-13 and the reasons for its selectivity toward MMP-13 versus other MMPs.

  DOI：

  10.1021/jm900261f

文献信息

• <i>N-O-</i>Isopropyl Sulfonamido-Based Hydroxamates: Design, Synthesis and Biological Evaluation of Selective Matrix Metalloproteinase-13 Inhibitors as Potential Therapeutic Agents for Osteoarthritis
  作者：Elisa Nuti、Francesca Casalini、Stanislava I. Avramova、Salvatore Santamaria、Giovanni Cercignani、Luciana Marinelli、Valeria La Pietra、Ettore Novellino、Elisabetta Orlandini、Susanna Nencetti、Tiziano Tuccinardi、Adriano Martinelli、Ngee-Han Lim、Robert Visse、Hideaki Nagase、Armando Rossello

  DOI：10.1021/jm900261f

  日期：2009.8.13

  Matrix metalloproteinase-13 (MMP-13) is a key enzyme implicated in the degradation of the extracellular matrix in osteoarthritis (OA). For this reason, MMP-13 synthetic inhibitors arc being sought as potential therapeutic agents to prevent cartilage degradation and to halt the progression of OA. Herein, we report the synthesis and in vitro evaluation of a new series of selective MMP-13 inhibitors possessing an arylsulfonamidic scaffold. Among these potential inhibitors, a very promising compound was discovered exhibiting nanomolar activity for MMP-13 and was highly selective for this enzyme compared to MMP-1, -14, and TACE. This compound acted as a slow-binding inhibitor of MMP-13 and was demonstrated to be effective in an in vitro Collagen assay and in a model of cartilage degradation. Furthermore, a docking study was conducted for this compound in order to investigate its binding interactions with MMP-13 and the reasons for its selectivity toward MMP-13 versus other MMPs.
• Synthesis, experimental evaluation and molecular modelling of hydroxamate derivatives as zinc metalloproteinase inhibitors
  作者：Stian Sjøli、Elisa Nuti、Caterina Camodeca、Irina Bilto、Armando Rossello、Jan-Olof Winberg、Ingebrigt Sylte、Olayiwola A. Adekoya

  DOI：10.1016/j.ejmech.2015.11.019

  日期：2016.1

  Enzymes of the M4 family of zinc-metalloproteinases are virulence factors secreted from gram-positive or gram-negative bacteria, and putative drug targets in the treatment of bacterial infections. In order to have a therapeutic value such inhibitors should not interfere with endogenous zinc-metalloproteinases. In the present study we have synthesised a series of hydroxamate derivatives and validated the compounds as inhibitors of the M4 enzymes thermolysin and pseudolysin, and the endogenous metalloproteinases ADAM-17, MMP-2 and MMP-9 using experimental binding studies and molecular modelling. In general, the compounds are stronger inhibitors of the MMPs than of the M4 enzymes, however, an interesting exception is LM2. The compounds bound stronger to pseudolysin than to thermolysin, and the molecular modelling studies showed that occupation of the S-2' subpocket by an aromatic group is favourable for strong interactions with pseudolysin. (C) 2015 Elsevier Masson SAS. All rights reserved.