N-(4-methoxybenzenesulfonyl)-N-tert-butoxycarbonylmethyl-O-benzyl-D-valine | 182319-86-4

• 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: N-(4-methoxybenzenesulfonyl)-N-tert-butoxycarbonylmethyl-O-benzyl-D-valine
• 英文别名: benzyl (2R)-2-[(4-methoxyphenyl)sulfonyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-3-methylbutanoate
• CAS: 182319-86-4
• 化学式: C₂₅H₃₃NO₇S
• 分子量: 491.606
• InChiKey: ILENOBUUWNNBHF-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(4-methoxybenzenesulfonyl)-N-tert-butoxycarbonylmethyl-O-benzyl-D-valine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 生成 N-(4-methoxybenzenesulfonyl)-N-tert-butoxycarbonylmethyl-D-valine
  参考文献：
  名称：

  Novel 1-Hydroxypiperazine-2,6-diones as New Leads in the Inhibition of Metalloproteinases

  摘要：

  New compounds containing a novel zinc-binding group (1-hydroxypiperazine-2,6-dione, HPD) have been identified as effective inhibitors of matrix metalloproteinases (MMPs), with activities in the nanomolar concentration range. That moiety seemed to bind the catalytic zinc ion of MMPs, revealing itself as a new potential substitute for the hydroxamate group in the next generation of metalloproteinase inhibitors. The X-ray crystal structure of 1b elucidated its 3D conformation and supramolecular packing in solid state. Theoretical procedures were used to investigate the binding mode of this class of compounds, within the active site of MMP13. A computational method involving docking and hybrid quantum mechanical and molecular mechanical (QM/MM) dynamic simulations was developed and applied. This study suggested that the HPD moiety binds bidentately to the catalytic zinc through its oxygen atoms. The final structure obtained will allow straightforward drug design approaches in view of further optimization and development of new MMP inhibitors bearing the HPD moiety.

  DOI：

  10.1021/jm200593b
• 作为产物：
  描述：

  D-缬氨酸 在 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 N-(4-methoxybenzenesulfonyl)-N-tert-butoxycarbonylmethyl-O-benzyl-D-valine
  参考文献：
  名称：

  Novel 1-Hydroxypiperazine-2,6-diones as New Leads in the Inhibition of Metalloproteinases

  摘要：

  New compounds containing a novel zinc-binding group (1-hydroxypiperazine-2,6-dione, HPD) have been identified as effective inhibitors of matrix metalloproteinases (MMPs), with activities in the nanomolar concentration range. That moiety seemed to bind the catalytic zinc ion of MMPs, revealing itself as a new potential substitute for the hydroxamate group in the next generation of metalloproteinase inhibitors. The X-ray crystal structure of 1b elucidated its 3D conformation and supramolecular packing in solid state. Theoretical procedures were used to investigate the binding mode of this class of compounds, within the active site of MMP13. A computational method involving docking and hybrid quantum mechanical and molecular mechanical (QM/MM) dynamic simulations was developed and applied. This study suggested that the HPD moiety binds bidentately to the catalytic zinc through its oxygen atoms. The final structure obtained will allow straightforward drug design approaches in view of further optimization and development of new MMP inhibitors bearing the HPD moiety.

  DOI：

  10.1021/jm200593b

文献信息

• Dual Inhibitors of Matrix Metalloproteinases and Carbonic Anhydrases: Iminodiacetyl-Based Hydroxamate−Benzenesulfonamide Conjugates
  作者：Sérgio M. Marques、Elisa Nuti、Armando Rossello、Claudiu T. Supuran、Tiziano Tuccinardi、Adriano Martinelli、M. Amélia Santos

  DOI：10.1021/jm800964f

  日期：2008.12.25

  Matrix metalloproteinases (MMPs) and carbonic anhydrases (CAs) are two classes of zinc enzymes with different roles and catalytic targets, such as the degradation of most of the extracellular matrix (ECM) proteins and the regulation of the CO2/HCO3- equilibrium in the cells, respectively. Both families have isoforms which were proved to be involved in several stages of carcinogenic processes, and so the selective inhibition of these enzymes might be of interest in cancer therapy. We report herein the design, synthesis, and in vitro evaluation of a series Of Compounds possessing the iminodiacetic acid as the main backbone and two functional groups attached, namely, the hydroxamic acid and the arylsulfonamide (ArSO2NH2) moieties, to enable the inhibition of MMPs and CAs, respectively. These compounds were demonstrated to strongly inhibit both MMPs and CAs, some of them from the nanomolar to subnanomolar range. Furthermore, a docking study for MMPs was reported for the most promising compound in order to investigate its binding interactions with the different MMPs.
• Novel 1-Hydroxypiperazine-2,6-diones as New Leads in the Inhibition of Metalloproteinases
  作者：Sérgio M. Marques、Tiziano Tuccinardi、Elisa Nuti、Salvatore Santamaria、Vânia André、Armando Rossello、Adriano Martinelli、M. Amélia Santos

  DOI：10.1021/jm200593b

  日期：2011.12.22

  New compounds containing a novel zinc-binding group (1-hydroxypiperazine-2,6-dione, HPD) have been identified as effective inhibitors of matrix metalloproteinases (MMPs), with activities in the nanomolar concentration range. That moiety seemed to bind the catalytic zinc ion of MMPs, revealing itself as a new potential substitute for the hydroxamate group in the next generation of metalloproteinase inhibitors. The X-ray crystal structure of 1b elucidated its 3D conformation and supramolecular packing in solid state. Theoretical procedures were used to investigate the binding mode of this class of compounds, within the active site of MMP13. A computational method involving docking and hybrid quantum mechanical and molecular mechanical (QM/MM) dynamic simulations was developed and applied. This study suggested that the HPD moiety binds bidentately to the catalytic zinc through its oxygen atoms. The final structure obtained will allow straightforward drug design approaches in view of further optimization and development of new MMP inhibitors bearing the HPD moiety.