t-butyl (4-(4-((dimethylcarbamoyl)thio)phenoxy)-2-(methoxymethoxy)phenyl)carbamate | 1333379-27-3

• 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: t-butyl (4-(4-((dimethylcarbamoyl)thio)phenoxy)-2-(methoxymethoxy)phenyl)carbamate
• 英文别名: tert-butyl N-[4-[4-(dimethylcarbamoylsulfanyl)phenoxy]-2-(methoxymethoxy)phenyl]carbamate
• CAS: 1333379-27-3
• 化学式: C₂₂H₂₈N₂O₆S
• 分子量: 448.54
• InChiKey: TVXSTETXKRSIKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  t-butyl (4-(4-((dimethylcarbamoyl)thio)phenoxy)-2-(methoxymethoxy)phenyl)carbamate 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 t-butyl (2-(methoxymethoxy)-4-(4-((oxiran-2-ylmethyl)thio)phenoxy)phenyl)-carbamate
  参考文献：
  名称：

  Selective Water-Soluble Gelatinase Inhibitor Prodrugs

  摘要：

  SB-3CT (1), a selective and potent thiirane-based gelatinase inhibitor, is effective in animal models of cancer metastasis and stroke; however, it is limited by poor aqueous solubility and extensive metabolism. We addressed these issues by blocking the primary site of metabolism and capitalizing on a prodrug strategy to achieve >5000-fold increased solubility. The amide prodrugs were quantitatively hydrolyzed in human blood to a potent gelatinase inhibitor, ND-322 (3). The arginyl amide prodrug (ND-478, 5d) was metabolically stable in mouse, rat, and human liver microsomes. Both 5d and 3 were nonmutagenic in the Ames II mutagenicity assay. The prodrug 5d showed moderate clearance of 0.0582 L/min/kg, remained mostly in the extracellular fluid compartment (Vd = 0.0978 L/kg), and had a terminal half-life of >4 h. The prodrug 5d had superior pharmacokinetic properties than those of 3, making the thiirane class of selective gelatinase inhibitors suitable for intravenous administration in the treatment of acute gelatinase-dependent diseases.

  DOI：

  10.1021/jm200566e
• 作为产物：
  描述：

  5-氟-2-硝基苯酚 在 铁粉 、 sodium hydride 、 氯化铵 、 caesium carbonate 、 三乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 t-butyl (4-(4-((dimethylcarbamoyl)thio)phenoxy)-2-(methoxymethoxy)phenyl)carbamate
  参考文献：
  名称：

  GELATINASE INHIBITORS AND PRODRUGS

  摘要：

  这项发明提供了用于治疗受基质金属蛋白酶（MMPs）调节的疾病、疾病或病况的化合物、组合物和方法。疾病、疾病或病况可以包括中风、神经系统疾病或眼科疾病等。治疗可以包括给予本文描述的化合物或组合物，从而提供在体内代谢为活性MMP抑制剂的前体化合物。MMP抑制可以是选择性抑制，例如对MMP-2、MMP-9和/或MMP-14的选择性抑制。因此，该发明提供了根据本文描述的公式的非致突变的前体化合物，该化合物在体内给予后导致MMP的抑制。

  公开号：

  US20130052184A1

文献信息

• Gelatinase inhibitors and prodrugs
  申请人：Chang Mayland

  公开号：US08937151B2

  公开（公告）日：2015-01-20

  The invention provides compounds, compositions, and methods for the treatment of diseases, disorders, or conditions that are modulated by matrix metalloproteinases (MMPs). The disease, disorder, or condition can include, for example, stroke, neurological disorders, or ophthalmological disorders. The treatment can include administering a compound or composition described herein, thereby providing a prodrug compound that metabolizes to an active MMP inhibitor in vivo. The MMP inhibition can be selective inhibition, for example, selective inhibition of MMP-2, MMP-9, and/or MMP-14. Thus, the invention provides non-mutagenic prodrug compounds of the formulas described herein that result in the inhibition of MMPs upon in vivo administration.

  本发明提供了化合物、组合物和方法，用于治疗受基质金属蛋白酶（MMPs）调节的疾病、障碍或病况。该疾病、障碍或病况可以包括中风、神经障碍或眼科障碍等。治疗可以包括给予本文所述的化合物或组合物，从而提供在体内代谢成活性MMP抑制剂的前药化合物。MMP抑制可以是选择性抑制，例如，选择性抑制MMP-2、MMP-9和/或MMP-14。因此，本发明提供了在体内给药后导致MMP抑制的本文所述公式的非诱变前药化合物。
• [EN] GELATINASE INHIBITORS AND PRODRUGS<br/>[FR] INHIBITEURS DE LA GÉLATINASE ET PROMÉDICAMENTS
  申请人：UNIV NOTRE DAME DU LAC

  公开号：WO2011109767A2

  公开（公告）日：2011-09-09

  The invention provides compounds, compositions, and methods for the treatment of diseases, disorders, or conditions that are modulated by matrix metalloproteinases (MMPs). The disease, disorder, or condition can include, for example, stroke, neurological disorders, or ophthalmological disorders. The treatment can include administering a compound or composition described herein, thereby providing a prodrug compound that metabolizes to an active MMP inhibitor in vivo. The MMP inhibition can be selective inhibition, for example, selective inhibition of MMP-2, MMP-9, and/or MMP-14. Thus, the invention provides non-mutagenic prodrug compounds of the formulas described herein that result in the inhibition of MMPs upon in vivo administration.