4-[4-(Thiiran-2-ylmethylsulfonyl)phenoxy]phenol | 915155-91-8

• 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-[4-(Thiiran-2-ylmethylsulfonyl)phenoxy]phenol
• CAS: 915155-91-8
• 化学式: C₁₅H₁₄O₄S₂
• 分子量: 322.406
• InChiKey: AHDPJKYOQXMDIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  97.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[4-(Thiiran-2-ylmethylsulfonyl)phenoxy]phenol 在 盐酸 、 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 51.0h， 生成 [4-[4-(Thiiran-2-ylmethylsulfonyl)phenoxy]phenyl] 2-aminoacetate;hydrochloride
  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

文献信息

• Structure–Activity Relationship for Thiirane-Based Gelatinase Inhibitors
  作者：Mijoon Lee、Masahiro Ikejiri、Dennis Klimpel、Marta Toth、Mana Espahbodi、Dusan Hesek、Christopher Forbes、Malika Kumarasiri、Bruce C. Noll、Mayland Chang、Shahriar Mobashery

  DOI：10.1021/ml300050b

  日期：2012.6.14

  inhibition. However, para- and some meta-substitutions of the terminal phenyl ring enhanced inhibitory activity and led to improve metabolic stability. This agrees with the result from metabolism studies with compound 1 that the primary route of biotransformation is oxidation, mainly at the para position of the phenyl ring and the α position of the sulfonyl group in the aliphatic side chain.

  本文报道了一项以 2-(4-苯氧基苯基磺酰基甲基) 硫杂环丙烷 ( 1 )为模板的广泛构效关系研究，该模板是一种有效且高度选择性的人明胶酶抑制剂。65 个新类似物的合成，每个都在多步过程中，允许探索分子模板的关键结构成分。该研究表明，磺酰甲基硫杂环丙烷和苯氧基苯基的存在对于明胶酶抑制很重要。然而，末端苯环的对位和一些间位取代增强了抑制活性并导致改善代谢稳定性。这与化合物1 的代谢研究结果一致生物转化的主要途径是氧化，主要在苯环的对位和脂肪族侧链中磺酰基的α位。
• Regioselective Control of the S_NAr Amination of 5-Substituted-2,4-Dichloropyrimidines Using Tertiary Amine Nucleophiles
  作者：Mijoon Lee、Tomas Rucil、Dusan Hesek、Allen G. Oliver、Jed F. Fisher、Shahriar Mobashery

  DOI：10.1021/acs.joc.5b01044

  日期：2015.8.7

  The SNAr reaction of 2,4-dichloropyrimidines, further substituted with an electron-withdrawing substituent at C-5, has selectivity for substitution at C-4. Here we report that tertiary amine nucleophiles show excellent C-2 selectivity. In situ N-dealkylation of an intermediate gives the product that formally corresponds to the reaction of a secondary amine nucleophile at C-2. This reaction is practical

  在C-5处进一步被吸电子取代基取代的2，4-二氯嘧啶的S N Ar反应具有在C-4处取代的选择性。在这里，我们报告叔胺亲核试剂显示出色的C-2选择性。中间体的原位N-去烷基化得到的产物形式上对应于仲胺亲核体在C-2处的反应。该反应是实用的（在简单的反应条件下快速，对叔胺结构具有良好的通用性，并且具有中等至优异的产率），并且显着扩大了嘧啶结构的获得。
• GELATINASE INHIBITORS AND PRODRUGS
  申请人：Chang Mayland

  公开号：US20130052184A1

  公开（公告）日：2013-02-28

  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.

  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。
• [EN] ACCELERATION OF DIABETIC WOUND HEALING<br/>[FR] ACCÉLÉRATION DE LA CICATRISATION DES PLAIES DIABÉTIQUES
  申请人：UNIV NOTRE DAME DU LAC

  公开号：WO2016044844A1

  公开（公告）日：2016-03-24

  The invention provides compounds, compositions, and methods to improve or accelerate the healing of a wound. In various embodiments, the methods can include the topical treatment of the wound with the enzyme MMP-8, or the topical treatment of the wound with MMP-8 in combination with administration of an MMP-9 inhibitor, to accelerate the healing of the wound.

  本发明提供了化合物、组成物和方法，以改善或加速伤口的愈合。在各种实施例中，该方法可以包括使用酶MMP-8局部治疗伤口，或者使用MMP-8与MMP-9抑制剂的联合局部治疗伤口，以加速伤口的愈合。
• Inhibitors of Matrix Metallaproteinases
  申请人：Lee Mijoon

  公开号：US20090005420A1

  公开（公告）日：2009-01-01

  The present invention provides novel compounds of formulas I-IX, as described herein. Also provided are compositions of compounds of formulas I-IX, methods of making compounds of formulas I-IX, and methods of using compounds of formulas I-IX. The compounds of the invention can be used to inhibit matrix metalloproteinases, and are useful to treat conditions and diseases associated therewith.

  本发明提供了式I-IX的新化合物，如本文所述。还提供了式I-IX化合物的组合物，制备式I-IX化合物的方法以及使用式I-IX化合物的方法。本发明中的化合物可用于抑制基质金属蛋白酶，并可用于治疗与之相关的疾病和症状。