4-(2-isothiocyanato-1-methylethyl)phenol

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-(2-isothiocyanato-1-methylethyl)phenol
• 英文别名: 2-(4-hydroxy-phenyl)-propyl isothiocyanate；2-(4-Hydroxy-phenyl)-propylisothiocyanat；4-(β-Isothiocyanato-isopropyl)-phenol；4-(1-Isothiocyanatopropan-2-yl)phenol
• 化学式: C₁₀H₁₁NOS
• 分子量: 193.269
• InChiKey: WTDFRIJJYCZRLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  64.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 三苯基膦氢溴酸盐 作用下， 以 乙腈 为溶剂， 生成 4-(2-isothiocyanato-1-methylethyl)phenol
  参考文献：
  名称：

  Multiple binding modes of isothiocyanates that inhibit macrophage migration inhibitory factor

  摘要：

  Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has roles in the innate immune response, and also contributes to inflammatory disease. While the biological properties of MIF are closely linked to protein protein interactions, MW also has tautomerase activity. Inhibition of this activity interferes with the interaction of MIF with protein partners e.g. the CD74 receptor, and tautomerase inhibitors show promise in disease models including multiple sclerosis and colitis. Isothiocyanates inhibit MIF tautomerase activity via covalent modification of the N-terminal proline. We systematically explored variants of benzyl and phenethyl isothiocyanates, to define determinants of inhibition. In particular, substitution with hydroxyl, chloro, fluoro and trifluoro moieties at the para and meta positions were evaluated. In assays on treated cells and recombinant protein, the IC50 varied from 250 nM to >100 mu M. X-ray crystal structures of selected complexes revealed that two binding modes are accessed by some compounds, perhaps owing to strain in short linkers between the isothiocyanate and aromatic ring. The variety of binding modes confirms the existence of two subsites for inhibitors and establishes a platform for the development of potent inhibitors of MIF that only need to target one of these subsites. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.02.012

文献信息

• Thiazolinephenols. 5-Methyl- and 5,5-Dimethylthiazolinephenols, By-Products and Derivatives
  作者：William F. Hart、Joseph B. Niederl

  DOI：10.1021/ja01874a041

  日期：1939.5
• Multiple binding modes of isothiocyanates that inhibit macrophage migration inhibitory factor
  作者：Emma S. Spencer、Edward J. Dale、Aimée L. Gommans、Malcolm T. Rutledge、Christine T. Vo、Yoshio Nakatani、Allan B. Gamble、Robin A.J. Smith、Sigurd M. Wilbanks、Mark B. Hampton、Joel D.A. Tyndall

  DOI：10.1016/j.ejmech.2015.02.012

  日期：2015.3

  Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has roles in the innate immune response, and also contributes to inflammatory disease. While the biological properties of MIF are closely linked to protein protein interactions, MW also has tautomerase activity. Inhibition of this activity interferes with the interaction of MIF with protein partners e.g. the CD74 receptor, and tautomerase inhibitors show promise in disease models including multiple sclerosis and colitis. Isothiocyanates inhibit MIF tautomerase activity via covalent modification of the N-terminal proline. We systematically explored variants of benzyl and phenethyl isothiocyanates, to define determinants of inhibition. In particular, substitution with hydroxyl, chloro, fluoro and trifluoro moieties at the para and meta positions were evaluated. In assays on treated cells and recombinant protein, the IC50 varied from 250 nM to >100 mu M. X-ray crystal structures of selected complexes revealed that two binding modes are accessed by some compounds, perhaps owing to strain in short linkers between the isothiocyanate and aromatic ring. The variety of binding modes confirms the existence of two subsites for inhibitors and establishes a platform for the development of potent inhibitors of MIF that only need to target one of these subsites. (C) 2015 Elsevier Masson SAS. All rights reserved.