N-(2-hydroxybenzyl)-2-hydroxy-5-methylphenylamine | 1361309-62-7

• 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: N-(2-hydroxybenzyl)-2-hydroxy-5-methylphenylamine
• 英文别名: 2-[(2-hydroxyphenyl)methylamino]-4-methylphenol
• CAS: 1361309-62-7
• 化学式: C₁₄H₁₅NO₂
• 分子量: 229.279
• InChiKey: AIAVGLNTWICCBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.02
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  52.49
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  二硫化碳 、 N-(2-hydroxybenzyl)-2-hydroxy-5-methylphenylamine 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 16.0h， 以0.87 g的产率得到N-(2-hydroxybenzyl)-5-methylbenzoxazol-2-thione
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of New N-(Phenylmethyl)-benzoxazol-2-thiones as Macrophage Migration Inhibitory Factor (MIF) Antagonists: Efficacies in Experimental Pulmonary Hypertension

  摘要：

  Macrophage migration inhibitory factor (MIF) is a key pleiotropic mediator and a promising therapeutic target in cancer as well as in several inflammatory and cardiovascular diseases including pulmonary arterial hypertension (PAH). Here, a novel series of N-(phenylmethyl)-benzoxazol-2-thiones 5-32 designed to target the MIF tautomerase active site was synthesized and evaluated for its effects on cell survival. Investigation of structure-activity relationship (SAR) particularly at the 5-position of the benzoxazole core led to the identification of 31 that potently inhibits cell survival in DU-145 prostate cancer cells and pulmonary endothelial cells derived from patients with idiopathic PAH (iPAH-ECs), two cell lines for which survival is MIF-dependent. Molecular docking studies helped to interpret initial SAR related to MIF tautomerase inhibition and propose preferred binding mode for 31 within the MIF tautomerase active site. Interestingly, daily treatment with 31 started 2 weeks after a subcutaneous monocrotaline injection regressed established pulmonary hypertension in rats.

  DOI：

  10.1021/acs.jmedchem.7b01312
• 作为产物：
  描述：

  水杨醛 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 N-(2-hydroxybenzyl)-2-hydroxy-5-methylphenylamine
  参考文献：
  名称：

  不对称N封端的三脚架NO 3配体与铁（III），氧钒（V）和二氧钼（VI）金属中心的配位化学

  摘要：

  铁（III）[Fe（L 1）] 2（1），氧钒（V）[VO（L 1）]（2）和二氧钼（VI）K [MoO 2（L ）的合成和表征1）]（3）报道了由部分不对称的N-封端的三脚架NO 3配体（L 1）支撑的络合物。配合物1和2是通过配体[H 3 L 1 ]与它们相应的金属前体（FeCl 3和VOCl 3分别在三乙胺的THF中存在，而3则通过在甲醇中用相同的配体和氢氧化钾处理[MoO 2（acac）2 ]（acac =乙酰丙酮酸酯）以类似的方式获得。的X射线晶体结构1示出了具有一个二聚结构的双- （μ -phenoxo）的Fe 2 ö 2金刚石核心，并且每个铁中心带有一个罕见NO 4配位球。先前未知的，完全不对称的N封端的三脚架NO 3配体[H 3 L 2还描述了以三个不同的酚类臂为特征的化合物。[H 3 L 2 ]与VOCl 3的反应产生了氧-钒（V）络合物[VO（L 2）]（4）。配合物2

  DOI：

  10.1016/j.ica.2011.10.054

文献信息

• The coordination chemistry of unsymmetric N-capped tripodal NO3 ligands with iron(III), oxo-vanadium(V) and dioxo-molybdenum(VI) metal centres
  作者：Lok H. Tong、Yee-Lok Wong、Hung Kay Lee、Jonathan R. Dilworth

  DOI：10.1016/j.ica.2011.10.054

  日期：2012.3

  in THF, while 3 was obtained in a similar manner by treating [MoO2(acac)2] (acac = acetylacetonate) with the same proligand and potassium hydroxide in methanol. The X-ray crystal structure of 1 illustrates a dimeric structure with a bis-(μ-phenoxo) Fe2O2 diamond core, and each iron centre bears a rare NO4 coordination sphere. The preparation of a previously unknown, fully unsymmetric N-capped tripodal

  铁（III）[Fe（L 1）] 2（1），氧钒（V）[VO（L 1）]（2）和二氧钼（VI）K [MoO 2（L ）的合成和表征1）]（3）报道了由部分不对称的N-封端的三脚架NO 3配体（L 1）支撑的络合物。配合物1和2是通过配体[H 3 L 1 ]与它们相应的金属前体（FeCl 3和VOCl 3分别在三乙胺的THF中存在，而3则通过在甲醇中用相同的配体和氢氧化钾处理[MoO 2（acac）2 ]（acac =乙酰丙酮酸酯）以类似的方式获得。的X射线晶体结构1示出了具有一个二聚结构的双- （μ -phenoxo）的Fe 2 ö 2金刚石核心，并且每个铁中心带有一个罕见NO 4配位球。先前未知的，完全不对称的N封端的三脚架NO 3配体[H 3 L 2还描述了以三个不同的酚类臂为特征的化合物。[H 3 L 2 ]与VOCl 3的反应产生了氧-钒（V）络合物[VO（L 2）]（4）。配合物2
• Design, Synthesis, and Biological Activity of New <i>N</i>-(Phenylmethyl)-benzoxazol-2-thiones as Macrophage Migration Inhibitory Factor (MIF) Antagonists: Efficacies in Experimental Pulmonary Hypertension
  作者：Morane Le Hiress、Bernardin Akagah、Guillaume Bernadat、Ly Tu、Raphaël Thuillet、Alice Huertas、Carole Phan、Elie Fadel、Gérald Simonneau、Marc Humbert、Gaël Jalce、Christophe Guignabert

  DOI：10.1021/acs.jmedchem.7b01312

  日期：2018.4.12

  Macrophage migration inhibitory factor (MIF) is a key pleiotropic mediator and a promising therapeutic target in cancer as well as in several inflammatory and cardiovascular diseases including pulmonary arterial hypertension (PAH). Here, a novel series of N-(phenylmethyl)-benzoxazol-2-thiones 5-32 designed to target the MIF tautomerase active site was synthesized and evaluated for its effects on cell survival. Investigation of structure-activity relationship (SAR) particularly at the 5-position of the benzoxazole core led to the identification of 31 that potently inhibits cell survival in DU-145 prostate cancer cells and pulmonary endothelial cells derived from patients with idiopathic PAH (iPAH-ECs), two cell lines for which survival is MIF-dependent. Molecular docking studies helped to interpret initial SAR related to MIF tautomerase inhibition and propose preferred binding mode for 31 within the MIF tautomerase active site. Interestingly, daily treatment with 31 started 2 weeks after a subcutaneous monocrotaline injection regressed established pulmonary hypertension in rats.