N-Benzyl-N'-(carboxymethyl)thiourea | 134124-35-9

• 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-Benzyl-N'-(carboxymethyl)thiourea
• 英文别名: 5-benzyl-4-thio-hydantoic acid；N-Benzylthiocarbamoyl-glycin；5-Benzyl-4-thio-hydantoinsaeure；2-(Benzylcarbamothioylamino)acetic acid
• CAS: 134124-35-9
• 化学式: C₁₀H₁₂N₂O₂S
• 分子量: 224.283
• InChiKey: DBHKEXXUZOITLN-UHFFFAOYSA-N

物化性质

• 沸点：
  408.0±55.0 °C(Predicted)
• 密度：
  1.300±0.06 g/cm3(Predicted)
• 溶解度：
  >33.6 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  93.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-Benzyl-N'-(carboxymethyl)thiourea 在 硫酸 作用下， 以 丙酮 为溶剂， 以8.86 g的产率得到3-苄基-2-巯基-3,5-二氢-4H-咪唑-4-酮
  参考文献：
  名称：

  氨基酸轻松转化为 1-烷基咪唑-2-硫酮，以及用过氧化苯甲酰将其氧化脱硫为咪唑

  摘要：

  甘氨酸用异硫氰酸酯酰化并缩合为 3-烷基 2-硫代乙内酰脲，再用硼氢化钠和氯化锂的混合物还原并脱水为 1-烷基咪唑-2-硫酮。用过氧化苯甲酰将它们氧化脱硫成咪唑。模型化合物不需要色谱。开发的方法用于将酪氨酸精制为 1,4-二（对甲氧基苄基）咪唑，这是从海绵 Leucetta 合成三种咪唑的常见中间体。

  DOI：

  10.1055/s-2007-983740
• 作为产物：
  描述：

  异硫氰酸苯甲酯 、 聚甘氨酸 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 N-Benzyl-N'-(carboxymethyl)thiourea
  参考文献：
  名称：

  氨基酸轻松转化为 1-烷基咪唑-2-硫酮，以及用过氧化苯甲酰将其氧化脱硫为咪唑

  摘要：

  甘氨酸用异硫氰酸酯酰化并缩合为 3-烷基 2-硫代乙内酰脲，再用硼氢化钠和氯化锂的混合物还原并脱水为 1-烷基咪唑-2-硫酮。用过氧化苯甲酰将它们氧化脱硫成咪唑。模型化合物不需要色谱。开发的方法用于将酪氨酸精制为 1,4-二（对甲氧基苄基）咪唑，这是从海绵 Leucetta 合成三种咪唑的常见中间体。

  DOI：

  10.1055/s-2007-983740

文献信息

• Facile Conversion of Amino Acids into 1-Alkyl Imidazole-2-thiones, and Their Oxidative Desulfurization to Imidazoles with Benzoyl Peroxide
  作者：Peter Schreiner、Derek Wolfe

  DOI：10.1055/s-2007-983740

  日期：2007.7

  condensed to 3-alkyl 2-thiohydantoins, which were reduced with a mixture of sodium borohydride and lithium chloride and dehydrated to 1-alkyl imidazole-2-thiones. These were oxidatively desulfurized to imidazoles with benzoyl peroxide. No chromatography was required for model compounds. The methods developed were used to elaborate tyrosine to 1,4 -di(p -methoxybenzyl)imidazole, a common intermediate in

  甘氨酸用异硫氰酸酯酰化并缩合为 3-烷基 2-硫代乙内酰脲，再用硼氢化钠和氯化锂的混合物还原并脱水为 1-烷基咪唑-2-硫酮。用过氧化苯甲酰将它们氧化脱硫成咪唑。模型化合物不需要色谱。开发的方法用于将酪氨酸精制为 1,4-二（对甲氧基苄基）咪唑，这是从海绵 Leucetta 合成三种咪唑的常见中间体。
• Madan; Taneja, Journal of the Indian Chemical Society, 1991, vol. 68, # 3, p. 162 - 163
  作者：Madan、Taneja

  DOI：——

  日期：——
• The cyclization of substituted N-thiocarbamoylglycines, and some merocyanine dyes derived from the products
  作者：R. A. Jeffreys

  DOI：10.1039/jr9540002221

  日期：——
• Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds
  作者：Fangrui Wu、Hong Jiang、Baisong Zheng、Mari Kogiso、Yuan Yao、Chao Zhou、Xiao-Nan Li、Yongcheng Song

  DOI：10.1021/acs.jmedchem.5b00684

  日期：2015.9.10

  Somatic mutations of isocitrate dehydrogenase 1 (LDH1) at R132 are frequently found in certain cancers such as glioma. With losing the activity of wild-type IDH1, the R132H and R132C mutant proteins can reduce alpha-ketoglutaric acid (alpha-KG) to D-2-hydroxyglutaric acid (D2HG). The resulting high concentration of D2HG inhibits many alpha-KG-dependent dioxygenases, including histone demethylases, to cause broad histone hypermethylation. These aberrant epigenetic changes are responsible for the initiation of these cancers. We report the synthesis, structure activity relationships, enzyme kinetics, and binding thermodynamics of a novel series of 2-thiohydantoin and related compounds, among which several compounds are potent inhibitors of mutant IDH1 with K-i as low as 420 nM. X-ray crystal structures of IDH1(R132H) in complex with two inhibitors are reported, showing their inhibitor-protein interactions. These compounds can decrease the cellular concentration of D2HG, reduce the levels of histone methylation, and suppress the proliferation of stem-like cancer cells in BT142 glioma with IDH1 R132H mutation.