N-(乙基硫代氨基甲酰)甘氨酸 | 134124-34-8

• 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
• 中文名称: N-(乙基硫代氨基甲酰)甘氨酸
• 英文名称: N-Ethyl-N'-(carboxymethyl)thiourea
• 英文别名: 5-ethyl-4-thio-hydantoic acid；N-Aethylthiocarbamoyl-glycin；5-Aethyl-4-thio-hydantoinsaeure；Glycine, N-[(ethylamino)thioxomethyl]-(9CI)；2-(ethylcarbamothioylamino)acetic acid
• CAS: 134124-34-8
• 化学式: C₅H₁₀N₂O₂S
• 分子量: 162.213
• InChiKey: NDFJHOSKGQKOIN-UHFFFAOYSA-N

物化性质

• 熔点：
  170 °C (decomp)
• 沸点：
  293.6±42.0 °C(Predicted)
• 密度：
  1.264±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  93.4
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 储存条件：
  室温下保存，并避免光照。

反应信息

• 作为反应物：
  描述：

  N-(乙基硫代氨基甲酰)甘氨酸 在 硫酸 作用下， 以 丙酮 为溶剂， 生成 3-乙基-2-硫代乙内酰脲
  参考文献：
  名称：

  Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b00684
• 作为产物：
  描述：

  异硫氰酸乙酯 、 聚甘氨酸 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 48.0h， 生成 N-(乙基硫代氨基甲酰)甘氨酸
  参考文献：
  名称：

  Madan; Taneja, Journal of the Indian Chemical Society, 1991, vol. 68, # 3, p. 162 - 163

  摘要：

  DOI：

文献信息

• 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：——
• Madan; Taneja, Journal of the Indian Chemical Society, 1991, vol. 68, # 3, p. 162 - 163
  作者：Madan、Taneja

  DOI：——

  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.