tert-butyl 3-(3-(thiophen-3-yl)ureido)propylcarbamate | 1386975-96-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: tert-butyl 3-(3-(thiophen-3-yl)ureido)propylcarbamate
• CAS: 1386975-96-7
• 化学式: C₁₃H₂₁N₃O₃S
• 分子量: 299.394
• InChiKey: MCFYUJACSLQUDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.78
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  79.46
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(3-(thiophen-3-yl)ureido)propylcarbamate 在 三异丙基硅基三氟甲磺酸酯 、 sodium methylate 、 三氟乙酸 作用下， 以 甲醇 、 水 为溶剂， 反应 1.75h， 生成 1-[3-(3-chloro-5-methoxy-benzylamino)propyl]-3-(thiophen-3-yl)urea
  参考文献：
  名称：

  Urea-Based Inhibitors of Trypanosoma brucei Methionyl-tRNA Synthetase: Selectivity and in Vivo Characterization

  摘要：

  Urea-based methionyl-tRNA synthetase inhibitors were designed, synthesized, and evaluated for their potential toward treating human African trypanosomiasis (HAT). With the aid of a homology model and a structure activity-relationship approach, low nM inhibitors were discovered that show high selectivity toward the parasite enzyme over the closest human homologue. These compounds inhibit parasite growth with EC50 values as low as 0.15 mu M while having low toxicity to mammalian cells. Two compounds (2 and 26) showed excellent membrane permeation in the MDR1-MDCKII model and encouraging oral pharmacokinetic properties in mice. Compound 2 was confirmed to enter the CNS in mice. Compound 26 had modest suppressive activity against Trpanosoma brucei rhodesiense in the mouse model, suggesting that more potent analogues or compounds with higher exposures need to be developed. The urea-based inhibitors are thus a promising starting point for further optimization toward the discovery of orally available and CNS active drugs to treat HAT.

  DOI：

  10.1021/jm300303e
• 作为产物：
  描述：

  N-叔丁氧羰基-1,3-丙二胺 、 3-噻吩异氰酸酯 以 二氯甲烷 为溶剂， 生成 tert-butyl 3-(3-(thiophen-3-yl)ureido)propylcarbamate
  参考文献：
  名称：

  Urea-Based Inhibitors of Trypanosoma brucei Methionyl-tRNA Synthetase: Selectivity and in Vivo Characterization

  摘要：

  Urea-based methionyl-tRNA synthetase inhibitors were designed, synthesized, and evaluated for their potential toward treating human African trypanosomiasis (HAT). With the aid of a homology model and a structure activity-relationship approach, low nM inhibitors were discovered that show high selectivity toward the parasite enzyme over the closest human homologue. These compounds inhibit parasite growth with EC50 values as low as 0.15 mu M while having low toxicity to mammalian cells. Two compounds (2 and 26) showed excellent membrane permeation in the MDR1-MDCKII model and encouraging oral pharmacokinetic properties in mice. Compound 2 was confirmed to enter the CNS in mice. Compound 26 had modest suppressive activity against Trpanosoma brucei rhodesiense in the mouse model, suggesting that more potent analogues or compounds with higher exposures need to be developed. The urea-based inhibitors are thus a promising starting point for further optimization toward the discovery of orally available and CNS active drugs to treat HAT.

  DOI：

  10.1021/jm300303e