tert-butyl (3-(3-phenylureido)propyl)carbamate | 1386975-95-6

• 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: tert-butyl (3-(3-phenylureido)propyl)carbamate
• 英文别名: tert-butyl N-[3-(phenylcarbamoylamino)propyl]carbamate
• CAS: 1386975-95-6
• 化学式: C₁₅H₂₃N₃O₃
• 分子量: 293.366
• InChiKey: FPUAYEOMQHSMMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  79.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (3-(3-phenylureido)propyl)carbamate 在 sodium methylate 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.75h， 生成 1-[3-[(3-Ethoxyphenyl)methylamino]propyl]-3-phenylurea
  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 、 异氰酸苯酯 以 二氯甲烷 为溶剂， 以100%的产率得到tert-butyl (3-(3-phenylureido)propyl)carbamate
  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

文献信息

• [EN] SPECIFIC SMALL MOLECULE INHIBITORS THAT BLOCK KMT9 METHYLTRANSFERASE ACTIVITY AND FUNCTION<br/>[FR] INHIBITEURS À PETITES MOLÉCULES SPÉCIFIQUES QUI BLOQUENT L'ACTIVITÉ ET LA FONCTION DE LA MÉTHYLTRANSFÉRASE KMT9
  申请人：[en]ALBERT-LUDWIGS-UNIVERSITÄT FREIBURG

  公开号：WO2023017152A1

  公开（公告）日：2023-02-16

  The present invention relates to novel specific small molecule inhibitors that block KMT9 methyltransferase activity. In particular, the present invention is concerned with a compound of formula (I) wherein X1, X2, X3, X4, R1, R2, R3, R5, R6and L are as defined herein. Further, the present invention is concerned with a pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula (I). The present invention also relates to a compound of formula (I) and a pharmaceutical composition comprising a compound of formula (I) for use in medicine. Yet further, the present invention is concerned with a compound of formula (I) and a pharmaceutical composition comprising a compound of formula (I) for use as inhibitor of KMT9. Finally, the present invention is concerned with a compound of formula (I), wherein X1, X2, X3, X4, R1, R2, R3, R5, R6and L are as defined herein, for use in the treatment of cancer selected from the group as defined herein.