2-(2-(methoxyamino)ethyl)isoindoline-1,3-dione | 1048037-09-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(2-(methoxyamino)ethyl)isoindoline-1,3-dione
• 英文别名: 2-[2-(Methoxyamino)ethyl]isoindole-1,3-dione；2-[2-(methoxyamino)ethyl]isoindole-1,3-dione
• CAS: 1048037-09-7
• 化学式: C₁₁H₁₂N₂O₃
• mdl: MFCD25954865
• 分子量: 220.228
• InChiKey: KWCDRZWTHPLYJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2-(methoxyamino)ethyl)isoindoline-1,3-dione 、 bis(4-isothiocyanatophenyl)amine 以 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 以83%的产率得到1,1'-(4,4'-azanediylbis(4,1-phenylene)bis(3-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-3-methoxy))thiourea
  参考文献：
  名称：

  Synthesis and Antiprotozoal Activity of N-Alkoxy Analogues of the Trypanocidal Lead Compound 4,4′-Bis(imidazolinylamino)diphenylamine with Improved Human Blood−Brain Barrier Permeability

  摘要：

  To improve the blood brain barrier permeability of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine (1), five N-alkoxy analogues were synthesized from bis(4-isothiocyanatophenyl)amine and N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides following successive chemical reactions in just one reactor ("one-pot procedure"). This involved: (a) formation of a thiourea intermediate, (b) removal of the amine protecting groups, and (c) intramolecular cyclization. The blood brain barrier permeability of the compounds determined in vitro by transport assays through the hCMEC/D3 human cell line, a well-known and characterized human cellular blood brain barrier model, showed that the N-hydroxy analogue 16 had enhanced blood brain barrier permeability compared with the unsubstituted lead compound. Moreover, this compound displayed low micromolar IC50 against Trypanosoma brucei rhodesiense and Plasmodium falciparum and moderate activity by intraperitoneal administration in the STIB900 m urine model of acute sleeping sickness.

  DOI：

  10.1021/jm101335q
• 作为产物：
  描述：

  3-氯苯甲酰乙腈 、 N-(2-溴乙基)邻苯二甲酰亚胺 以 乙腈 为溶剂， 反应 43.0h， 以80 mg的产率得到2-(2-(methoxyamino)ethyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Synthesis and Antiprotozoal Activity of N-Alkoxy Analogues of the Trypanocidal Lead Compound 4,4′-Bis(imidazolinylamino)diphenylamine with Improved Human Blood−Brain Barrier Permeability

  摘要：

  To improve the blood brain barrier permeability of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine (1), five N-alkoxy analogues were synthesized from bis(4-isothiocyanatophenyl)amine and N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides following successive chemical reactions in just one reactor ("one-pot procedure"). This involved: (a) formation of a thiourea intermediate, (b) removal of the amine protecting groups, and (c) intramolecular cyclization. The blood brain barrier permeability of the compounds determined in vitro by transport assays through the hCMEC/D3 human cell line, a well-known and characterized human cellular blood brain barrier model, showed that the N-hydroxy analogue 16 had enhanced blood brain barrier permeability compared with the unsubstituted lead compound. Moreover, this compound displayed low micromolar IC50 against Trypanosoma brucei rhodesiense and Plasmodium falciparum and moderate activity by intraperitoneal administration in the STIB900 m urine model of acute sleeping sickness.

  DOI：

  10.1021/jm101335q

文献信息

• Synthesis and Antiprotozoal Activity of <i>N</i>-Alkoxy Analogues of the Trypanocidal Lead Compound 4,4′-Bis(imidazolinylamino)diphenylamine with Improved Human Blood−Brain Barrier Permeability
  作者：Lidia Nieto、Ainhoa Mascaraque、Florence Miller、Fabienne Glacial、Carlos Ríos Martínez、Marcel Kaiser、Reto Brun、Christophe Dardonville

  DOI：10.1021/jm101335q

  日期：2011.1.27

  To improve the blood brain barrier permeability of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine (1), five N-alkoxy analogues were synthesized from bis(4-isothiocyanatophenyl)amine and N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides following successive chemical reactions in just one reactor ("one-pot procedure"). This involved: (a) formation of a thiourea intermediate, (b) removal of the amine protecting groups, and (c) intramolecular cyclization. The blood brain barrier permeability of the compounds determined in vitro by transport assays through the hCMEC/D3 human cell line, a well-known and characterized human cellular blood brain barrier model, showed that the N-hydroxy analogue 16 had enhanced blood brain barrier permeability compared with the unsubstituted lead compound. Moreover, this compound displayed low micromolar IC50 against Trypanosoma brucei rhodesiense and Plasmodium falciparum and moderate activity by intraperitoneal administration in the STIB900 m urine model of acute sleeping sickness.