N-methyl-N-(benzimidazol-2-yl)-N'-methyl-N'-t-butoxycarbonyl-1,3-propylenediamine | 215583-34-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: N-methyl-N-(benzimidazol-2-yl)-N'-methyl-N'-t-butoxycarbonyl-1,3-propylenediamine
• 英文别名: tert-butyl N-[3-[1H-benzimidazol-2-yl(methyl)amino]propyl]-N-methylcarbamate
• CAS: 215583-34-9
• 化学式: C₁₇H₂₆N₄O₂
• 分子量: 318.419
• InChiKey: GYTQHGHWJCGZJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  61.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-methyl-N-(benzimidazol-2-yl)-N'-methyl-N'-t-butoxycarbonyl-1,3-propylenediamine 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以87%的产率得到
  参考文献：
  名称：

  From Cells to Mice to Target: Characterization of NEU-1053 (SB-443342) and Its Analogues for Treatment of Human African Trypanosomiasis

  摘要：

  Human African trypanosomiasis is a neglected tropical disease that is lethal if left untreated. Existing therapeutics have limited efficacy and severe associated toxicities. 2-(2-(((3-((1H-Benzo[d]imidazol-2-yl)amino)propyl)amino)methyl)-4,6-dichloro-1H-indol-1-yl)ethan-1-ol (NEU-1053) has recently been identified from a high-throughput screen of >42,000 compounds as a highly potent and fast-acting trypanocidal agent capable of curing a bloodstream infection of Trypanosoma brucei in mice. We have designed a library of analogues to probe the structureactivity relationship and improve the predicted central nervous system (CNS) exposure of NEU-1053. We report the activity of these inhibitors of T. brucei, the efficacy of NEU-1053 in a murine CNS model of infection, and identification of the target of NEU-1053 via X-ray crystallography.

  DOI：

  10.1021/acsinfecdis.6b00202
• 作为产物：
  描述：

  2-羟基苯并咪唑 在 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 8.0h， 生成 N-methyl-N-(benzimidazol-2-yl)-N'-methyl-N'-t-butoxycarbonyl-1,3-propylenediamine
  参考文献：
  名称：

  From Cells to Mice to Target: Characterization of NEU-1053 (SB-443342) and Its Analogues for Treatment of Human African Trypanosomiasis

  摘要：

  Human African trypanosomiasis is a neglected tropical disease that is lethal if left untreated. Existing therapeutics have limited efficacy and severe associated toxicities. 2-(2-(((3-((1H-Benzo[d]imidazol-2-yl)amino)propyl)amino)methyl)-4,6-dichloro-1H-indol-1-yl)ethan-1-ol (NEU-1053) has recently been identified from a high-throughput screen of >42,000 compounds as a highly potent and fast-acting trypanocidal agent capable of curing a bloodstream infection of Trypanosoma brucei in mice. We have designed a library of analogues to probe the structureactivity relationship and improve the predicted central nervous system (CNS) exposure of NEU-1053. We report the activity of these inhibitors of T. brucei, the efficacy of NEU-1053 in a murine CNS model of infection, and identification of the target of NEU-1053 via X-ray crystallography.

  DOI：

  10.1021/acsinfecdis.6b00202

文献信息

• Benzimidazole compound
  申请人：Nissan Chemical Industries, Ltd.

  公开号：US06114369A1

  公开（公告）日：2000-09-05

  A benzimidazole derivative of the formula (I) or its salt: wherein A is a single bond or a C.sub.1-2 alkylene group (this alkylene group may optionally be substituted by a C.sub.1-4 alkyl group), R.sup.6 is a C.sub.1-4 alkyl group (this alkyl group may optionally be substituted by a phenyl group), B is a C.sub.2-3 alkylene group (this alkylene group may optionally be substituted by a C.sub.1-4 alkyl group), X is an oxygen atom, a sulfur atom or NR.sup.7 (wherein R.sup.7 is a nitro group, a cyano group or a C.sub.1-4 alkoxy group), each of R.sup.1 and R.sup.2 which are independent of each other, is a hydrogen atom, a halogen atom, a C.sub.1-4 alkyl group or a C.sub.1-4 alkoxy group, E is a C.sub.1-2 alkylene group (this alkylene group may optionally be substituted by a C.sub.1-4 alkyl group), R.sup.3 is a phenyl group (this phenyl group may optionally be substituted by a halogen atom, a C.sub.1-4 alkyl group or a C.sub.1-4 alkoxy group), a C.sub.1-4 alkoxy group or a benzyloxy group, each of R.sup.4 and R.sup.5 which are independent of each other, is a C.sub.1-4 alkyl group (this alkyl group may optionally be substituted by a phenyl group), D is a C.sub.1-2 alkylene group (this alkylene group may optionally be substituted by a C.sub.1-4 alkyl group), and Ar is a phenyl group.

  公式（I）或其盐的苯并咪唑衍生物：其中A为单键或C.sub.1-2烷基（该烷基可选择性地被C.sub.1-4烷基取代），R.sup.6为C.sub.1-4烷基（该烷基可选择性地被苯基取代），B为C.sub.2-3烷基（该烷基可选择性地被C.sub.1-4烷基取代），X为氧原子、硫原子或NR.sup.7（其中R.sup.7为硝基、氰基或C.sub.1-4烷氧基），R.sup.1和R.sup.2各自独立地为氢原子、卤素原子、C.sub.1-4烷基或C.sub.1-4烷氧基，E为C.sub.1-2烷基（该烷基可选择性地被C.sub.1-4烷基取代），R.sup.3为苯基（该苯基可选择性地被卤素原子、C.sub.1-4烷基或C.sub.1-4烷氧基取代）、C.sub.1-4烷氧基或苄氧基，R.sup.4和R.sup.5各自独立地为C.sub.1-4烷基（该烷基可选择性地被苯基取代），D为C.sub.1-2烷基（该烷基可选择性地被C.sub.1-4烷基取代），Ar为苯基。
• BENZIMIDAZOLE DERIVATIVE
  申请人：Nissan Chemical Industries, Ltd.

  公开号：EP0980359B1

  公开（公告）日：2004-06-23
• US6114369A
  申请人：——

  公开号：US6114369A

  公开（公告）日：2000-09-05
• From Cells to Mice to Target: Characterization of NEU-1053 (SB-443342) and Its Analogues for Treatment of Human African Trypanosomiasis
  作者：William G. Devine、Rosario Diaz-Gonzalez、Gloria Ceballos-Perez、Domingo Rojas、Takashi Satoh、Westley Tear、Ranae M. Ranade、Ximena Barros-Álvarez、Wim G. J. Hol、Frederick S. Buckner、Miguel Navarro、Michael P. Pollastri

  DOI：10.1021/acsinfecdis.6b00202

  日期：2017.3.10

  Human African trypanosomiasis is a neglected tropical disease that is lethal if left untreated. Existing therapeutics have limited efficacy and severe associated toxicities. 2-(2-(((3-((1H-Benzo[d]imidazol-2-yl)amino)propyl)amino)methyl)-4,6-dichloro-1H-indol-1-yl)ethan-1-ol (NEU-1053) has recently been identified from a high-throughput screen of >42,000 compounds as a highly potent and fast-acting trypanocidal agent capable of curing a bloodstream infection of Trypanosoma brucei in mice. We have designed a library of analogues to probe the structureactivity relationship and improve the predicted central nervous system (CNS) exposure of NEU-1053. We report the activity of these inhibitors of T. brucei, the efficacy of NEU-1053 in a murine CNS model of infection, and identification of the target of NEU-1053 via X-ray crystallography.