1-Amino-3-(2-piperazin-1-ylethyl)thiourea | 688789-78-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-Amino-3-(2-piperazin-1-ylethyl)thiourea
• CAS: 688789-78-8
• 化学式: C₇H₁₇N₅S
• 分子量: 203.311
• InChiKey: BEXGYBDBOBVKEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  97.4
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-溴苯丙酮 、 1-Amino-3-(2-piperazin-1-ylethyl)thiourea 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 (1E)-1-(3-bromophenyl)propan-1-one N-(2-piperazin-1-ylethyl)thiosemicarbazone
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Study of Potent Trypanocidal Thio Semicarbazone Inhibitors of the Trypanosomal Cysteine Protease Cruzain

  摘要：

  American trypanosomiasis, or Chagas' disease, is the leading cause of heart disease in Latin America. Currently there is an urgent need to develop antitrypanosomal therapy due to the toxicity of existing agents and emerging drug resistance. A novel series of potent thio semicarbazone small-molecule inhibitors of the Trypanosoma cruzi cysteine protease cruzain have been identified. Some of these inhibitors have been shown to be trypanocidal. We initially discovered that X-bromopropiophenone thio semicarbazone (1i) inhibited cruzain and could cure mammalian cell cultures infected with T cruzi. 3'-Bromopropiophenone thio semicarbazone showed no toxicity for mammalian cells at concentrations that were trypanocidal. Following this lead, more than 100 compounds were designed and synthesized. A specific structure-activity relationship (SAR) was established, and many potent analogues with IC50 values in the low nanomolar range were identified. Eight additional analogues were trypanocidal in a cell culture assay, and this indicates that aryl thio semicarbazone is a productive scaffold for killing the parasites. Kinetic studies show that these are time-dependent inhibitors. Molecular modeling studies of the enzyme-inhibitor complex have led to a proposed mechanism of interaction as well as insight into the SAR of the thio semicarbazone series. The nonpeptide nature of this series, small size, and extremely low cost of production suggest this is a promising direction for the development of new antitrypanosome chemotherapy.

  DOI：

  10.1021/jm010459j
• 作为产物：
  描述：

  1-(2-异硫氰酸基乙基)哌嗪 在 肼 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以80%的产率得到1-Amino-3-(2-piperazin-1-ylethyl)thiourea
  参考文献：
  名称：

  Synthesis of new alkylaminoalkyl thiosemicarbazones of 3-acetylindole and their effect on DNA synthesis and cell proliferation

  摘要：

  The preparation of a number of thiosemicarbazones of 3-acetylindole is described. These compounds were evaluated in vitro for their effect on proliferation and cell-division delays in cultured human peripheral blood lymphocytes, and their effect on DNA synthesis in T-cell leukemia Molt-4 cells.

  DOI：

  10.1016/0223-5234(96)88215-8

文献信息

• Synthesis and Structure−Activity Relationship Study of Potent Trypanocidal Thio Semicarbazone Inhibitors of the Trypanosomal Cysteine Protease Cruzain
  作者：Xiaohui Du、Chun Guo、Elizabeth Hansell、Patricia S. Doyle、Conor R. Caffrey、Tod P. Holler、James H. McKerrow、Fred E. Cohen

  DOI：10.1021/jm010459j

  日期：2002.6.1

  American trypanosomiasis, or Chagas' disease, is the leading cause of heart disease in Latin America. Currently there is an urgent need to develop antitrypanosomal therapy due to the toxicity of existing agents and emerging drug resistance. A novel series of potent thio semicarbazone small-molecule inhibitors of the Trypanosoma cruzi cysteine protease cruzain have been identified. Some of these inhibitors have been shown to be trypanocidal. We initially discovered that X-bromopropiophenone thio semicarbazone (1i) inhibited cruzain and could cure mammalian cell cultures infected with T cruzi. 3'-Bromopropiophenone thio semicarbazone showed no toxicity for mammalian cells at concentrations that were trypanocidal. Following this lead, more than 100 compounds were designed and synthesized. A specific structure-activity relationship (SAR) was established, and many potent analogues with IC50 values in the low nanomolar range were identified. Eight additional analogues were trypanocidal in a cell culture assay, and this indicates that aryl thio semicarbazone is a productive scaffold for killing the parasites. Kinetic studies show that these are time-dependent inhibitors. Molecular modeling studies of the enzyme-inhibitor complex have led to a proposed mechanism of interaction as well as insight into the SAR of the thio semicarbazone series. The nonpeptide nature of this series, small size, and extremely low cost of production suggest this is a promising direction for the development of new antitrypanosome chemotherapy.
• Synthesis of new alkylaminoalkyl thiosemicarbazones of 3-acetylindole and their effect on DNA synthesis and cell proliferation
  作者：T Siatra-Papastaikoudi、A Tsotinis、CP Raptopoulou、C Sambani、H Thomou

  DOI：10.1016/0223-5234(96)88215-8

  日期：1995.1

  The preparation of a number of thiosemicarbazones of 3-acetylindole is described. These compounds were evaluated in vitro for their effect on proliferation and cell-division delays in cultured human peripheral blood lymphocytes, and their effect on DNA synthesis in T-cell leukemia Molt-4 cells.