3-(3-Chlorophenyl)-4-methyl-2-pyrazoline-1-thiocarboxamide | 443144-68-1

• 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: 3-(3-Chlorophenyl)-4-methyl-2-pyrazoline-1-thiocarboxamide
• 英文别名: 3-(3-Chloro-phenyl)-4-methyl-4,5-dihydro-pyrazole-1-carbothioic acid amide；5-(3-chlorophenyl)-4-methyl-3,4-dihydropyrazole-2-carbothioamide
• CAS: 443144-68-1
• 化学式: C₁₁H₁₂ClN₃S
• 分子量: 253.755
• InChiKey: KUETXCHGKVOJOE-UHFFFAOYSA-N

物化性质

• 熔点：
  131.3 °C (decomp)
• 沸点：
  386.7±44.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  73.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,3-二氯喹喔啉 、 3-(3-Chlorophenyl)-4-methyl-2-pyrazoline-1-thiocarboxamide 以 乙醇 为溶剂， 以41%的产率得到2-[5-(3-Chlorophenyl)-4-methyl-3,4-dihydropyrazol-2-yl]-[1,3]thiazolo[4,5-b]quinoxaline
  参考文献：
  名称：

  Synthesis, characterization and antiamoebic activity of 1-(thiazolo[4,5-b]quinoxaline-2-yl)-3-phenyl-2-pyrazoline derivatives

  摘要：

  A new series of 1-N-thiocarboxamide-3-phenyl-2-pyrazolines 1-6 was synthesized by cyclization of different Mannich bases with unsubstituted thiosemicarbazide. The reaction of cyclized pyrazoline derivatives 1-6 with 2,3-dichloroquinoxaline afforded the title compounds 7-12. The structures of the new compounds were confirmed by elemental analyses as well as H-1, C-13 NMR, IR and electronic spectral data. The HM1:IMSS strain of Entamoeba histolytica parasite was cultured in vitro and the sensitivity of the parasite to the synthesized compounds was evaluated using the microdilution method. Among all the pyrazoline derivatives 1-6, none was found to be a better inhibitor as compared to the reference drug, metronidazole. The quinoxaline derivatives, 9, 11 and 12 were found to be potent inhibitors of E. histolytica. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.116
• 作为产物：
  描述：

  3'-氯丙酮苯 在 盐酸 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 1.0h， 生成 3-(3-Chlorophenyl)-4-methyl-2-pyrazoline-1-thiocarboxamide
  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

文献信息

• Thio semicarbazone and semicarbazone inhibitors of cysteine proteases and methods of their use
  申请人：The Regents of the University of California

  公开号：US20040014801A1

  公开（公告）日：2004-01-22

  The present invention relates to thio semicarbazone and semicarbazone inhibitors of cysteine proteases and methods of using such compounds to prevent and treat protozoan infections such as trypanosomiasis, malaria and leishmaniasis. The compounds also find use in inhibiting cysteine proteases associated with carcinogenesis, including cathepsins B and L.

  本发明涉及硫代半卡巴酮和半卡巴酮对半胱氨酸蛋白酶的抑制剂，以及使用这些化合物预防和治疗原生动物感染，如锥虫病、疟疾和利什曼病的方法。这些化合物还可用于抑制与癌变有关的半胱氨酸蛋白酶，包括卡特普辛B和L。
• Thio semicarbazone and semicarbozone inhibitors of cysteine proteases and methods of their use
  申请人：Cohen E. Fred

  公开号：US20050182121A1

  公开（公告）日：2005-08-18

  The present invention relates to thio semicarbazone and semicarbazone inhibitors of cysteine proteases and methods of using such compounds to prevent and treat protozoan infections such as trypanosomiasis, malaria and leishmaniasis. The compounds also find use in inhibiting cysteine proteases associated with carcinogenesis, including cathepsins B and L.

  本发明涉及半胱氨酸蛋白酶的硫代半咔唑酮和半咔唑酮抑制剂，以及使用此类化合物预防和治疗原生动物感染（如锥虫病、疟疾和利什曼病）的方法。这些化合物还可用于抑制与致癌有关的半胱氨酸蛋白酶，包括酪蛋白 B 和 L。
• 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.
• US6897240B2
  申请人：——

  公开号：US6897240B2

  公开（公告）日：2005-05-24
• US7495023B2
  申请人：——

  公开号：US7495023B2

  公开（公告）日：2009-02-24