3-trifluoromethylbenzaldehyde thio semicarbazone

• 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-trifluoromethylbenzaldehyde thio semicarbazone
• 英文别名: (2E)-2-[3-(trifluoromethyl)benzylidene]hydrazinecarbothioamide；[(E)-[3-(trifluoromethyl)phenyl]methylideneamino]thiourea
• 化学式: C₉H₈F₃N₃S
• 分子量: 247.244
• InChiKey: GDIMOASDCOFPTD-LHHJGKSTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-trifluoromethylbenzaldehyde thio semicarbazone 、 三氯化铁 生成 5-(3-(trifluoromethyl)phenyl)-1,3,4-thiadiazol-2-amine
  参考文献：
  名称：

  TURNER, STEPHEN;MYERS, MALCOLM;GADIE, BRIAN;NELSON, ANTHONY J.;PAPE, ROBI+, J. MED. CHEM., 31,(1988) N 5, 902-906

  摘要：

  DOI：
• 作为产物：
  描述：

  3-三氟甲基苯甲醛 、 氨基硫脲 以 甲醇 为溶剂， 反应 3.0h， 生成 3-trifluoromethylbenzaldehyde thio semicarbazone
  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

• EP1399159A4
  申请人：——

  公开号：EP1399159A4

  公开（公告）日：2007-02-14
• 4-SUBSTITUTED-1-(ARYLMETHYLIDENE)THIOSEMICARBAZIDE, 4-SUBSTITUTED-1-(ARYLCARBONYL)THIOSEMICARBAZIDE AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cytovia, Inc.

  公开号：EP1399159A1

  公开（公告）日：2004-03-24
• [EN] 4-SUBSTITUTED-1-(ARYLMETHYLIDENE)THIOSEMICARBAZIDE, 4-SUBSTITUTED-1-(ARYLCARBONYL)THIOSEMICARBAZIDE AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF<br/>[FR] 4-SUBSTITUTE-1-(ARYLMETHYLIDENE)THIOSEMICARBAZIDE, 4-SUBSTITUE-1-(ARYLCARBONYL)THIOSEMICARBAZIDE ET ANALOGUES EN TANT QU'ACTIVATEURS DE CAPSASES ET DECLENCHEURS D'APOPTOSE, ET LEUR UTILISATION
  申请人：CYTOVIA INC

  公开号：WO2002098420A1

  公开（公告）日：2002-12-12

  The present invention is directed to optionally substituted 4-substituted-1-(arylmethylidene)thiosemicarbazide, 4-substituted-1-(arylcarbonyl)thiosemicarbazide and analogs thereof, represented by the Formulae (I) and (II), wherein A1, A2, Q and R1-R3 are defined herein. The present invention also relates to the discovery that compounds having Formulae (I) and (II) are activators o f caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.