4-(3',4',5'-trifluorophenyl)-3-thiosemicarbazide | 1318765-46-6

• 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: 4-(3',4',5'-trifluorophenyl)-3-thiosemicarbazide
• 英文别名: 1-Amino-3-(3,4,5-trifluorophenyl)thiourea
• CAS: 1318765-46-6
• 化学式: C₇H₆F₃N₃S
• 分子量: 221.206
• InChiKey: FKKKLZUBEWWGIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3',4',5'-trifluorophenyl)-3-thiosemicarbazide 、 靛红 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 0.75h， 生成 1-isatin-4-(3',4',5'-trifluorophenyl)-3-thiosemicarbazone
  参考文献：
  名称：

  [EN] THIOSEMICARBAZONES WITH MDR1 - INVERSE ACTIVITY
  [FR] THIOSEMICARBAZONES À ACTIVITÉ ANTI-MDR1

  摘要：

  本文披露了具有MDR逆转活性的药物化合物，因此对多药耐药细胞有效。本文披露的示例化合物具有下列结构；公式（I）。已发现披露的化合物的示例具有直接治疗多药耐药细胞的功效，使多药耐药细胞对其他化疗药物敏感，并在某些情况下逆转多药耐药。

  公开号：

  WO2012033601A1
• 作为产物：
  描述：

  在 盐酸 作用下， 以 水 为溶剂， 生成 4-(3',4',5'-trifluorophenyl)-3-thiosemicarbazide
  参考文献：
  名称：

  Synthesis and Structure–Activity Evaluation of Isatin-β-thiosemicarbazones with Improved Selective Activity toward Multidrug-Resistant Cells Expressing P-Glycoprotein

  摘要：

  Cancer multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters presents a significant unresolved clinical challenge. One strategy to resolve MDR is to develop compounds that selectively kill cells overexpressing the efflux transporter P-glycoprotein (MDR1, P-gp, ABCB1). We have previously reported structure-activity studies based around the lead compound NSC73306 (1, 1-isatin-4-(4'-methoxyphenyl)-3-thiosemicarbazone, 4.3-fold selective). Here we sought to extend this work on MDR1-selective analogues by establishing whether 1 showed "robust" activity against a range of cell lines expressing P-gp. We further aimed to synthesize and test analogues with varied substitution at the N4-position, and substitution around the N4-phenyl ring of isatin-beta-thiosemicarbazones (IBTs), to identify compounds with increased MDR1-selectivity. Compound 1 demonstrated MDR1-selectivity against all P-gp-expressing cell lines examined. This selectivity was reversed by inhibitors of P-gp ATPase activity. Structural variation at the 4'-phenyl position of 1 yielded compounds of greater MDR1-selectivity. Two of these analogues, 1-isatin-4-(4'-nitrophenyl)-3-thiosemicarbazone (22, 8.3-fold selective) and 1-isatin-4-(4'-tert-butyl phenyl)-3-thiosemicarbazone (32, 14.8-fold selective), were selected for further testing and were found to retain the activity profile of 1. These compounds are the most active IBTs identified to date.

  DOI：

  10.1021/jm2006047

文献信息

• Halide-selective, proton-coupled anion transport by phenylthiosemicarbazones
  作者：Ethan N.W. Howe、Vai-Vai Tiffany Chang、Xin Wu、Mohamed Fares、William Lewis、Lauren K. Macreadie、Philip A. Gale

  DOI：10.1016/j.bbamem.2021.183828

  日期：2022.2

  proton-coupled anion transporters with pH-switchable behaviour known to be regulated by an imine protonation equilibrium. Previously, chloride/nitrate exchange by PTSCs was found to be inactive at pH 7.2 due to locking of the thiourea anion binding site by an intramolecular hydrogen bond, and switched ON upon imine protonation at pH 4.5. The rate-determining process of the pH switch, however, was not

  Phenylthiosemicarbazones (PTSCs) 是质子偶联的阴离子转运蛋白，具有已知受亚胺质子化平衡调节的 pH 可切换行为。以前，由于硫脲阴离子结合位点被分子内氢键锁定，PTSCs 的氯化物/硝酸盐交换在 pH 7.2 时被发现是无活性的，并且在 pH 4.5 时打开亚胺质子化。然而，没有检查 pH 转换的速率决定过程。我们在这里开发了一系列新的 PTSC，并通过 X 射线晶体学分析证明了它们的构象行为，并通过脂质体测定证明了它们的 pH 可切换阴离子转运特性。我们报告了一个令人惊讶的发现，即质子化的 PTSC 在膜运输中对卤化物的选择性高于氧阴离子。由于对硝酸盐的高氯化物选择性，
• Synthesis and Structure–Activity Evaluation of Isatin-β-thiosemicarbazones with Improved Selective Activity toward Multidrug-Resistant Cells Expressing P-Glycoprotein
  作者：Matthew D. Hall、Kyle R. Brimacombe、Matthew S. Varonka、Kristen M. Pluchino、Julie K. Monda、Jiayang Li、Martin J. Walsh、Matthew B. Boxer、Timothy H. Warren、Henry M. Fales、Michael M. Gottesman

  DOI：10.1021/jm2006047

  日期：2011.8.25

  Cancer multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters presents a significant unresolved clinical challenge. One strategy to resolve MDR is to develop compounds that selectively kill cells overexpressing the efflux transporter P-glycoprotein (MDR1, P-gp, ABCB1). We have previously reported structure-activity studies based around the lead compound NSC73306 (1, 1-isatin-4-(4'-methoxyphenyl)-3-thiosemicarbazone, 4.3-fold selective). Here we sought to extend this work on MDR1-selective analogues by establishing whether 1 showed "robust" activity against a range of cell lines expressing P-gp. We further aimed to synthesize and test analogues with varied substitution at the N4-position, and substitution around the N4-phenyl ring of isatin-beta-thiosemicarbazones (IBTs), to identify compounds with increased MDR1-selectivity. Compound 1 demonstrated MDR1-selectivity against all P-gp-expressing cell lines examined. This selectivity was reversed by inhibitors of P-gp ATPase activity. Structural variation at the 4'-phenyl position of 1 yielded compounds of greater MDR1-selectivity. Two of these analogues, 1-isatin-4-(4'-nitrophenyl)-3-thiosemicarbazone (22, 8.3-fold selective) and 1-isatin-4-(4'-tert-butyl phenyl)-3-thiosemicarbazone (32, 14.8-fold selective), were selected for further testing and were found to retain the activity profile of 1. These compounds are the most active IBTs identified to date.
• [EN] THIOSEMICARBAZONES WITH MDR1 - INVERSE ACTIVITY<br/>[FR] THIOSEMICARBAZONES À ACTIVITÉ ANTI-MDR1
  申请人：US HEALTH

  公开号：WO2012033601A1

  公开（公告）日：2012-03-15

  Disclosed herein are drug compounds that have MDR-inverse activity and thus are effective against multidrug-resistant cells. Exemplary compounds disclosed herein have the structure;Formula (I). Examples of the disclosed compounds have been found to have, inter alia, efficacy in directly treating multidrug resistant cells, rendering multidrug resistant cells susceptible to other chemotherapeutics and in some instances reversing multidrug resistance.

  本文披露了具有MDR逆转活性的药物化合物，因此对多药耐药细胞有效。本文披露的示例化合物具有下列结构；公式（I）。已发现披露的化合物的示例具有直接治疗多药耐药细胞的功效，使多药耐药细胞对其他化疗药物敏感，并在某些情况下逆转多药耐药。