4-(4-乙苯基)-3-氨基硫脲 | 93693-01-7

• 物质功能分类: 化学试剂 - 有机试剂 - 硫脲
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(4-乙苯基)-3-氨基硫脲
• 中文别名: 4-4-乙苯基-3-氨基硫脲
• 英文名称: 4-(4-ethylphenyl)-3-thiosemicarbazide
• 英文别名: 4-(4-ethylphenyl)thiosemicarbazide；1-amino-3-(4-ethylphenyl)thiourea
• CAS: 93693-01-7
• 化学式: C₉H₁₃N₃S
• mdl: MFCD00041303
• 分子量: 195.288
• InChiKey: MXVVZBDSLDIVAW-UHFFFAOYSA-N

物化性质

• 熔点：
  128-131°C
• 沸点：
  314.5±35.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)
• 稳定性/保质期：

  避免与高温、火花、火焰、强还原剂或强氧化剂接触。

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  2

安全信息

• 危险等级：
  6.1
• 安全说明：
  S22,S36/37,S45
• 危险类别码：
  R25
• 危险品运输编号：
  UN 2811
• 海关编码：
  2930909090
• 包装等级：
  II
• 危险类别：
  6.1
• 储存条件：
  密封储存于阴凉、干燥的库房中，并远离热源和不相容材料。

反应信息

• 作为反应物：
  描述：

  4-(4-乙苯基)-3-氨基硫脲 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2-chloro-4-methyl-phenyl)-2-[[4-(4-ethylphenyl)-5-methyl-1,2,4-triazol-3-yl]sulfanyl]acetamide
  参考文献：
  名称：

  Tri-substituted triazoles as potent non-nucleoside inhibitors of the HIV-1 reverse transcriptase

  摘要：

  A new series of 1,2,4-triazoles was synthesized and tested against several NNRTI-resistant HIV-1 isolates. Several of these compounds exhibited potent antiviral activities against efavirenz- and nevirapine-resistant viruses, containing K103N and/or Y181C mutations or Y188L mutation. Triazoles were first synthesized from commercially available substituted phenylthio-semicarbazides, then from isothiocyanates, and later by condensing the desired substituted anilines with thiosemicarbazones. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.048
• 作为产物：
  描述：

  tert-butyl N-[(4-ethylphenyl)carbamothioylamino]carbamate 在 盐酸 作用下， 以 水 为溶剂， 生成 4-(4-乙苯基)-3-氨基硫脲
  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

• Nickel(II) Complexes with Polyhydroxybenzaldehyde and O,N,S tridentate Thiosemicarbazone ligands: Synthesis, Cytotoxicity, Antimalarial Activity, and Molecular Docking Studies
  作者：Savina Savir、Jonathan Wee Kent Liew、Indra Vythilingam、Yvonne Ai Lian Lim、Chun Hoe Tan、Kae Shin Sim、Vannajan Sanghiran Lee、Mohd. Jamil Maah、Kong Wai Tan

  DOI：10.1016/j.molstruc.2021.130815

  日期：2021.10

  which the Schiff base ligands bind to the metal centre via their tridentate O,N,S atoms. Ligand L2 and complex 1 showed a higher cytotoxic activity than cisplatin with IC50 5.75 ± 0.49 and 4.26 ± 0.29 μM, respectively when tested against human colorectal carcinoma HCT 116. Besides, complex 3 was found to show a stronger cytotoxic activity with an IC50 7.07 ± 0.61 μM than its ligand (L3 IC50 9.82 ± 1.85

  一系列 Schiff 贱金属配合物，具有 [Ni( L1 )PPh 3 ]Cl ( 1 )、[Ni( L2 )PPh 3 ]Cl ( 2 )、[Ni( L3 )PPh 3 ] ( 3 ) 和 [ Ni( L4 )PPh 3 ] ( 4 )（其中L1  = 2,3,4-三羟基苯甲醛-4-甲基-3-氨基硫脲，L2  = 2,3,4-三羟基苯甲醛-4-乙基-3-氨基硫脲，L3  = 2,3,4-三羟基苯甲醛-4-苯基-3-氨基硫脲和L4 = 2,3,4-三羟基苯甲醛-4-(4-乙基苯基)-3-氨基硫脲)被合成。所有化合物均使用 FT-IR、1 H NMR 和13 C NMR进行表征。用单晶 X 射线衍射进一步表征了配合物。这些配合物是四配位的，采用方形平面几何形状，其中希夫碱配体通过其三齿 O、N、S 原子与金属中心结合。当针对人结直肠癌 HCT 116 进行测试时，配体L2和复合物1显示出比顺铂更高的细胞毒活性，IC
• Synthesis and Urease Inhibitory Properties of Some New N4-Substituted 5-Nitroisatin-3-thiosemicarbazones
  作者：Humayun Pervez、Nazia Manzoor、Muhammad Yaqub、Ajmal Khan、Khalid Khan、Faiz-ul-Hassan Nasim、M. Choudhary

  DOI：10.2174/157018010790225840

  日期：2010.2.1

  with the synthesis and evaluation of urease inhibitory potential of a series of seventeen N 4 - arylsubstituted 5-nitroisatin-3-thiosemicarbazones. We describe here the effects of the nature of aryl groups at N 4 (modified by placement of one or two substituents about the phenyl ring) and the presence of nitro function at position-5 of the isatin scaffold on the urease inhibitory potential of these compounds

  4-取代的 5-nitroisatin-3-thiosemicarbazones 2a-2q 已被合成并筛选了体外脲酶抑制活性。发现化合物 2a-2d、2g、2i、2j 和 2q 是该酶的有效抑制剂。其中，2c 表现出有效的抑制活性，IC50 值为 16.4 μM，可作为进一步研究的先导分子。构效关系研究表明，取代基的电子效应在合成化合物的脲酶抑制潜力中起着重要作用。ery program (15-21), 我们最近合成了许多 N 4 - 取代的靛红-3-缩氨基硫脲作为脲酶抑制剂，具有无毒性质 (22, 23)。这些发现为进一步研究此类化合物以开发更有效、安全和有用的脲酶抑制剂奠定了坚实的基础。此外，构效关系 (SAR) 研究表明，苯环上取代基的类型和位置，在氨基硫脲部分的 N 4 处取代，在这些化合物的脲酶抑制潜力中起重要作用。为了进一步增强新的抗脲酶化合物的活性，研究了在靛红支架的 5
• Synthesis and Biological Evaluation of Some New N4-Aryl Substituted 5-Chloroisatin-3-thiosemicarbazones
  作者：Humayun Pervez、Muhammad Ramzan、Muhammad Yaqub、Faiz-ul-Hassan Nasim、Khalid Mohammed Khan

  DOI：10.2174/1573406411208030505

  日期：2012.5.1

  A new series of sixteen N4-aryl substituted 5-chloroisatin-3-thiosemicarbazones 2a-2p has been synthesized, characterized and tested for selected biological activities i.e. cytotoxicity, phytotoxicity and urease inhibition. In the brine shrimp bioassay, all the synthesized compounds gave LD50 values 2.30 X 10-4 M - 2.79 X 10-4 M and were, therefore, found to be almost inactive, whereas in phytotoxicity assay, regardless of the nature of aryl substituents, they displayed weak to moderate (5-40%) phytotoxic activity at the highest tested concentrations (500 or 1000 μg/mL). In urease inhibition bioassay, compounds 2a, 2c, 2e, 2f, 2k and 2m exhibited relatively a higher degree of urease inhibition with IC50 values ranging from 38.91 μM to 76.65 μM and thus proved to be potent inhibitors of the enzyme. Of these, 2f and 2m displayed pronounced inhibition with IC50 values 38.91 μM and 39.50 μM, respectively, and may act as lead compounds for further studies. Structure-activity relationship (SAR) studies revealed that electronic effects of the substituents about the phenyl ring at N4 of the thiosemicarbazone moiety played an important role in enhancing the urease inhibitory potential of some of the synthesized compounds.

  合成了一系列16种N4-芳基取代的5-氯靛红-3-缩氨基硫脲2a-2p，并对它们进行了表征和选择性生物活性测试，包括细胞毒性、植物毒性和脲酶抑制活性。在卤虫生物测定中，所有合成化合物的LD50值为2.30 X 10-4 M至2.79 X 10-4 M，因此被发现几乎无活性；而在植物毒性测定中，无论芳基取代基的性质如何，它们在最高测试浓度（500或1000 μg/mL）下表现出微弱至中等的（5-40%）植物毒性活性。在脲酶抑制生物测定中，化合物2a、2c、2e、2f、2k和2m表现出较高的脲酶抑制程度，IC50值范围为38.91 μM至76.65 μM，证明了它们是该酶的有效抑制剂。其中，2f和2m表现出显著的抑制作用，IC50值分别为38.91 μM和39.50 μM，可能作为进一步研究的先导化合物。结构-活性关系（SAR）研究表明，缩氨基硫脲部分N4位苯环上的取代基的电子效应对某些合成化合物的脲酶抑制潜力起着重要作用。
• Synthesis, Cytotoxic and Phytotoxic Effects of Some New N4-Aryl Substituted Isatin-3-thiosemicarbazones
  作者：Humayun Pervez、Muhammad Ramzan、Muhammad Yaqub、Khalid Mohammed Khan

  DOI：10.2174/157018011795514159

  日期：2011.6.1

  A series of N4-aryl substituted isatin-3-thiosemicarbazones was prepared by the reaction of isatin with an appropriate thiosemicarbazide in ethanol containing a few drops of acetic acid. The newly synthesized compounds were characterized by means of their analytical (CHN) and spectral (IR, 1H-NMR, EIMS) data, and evaluated for their cytotoxicity and phytotoxicity potential. Eleven out of thirteen compounds tested proved to be active in the brine-shrimp lethality bioassay exhibiting significant cytotoxic activity with LD50 values ranging from 1.75x10-5M to 1.91x10-4M. In phytotoxicity assay, all the synthesized compounds, regardless of the nature of aryl substituents, demonstrated weak to moderate (5-30%) plant growth inhibition at the highest tested concentration (500 μg/mL).

  一系列N4-芳基取代的异吲哚-3-硫半卡巴脒通过异吲哚与适当的硫脲在含有几滴醋酸的乙醇中反应制备。新合成的化合物通过其分析（CHN）和谱学（IR、1H-NMR、EIMS）数据进行表征，并评估了它们的细胞毒性和植物毒性潜力。在十三种测试的化合物中，有十一种在卤虫 lethality 生物测定中表现出显著的细胞毒活性，LD50值范围从1.75x10-5M到1.91x10-4M。在植物毒性测定中，所有合成的化合物，无论芳基取代基的性质如何，在最高测试浓度（500 μg/mL）下均表现出轻微至中等（5-30%）的植物生长抑制作用。
• Synthesis and antiproliferative activity of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles
  作者：Joanna Matysiak、Adam Opolski

  DOI：10.1016/j.bmc.2006.02.027

  日期：2006.7

  A number of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles were synthesized and evaluated for their antiproliferative activities. The panel substitution included alkyl, aryl, and morpholinoalkyl derivatives. The structures of compounds were identified from elemental, IR, (1)H NMR, (13)C NMR and MS spectra analyses. The cytotoxicity in vitro against the four human cell lines: SW707

  合成了许多N-取代的2-氨基-5-（2,4-二羟基苯基）-1,3,4-噻二唑并评估了它们的抗增殖活性。面板取代包括烷基，芳基和吗啉代烷基衍生物。化合物的结构由元素，IR，（1）H NMR，（13）C NMR和MS光谱分析确定。确定了对四种人类细胞系的体外细胞毒性：SW707（直肠），HCV29T（膀胱），A549（肺）和T47D（乳腺癌）。烷基和吗啉代烷基衍生物显示出比苯基显着更低的作用。发现2-（2,4-二氯苯基氨基）-5-（2,4-二羟基苯基）-1,3,4-噻二唑具有最高的抗增殖活性，ID（50）的抗增殖活性比SW（T707D）低2倍。顺铂作为对照化合物进行了比较研究。