4-[4-(三氟甲基)苯基]-3-硫代氨基脲 | 206761-90-2

• 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-(三氟甲基)苯基]-3-硫代氨基脲
• 中文别名: 4-[4-(三氟甲基)苯基]-3-氨基硫脲
• 英文名称: N-(4-(trifluoromethyl)phenyl)hydrazinecarbothioamide
• 英文别名: 4-(4-(trifluoromethyl)phenyl)-3-thiosemicarbazide；4-(4-(trifluoromethyl)phenyl)thiosemicarbazide；4-trifluorophenyl thiosemicarbazide；4-[4-(Trifluoromethyl)phenyl]-3-thiosemicarbazide；1-amino-3-[4-(trifluoromethyl)phenyl]thiourea
• CAS: 206761-90-2
• 化学式: C₈H₈F₃N₃S
• mdl: MFCD00041301
• 分子量: 235.233
• InChiKey: NWPGZYRPTJGBPI-UHFFFAOYSA-N

物化性质

• 熔点：
  171-172°C (dec.)
• 沸点：
  290.4±50.0 °C(Predicted)
• 密度：
  1.471±0.06 g/cm3(Predicted)
• 稳定性/保质期：

  避用氧化剂和还原剂。

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 危险等级：
  6.1
• 危险品标志：
  Xi
• 危险类别码：
  R22
• 危险品运输编号：
  2811
• 海关编码：
  2930909090
• 包装等级：
  III
• 危险类别：
  6.1
• 安全说明：
  S26,S36/37/39
• 储存条件：
  保存方法：密封于阴凉、通风且干燥的地方。

反应信息

• 作为反应物：
  描述：

  4-[4-(三氟甲基)苯基]-3-硫代氨基脲 在 盐酸 、 lithium aluminium tetrahydride 、 硫酸 作用下， 以 四氢呋喃 为溶剂， 反应 4.42h， 生成 [5-Methyl-3-(4-trifluoromethyl-phenylamino)-1H-pyrazol-4-yl]-methanol
  参考文献：
  名称：

  Pyrazole Bioisosteres of Leflunomide as B-Cell Immunosuppressants for Xenotransplantation and Chronic Rejection:  Scope and Limitations

  摘要：

  T-cell immunosuppressant-based therapies efficiently control early graft rejection in allotransplantation settings. They fail, however, to prevent those rejection events which are mediated by transplant-induced antibody (Ab) responses such as those involved in xenograft and chronic allograft rejection. This is mainly due to their inability to block T-cell-independent Ab production against the transplanted organs. The bioactive metabolite 2(Z) of leflunomide (1) inhibits the formation of such Ab, but the drug has pharmacokinetic properties and a therapeutic window incompatible with transplantation indications. Pyrazole 3, a constrained analogue of 2(Z), was designed and shown to be conformationally and biologically similar to 2(Z). Further investigations with derivatives of 3 demonstrated that the pyrazoles had very tight structure-activity relationships, the only equipotent compound being 3o. However, in contrast to 2(Z), both 3 and 3o were inactive in vivo due to short half-life and drug concentrations lower than the in vitro obtained IC50 values, Compound 3o inhibits T-cell-independent Ab production by a different biochemical mechanism from that of 2(Z) and 3 and may therefore represent a valuable tool for the identification of new targets for B-cell inhibition.

  DOI：

  10.1021/jm981028c
• 作为产物：
  描述：

  在 肼 作用下， 生成 4-[4-(三氟甲基)苯基]-3-硫代氨基脲
  参考文献：
  名称：

  发现口服活性吡唑并喹啉作为有效的PDE10抑制剂可用于精神分裂症的治疗

  摘要：

  已合成了一系列吡唑并喹啉类似物，并显示出与PDE10的高亲和力结合。通过SAR研究和我们的前导优化工作，发现化合物16和27在MK-801诱导的多动症大鼠模型中具有有效的口服抗精神病活性。

  DOI：

  10.1016/j.bmcl.2011.11.023

文献信息

• 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
• Novel metal chelators thiosemicarbazones with activity at the σ₂receptors and P-glycoprotein: an innovative strategy for resistant tumor treatment
  作者：Maria Laura Pati、Mauro Niso、Savina Ferorelli、Carmen Abate、Francesco Berardi

  DOI：10.1039/c5ra19857g

  日期：——

  Novel multitarget thiosemicarbazones that bind simultaneously σ₂receptors and P-glycoprotein efflux pump and chelate metals were designed for resistant tumors treatment.

  设计了一种新型的多靶点噻唑半胱氨酮，可以同时结合σ₂受体和P-糖蛋白外流泵，并螯合金属，用于治疗耐药肿瘤。
• Synthesis and Toxicity Evaluation of Some N4-Aryl Substituted 5-Trifluoromethoxyisatin-3-thiosemicarbazones
  作者：Humayun Pervez、Naveeda Saira、Mohammad Saeed Iqbal、Muhammad Yaqub、Khalid Mohammed Khan

  DOI：10.3390/molecules16086408

  日期：——

  A series of twenty one N4-aryl substituted 5-trifluoromethoxyisatin-3-thiosemicarbazones 3a-3u was synthesized by the reaction of trifluoromethoxyisatin 1 with different arylthiosemicarbazides 2 in aqueous ethanol (50%), containing a few drops of acetic acid. Their structures were established on the basis of analytical (CHN) and spectral (IR, 1H-NMR, EIMS) data. All the synthesized compounds were evaluated for their toxicity potential by a brine shrimp lethality bioassay. Ten compounds i.e., 3a, 3e, 3i-3l and 3n-3q proved to be active in this assay, displaying promising toxicity (LD50 = 1.11 × 10−5 M − 1.80 × 10−4 M). Amongst these, 3k, 3n and 3o were found to be the most active ones (LD50 = 1.11 × 10−5 M − 1.43 × 10−5 M). Compound 3k showed the highest activity with a LD50 value of 1.11 × 10−5 M and can, therefore, be used as a lead for further studies. Structure-activity relationship (SAR) studies revealed that the presence of strong inductively electron-attracting trifluoromethoxy substituent at position-5 of the isatin moiety played an important role in inducing or enhancing toxic potentiality of some of the synthesized compounds.

  通过三氟甲氧基异吲哚1与不同芳基缩氨基脲2在含有几滴醋酸的50%乙醇水溶液中的反应，合成了一系列21种N4-芳基取代的5-三氟甲氧基异吲哚-3-缩氨基脲3a-3u。它们的结构是基于分析（CHN）和光谱（IR，1H-NMR，EIMS）数据确定的。所有合成的化合物都通过卤虫致死生物测定法评估了它们的毒性潜力。其中10种化合物，即3a，3e，3i-3l和3n-3q在此测定中表现活跃，显示出有前景的毒性（LD50 = 1.11 × 10−5 M − 1.80 × 10−4 M）。在这些化合物中，3k，3n和3o被发现是最活跃的（LD50 = 1.11 × 10−5 M − 1.43 × 10−5 M）。化合物3k显示出最高的活性，其LD50值为1.11 × 10−5 M，因此可以作为进一步研究的先导化合物。构效关系（SAR）研究表明，在异吲哚部分的5位上存在强诱导电子吸引的三氟甲氧基取代基，在诱导或增强某些合成化合物的毒性潜力方面发挥了重要作用。
• Synthesis of substituted 3-(5-amino-[1,3,4]thiadiazol-2-yl)-2<i>H</i>-pyrano[2,3-<i>c</i>]pyridin-2-ones
  作者：Irina O. Zhuravel'、Sergiy M. Kovalenko、Alexandre V. Ivachtchenko、Valentin P. Chernykh、Pavlo E. Shinkarenko

  DOI：10.1002/jhet.5570410407

  日期：2004.7

  An efficient two-step synthesis of novel 3-(5-amino-[1,3,4]thiadiazol-2-yl)-2H-pyrano[2,3-c]pyridine-2-ones was developed. In the first step, a new 2H-pyrano[2,3-c]pyridine-3-carboxamide 5 was prepared by Knoevenagel condensation of pyridoxal hydrochloride with cyanoacetamide. In the second step, the reaction of carboxamide 5 with a series of N4-substituted thiosemicarbazides yielded a library of 35

  开发了有效的两步合成新型3-（5-氨基-[1,3,4]噻二唑-2-基）-2 H-吡喃并[2,3 - c ]吡啶-2-酮。第一步，通过吡pyr醛盐酸盐与氰基乙酰胺的Knoevenagel缩合制备新的2 H-吡喃并[2,3 - c ]吡啶-3-甲酰胺5。在第二步中，羧酰胺5与一系列N 4取代的硫代氨基脲的反应以高收率产生了35种离散化合物8 1-35}的库。讨论了导致这些产物的分子间再循环机理。
• Synthesis of novel spiro(indolone-3,2′-[1,3,4]thiadiazol)-2-ones and evaluation of their antidepressant and anticonvulsant activities
  作者：Alaa A. Hassan、Fathy F. Abdel-Latif、Ahmed M. Nour El-Din、Mohamed Abdel-Aziz、Sara M. Mostafa、Stefan Bräse

  DOI：10.1002/jhet.687

  日期：2011.9

  derivatives of 5′‐(substituted amino)‐3′H–spiro(indoline‐3,2′‐[1,3,4]thiadiazol‐2‐one. Rationales for these conversions involving the nucleophilic addition on the dicyanomethylene carbon atom are presented. The prepared compounds were evaluated each for antidepressant activity using tail suspension behavioral despair test and anticonvulsant activity against pentylenetetrazol induced seizures in mice. J. Heterocyclic

  的3-反应（二氰基亚）-2-吲哚酮在乙醇/哌啶与4-取代的氨基硫脲溶液形成5的衍生物' - （取代的氨基）-3' ħ -螺（二氢吲哚-3,2' - [ 1,3,4]噻二唑-2-酮。这些转化涉及在二氰基亚甲基碳原子上进行亲核加成反应的原理，并通过尾部悬浮行为绝望测试评估了所制备的化合物的抗抑郁活性以及对戊四氮诱发癫痫发作的抗惊厥活性。 J. Heterocyclic Chem。，（2011）。