4-chloro-6-(5-(4-fluorophenylamino)-1,3,4-thiadiazol-2-yl)benzene-1,3-diol | 1447735-11-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-chloro-6-(5-(4-fluorophenylamino)-1,3,4-thiadiazol-2-yl)benzene-1,3-diol
• 英文别名: 4-Chloro-6-(5-(4-fluorophenylamino)-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (14)；4-chloro-6-[5-(4-fluoroanilino)-1,3,4-thiadiazol-2-yl]benzene-1,3-diol
• CAS: 1447735-11-6
• 化学式: C₁₄H₉ClFN₃O₂S
• 分子量: 337.762
• InChiKey: GCEMYRRTENOITQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  sulfinylbis[(5-chloro-2,4-dihydroxyphenyl)methanethione] 、 4-(4-氟苯)-3-氨基硫脲 以 甲醇 为溶剂， 生成 4-chloro-6-(5-(4-fluorophenylamino)-1,3,4-thiadiazol-2-yl)benzene-1,3-diol
  参考文献：
  名称：

  作为多功能胆碱酯酶抑制剂的新型 1,3,4-噻二唑-间苯二酚偶联物的生物学评价和分子对接

  摘要：

  两个系列的新型 1,3,4-噻二唑-间苯二酚偶联物被有效合成并评估为胆碱酯酶抑制剂。N-丁基-和N-氯苯基-5-氨基-1,3,4-噻二唑-2-基)苯-1,3-二醇被确定为最有前途的化合物，对 AChE 具有低纳摩尔活性 (IC 50 = 29–76 nM) 和对 BuChE 的中等活性。抑制机理研究证明该化合物为混合型抑制剂。对接模拟显示化合物对两种酶都有很大的亲和力。模拟的胺衍生物在 AChE 的催化阴离子位点中表现出与他克林相似的排列。噻二唑环与 Trp84 相互作用，苯基与残基 Phe330 产生 π-π 堆积相互作用。与姜黄素相比，这些化合物显示出更好的体外自诱导 Aβ (1-42) 聚集抑制作用，以及与槲皮素相似的抗氧化特性。它们显示金属离子螯合性能，可接受的细胞毒性在体外和favourabl Ë在计算机中确定的 ADMET 配置文件。

  DOI：

  10.1016/j.bioorg.2020.104617

文献信息

• Synthesis and anticholinesterase activities of novel 1,3,4-thiadiazole based compounds
  作者：Alicja Skrzypek、Joanna Matysiak、Monika M. Karpińska、Andrzej Niewiadomy

  DOI：10.3109/14756366.2012.688041

  日期：2013.8.1

  In the present study, new (1,3,4-thiadiazol-2-yl)benzene-1,3-diol based compounds have been synthesized and their potential anticholinesterases properties have been investigated using the modified of Ellman's spectrophotometric method. The compounds were obtained by the reaction of hydrazides or thiosemicarbazides with aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]s. Their chemical structures

  在本研究中，已合成了新的（1,3,4-噻二唑-2-基）苯-1,3-二醇基化合物，并使用改进的Ellman分光光度法研究了其潜在的抗胆碱酯酶特性。通过使酰肼或硫代氨基脲与芳基改性的亚磺酰基双[（2,4-二羟基苯基）甲烷硫酮]反应获得化合物。通过IR，（1）H-NMR，（13）C-NMR和EI-MS光谱数据和元素分析来阐明它们的化学结构。多数化合物在体外起乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）抑制剂的作用，IC 50值分别为> 500至0.053μM和> 500至0.105μM。事实证明，最有效的化合物9（IC 50 = 0.053μM）对AChE具有选择性，相对于BuChE的选择性比约为。950。动力学研究表明，它是混合型的AChE抑制剂。另一种化合物（2）对两种酶都具有活性，IC 50值在低nM范围内。讨论了所考虑化合物的构效关系（SAR）。
• Design, synthesis and biological evaluation of novel 1,3,4-thiadiazole derivatives as anti-glioblastoma agents targeting the AKT pathway
  作者：Monika Szeliga、Monika Karpińska、Radosław Rola、Andrzej Niewiadomy

  DOI：10.1016/j.bioorg.2020.104362

  日期：2020.12

  In spite of progress in understanding biology of glioblastoma (GBM), this tumor remains incurable with a median survival rate of 15 months. Previous studies have shown that 2-(4-fluorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (FPDT) and 2-(3-chlorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (CPDT) diminished viability of cancer cell lines of different origin. In the current study, we have examined activity of these compounds in several GBM cell lines and patient-derived GBM cells. We have also designed, synthesized and evaluated anti-GBM activity of novel 1,3,4-thiadiazole derivatives containing additional Cl or CH₂CH₃ substitute at C5-position of 2,4-dihydroxyphenyl. The tested compounds presented a considerable cytotoxicity against all GBM cell lines examined as well as patient-derived GBM cells. They were 15-110 times more potent than temozolomide, the first-line chemotherapeutic agent for GBM. Notably, in anticancer concentrations three of the derivatives were not toxic to human astrocytes. FPDT appeared to be the most promising compound with IC₅₀ values between 45 μM and 68 μM for GBM cells and >100 μM for astrocytes. It augmented activity of temozolomide and inhibited proliferation migration and invasion of GBM cells. Treatment with FPDT diminished phosphorylation level of GSK3β and AKT. Pretreatment with PDGF-BB, an AKT activator, partially protected cells from death caused by FPDT, indicating that FPDT-mediated decrease in cell viability is causatively related to the inhibition of the AKT pathway.