5-(1-naphthylmethyl)-1,3,4-thiadiazol-2-amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-(1-naphthylmethyl)-1,3,4-thiadiazol-2-amine
• 英文别名: 5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-amine；5-Naphthalen-1-ylmethyl-[1,3,4]thiadiazol-2-ylamine
• 化学式: C₁₃H₁₁N₃S
• mdl: MFCD01131204
• 分子量: 241.316
• InChiKey: FZBLLTOCSPCNAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  80
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(1-naphthylmethyl)-1,3,4-thiadiazol-2-amine 在 ammonium acetate 、 sodium methylate 、 溶剂黄146 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 8.33h， 生成 (E)-2-(2-cyano-3-((5-(naphthalene-1-ylmethyl)-1,3,4-thiadiazol-2-yl)amino)-3-oxoprop-1-en-1-yl)phenyl 4-fluorobenzenesulfonate
  参考文献：
  名称：

  Synthesis of (1,3,4-thiadiazol-2-yl)-acrylamide derivatives as potential antitumor agents against acute leukemia cells

  摘要：

  A lead compound with the (1,3,4-thiadiazol-2-yl) acrylamide scaffold was discovered to have significant cytotoxicity on several tumor cell lines in an in-house cell-based screening. A total of 60 derivative compounds were then synthesized and tested in a CCK-8 cell viability assay. Some of them exhibited improved cytotoxic activities. The most potent compounds had IC50, values of 1-5 mu M on two acute leukemia tumor cell lines, i.e. RS4;11 and HL-60. Flow cytometry analysis of several active compounds and detection of caspase activation indicated that they induced caspase-dependent apoptosis. It was also encouraging to observe that these compounds did not have obvious cytotoxicity on normal cells, i.e. IC50 > 50 mu M on HEK-293T cells. Although the molecular targets of this class of compound are yet to be revealed, our current results suggest that this class of compound represents a new possibility for developing drug candidates against acute leukemia.

  DOI：

  10.1016/j.bmcl.2020.127114
• 作为产物：
  描述：

  1-萘乙酸 、 氨基硫脲 在 硫酸 作用下， 反应 8.0h， 以70%的产率得到5-(1-naphthylmethyl)-1,3,4-thiadiazol-2-amine
  参考文献：
  名称：

  某些新型2-（萘-1-基）-甲基咪唑并[2,1- b ] [1,3,4]噻二唑的合成，分子对接和初步细胞毒性研究

  摘要：

  制备了一系列2-（萘-1-基）-甲基-6-芳基咪唑[2,1- b ] [1,3,4]噻二唑衍生物，并研究了其对鼠白血病L1210，人宫颈癌HeLa的细胞毒性，和人类T淋巴细胞CEM细胞系。初步研究表明，化合物5g，6g，7a-c，7e和8e在受试化合物中更有效。然后使用FAF-Drugs（一种用于预测ADME和毒性的工具）研究所有化合物的药代动力学特性。最后，以支持体外研究中，分子对接研究是通过使用AutoDock Vina和Lamarckian遗传算法进行的，以确定合成的化合物是否可用作1m17蛋白结构（EGFR）的抑制剂。发现许多化合物的对接得分都高于1m17 EGFR受体抑制剂[6,7-双（2-甲氧基-乙氧基）喹唑啉-4-基]-（3-乙炔基苯基）胺。在分子动力学模拟研究中，所选化合物7b，7c，7e，7f，7g和8g显示出更好的稳定性。

  DOI：

  10.1016/j.molstruc.2021.130174

文献信息

• Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure–Activity Relationship Study
  作者：Matthias Schiedel、Tobias Rumpf、Berin Karaman、Attila Lehotzky、Judit Oláh、Stefan Gerhardt、Judit Ovádi、Wolfgang Sippl、Oliver Einsle、Manfred Jung

  DOI：10.1021/acs.jmedchem.5b01517

  日期：2016.2.25

  Here, we present a well-defined structure–activity relationship study, which rationalizes the unique features of the SirReals and probes the limits of modifications on this scaffold regarding inhibitor potency. Moreover, we present a crystal structure of hSirt2 in complex with an optimized SirReal derivative that exhibits an improved in vitro activity. Lastly, we show cellular hyperacetylation of the

  Sirtuins是NAD +-依赖性蛋白脱酰基酶，其从组蛋白和其他底物蛋白中的赖氨酸的ε-氨基上裂解掉乙酰基以及其他酰基。人类Sirt2（hSirt2）活性的失调与癌症，炎症和神经退行性病变的发病机制有关，这使得对hSirt2活性的调节成为药物干预的有前途的策略。sirtuin重排配体（SirReals）最近已被我们发现为高效且同型选择性的hSirt2抑制剂。在这里，我们提出了一个定义明确的结构-活性关系研究，该研究合理化了SirReals的独特功能，并探讨了该支架在抑制剂效能方面的修饰极限。而且，我们提出了具有优化的SirReal衍生物的hSirt2晶体结构，该衍生物具有改善的体外活性。最后，我们显示了由我们改良的前导结构导致的hSirt2靶向微管蛋白的细胞过度乙酰化。
• Synthesis, molecular docking, and preliminary cytotoxicity study of some novel 2-(naphthalen-1-yl)-methylimidazo[2,1-b][1,3,4]thiadiazoles
  作者：Choodamani B、Sujeet Kumar、Alok Kumar Gupta、Dominique Schols、Hakan Tahtaci、Tuncay Karakurt、Satvik Kotha、Swapna B、Ramachandra Setty、Subhas S. Karki

  DOI：10.1016/j.molstruc.2021.130174

  日期：2021.6

  A series of 2-(naphthalen-1-yl)-methyl-6-arylimidazo[2,1-b][1,3,4]thiadiazole derivatives was prepared and studied for cytotoxicity against murine leukemia L1210, human cervix carcinoma HeLa, and human T-lymphocyte CEM cell lines. The preliminary study showed that compounds 5g, 6g, 7a-c, 7e, and 8e were more potent among the tested compounds. The pharmacokinetic properties of all compounds were then

  制备了一系列2-（萘-1-基）-甲基-6-芳基咪唑[2,1- b ] [1,3,4]噻二唑衍生物，并研究了其对鼠白血病L1210，人宫颈癌HeLa的细胞毒性，和人类T淋巴细胞CEM细胞系。初步研究表明，化合物5g，6g，7a-c，7e和8e在受试化合物中更有效。然后使用FAF-Drugs（一种用于预测ADME和毒性的工具）研究所有化合物的药代动力学特性。最后，以支持体外研究中，分子对接研究是通过使用AutoDock Vina和Lamarckian遗传算法进行的，以确定合成的化合物是否可用作1m17蛋白结构（EGFR）的抑制剂。发现许多化合物的对接得分都高于1m17 EGFR受体抑制剂[6,7-双（2-甲氧基-乙氧基）喹唑啉-4-基]-（3-乙炔基苯基）胺。在分子动力学模拟研究中，所选化合物7b，7c，7e，7f，7g和8g显示出更好的稳定性。
• Synthesis of (1,3,4-thiadiazol-2-yl)-acrylamide derivatives as potential antitumor agents against acute leukemia cells
  作者：Qing Li、Ran An、Yaochun Xu、Mi Zhou、Yan Li、Chun Guo、Renxiao Wang

  DOI：10.1016/j.bmcl.2020.127114

  日期：2020.5

  A lead compound with the (1,3,4-thiadiazol-2-yl) acrylamide scaffold was discovered to have significant cytotoxicity on several tumor cell lines in an in-house cell-based screening. A total of 60 derivative compounds were then synthesized and tested in a CCK-8 cell viability assay. Some of them exhibited improved cytotoxic activities. The most potent compounds had IC50, values of 1-5 mu M on two acute leukemia tumor cell lines, i.e. RS4;11 and HL-60. Flow cytometry analysis of several active compounds and detection of caspase activation indicated that they induced caspase-dependent apoptosis. It was also encouraging to observe that these compounds did not have obvious cytotoxicity on normal cells, i.e. IC50 > 50 mu M on HEK-293T cells. Although the molecular targets of this class of compound are yet to be revealed, our current results suggest that this class of compound represents a new possibility for developing drug candidates against acute leukemia.