1-(4-(4-chlorophenyl)thiazol-2-yl)-2-(1-(pyridin-2-yl)ethylidene)hydrazine | 957754-14-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-(4-chlorophenyl)thiazol-2-yl)-2-(1-(pyridin-2-yl)ethylidene)hydrazine
• 英文别名: (2-(1-(pyridin-2-yl)ethylene)hydrazinyl)-4-(4-chlorophenyl)-1,3-thiazole；4-(4-chlorophenyl)-N-(1-pyridin-2-ylethylideneamino)-1,3-thiazol-2-amine
• CAS: 957754-14-2
• 化学式: C₁₆H₁₃ClN₄S
• 分子量: 328.825
• InChiKey: BURSBQLPMYQBJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-乙酰基吡啶 在 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 0.28h， 生成 1-(4-(4-chlorophenyl)thiazol-2-yl)-2-(1-(pyridin-2-yl)ethylidene)hydrazine
  参考文献：
  名称：

  评价作为组蛋白乙酰转移酶抑制剂的（噻唑-2-基））酮和类似物的大型文库：酶和细胞研究

  摘要：

  最近，我们描述了一些（噻唑-2-基）azo作为抗原生动物，抗真菌和抗MAO试剂以及Gcn5 HAT抑制剂。在这些最后的化合物中，CPTH2和CPTH6在细胞中显示出HAT抑制作用和广泛的抗癌特性。为了鉴定比两个原型更有效的HAT抑制剂，我们合成了几种新的（噻唑-2-基）azo酮，包括一些相关的噻唑烷和嘧啶4（3 H）-酮，并测试了我们现有的整个文库针对人p300和PCAF HAT酶的实验室。某些化合物（1x，1c '，1d '，1i '和2m）在抑制p300 HAT酶方面比CPTH2和CPTH6更有效。在人白血病U937和结肠癌HCT116细胞（100μM，30小时）中进行测试时，1x，1i '和2m产生的凋亡（U937细胞）或类似细胞（HCT116细胞）高于CPTH6，并且在诱导细胞分化方面比CPTH6更有效（U937细胞）。

  DOI：

  10.1016/j.ejmech.2014.04.042

文献信息

• (Thiazol-2-yl)hydrazone derivatives from acetylpyridines as dual inhibitors of MAO and AChE: synthesis, biological evaluation and molecular modeling studies
  作者：Melissa D’Ascenzio、Paola Chimenti、Maria Concetta Gidaro、Celeste De Monte、Daniela De Vita、Arianna Granese、Luigi Scipione、Roberto Di Santo、Giosuè Costa、Stefano Alcaro、Matilde Yáñez、Simone Carradori

  DOI：10.3109/14756366.2014.987138

  日期：2015.11.2

  Several (thiazol-2-yl)hydrazone derivatives from 2-, 3- and 4-acetylpyridine were synthesized and tested against human monoamine oxidase (hMAO) A and B enzymes. Most of them had an inhibitory effect in the low micromolar/high nanomolar range, being derivatives of 4-acetylpyridine selective hMAO-B inhibitors also at low nanomolar concentrations. The structure-activity relationship, as confirmed by molecular

  合成了2-，3-和4-乙酰基吡啶的几种（噻唑-2-基）hydr衍生物，并针对人单胺氧化酶（hMAO）A和B酶进行了测试。它们中的大多数在低微摩尔/高纳摩尔范围内具有抑制作用，它们也是在低纳摩尔浓度下的4-乙酰基吡啶选择性hMAO-B抑制剂的衍生物。通过分子建模研究证实的结构活性关系证明，连接至肼基氮原子的吡啶环和噻唑C4处的取代芳基部分赋予了对hMAO酶的抑制作用。随后，测试了最强的hMAO-B抑制剂对乙酰胆碱酯酶（AChE）的作用，最有趣的化合物显示出在低微摩尔范围内的活性。
• Synthesis of a novel series of thiazole-based histone acetyltransferase inhibitors
  作者：Daniela Secci、Simone Carradori、Bruna Bizzarri、Adriana Bolasco、Paola Ballario、Zoi Patramani、Paola Fragapane、Stefano Vernarecci、Claudia Canzonetta、Patrizia Filetici

  DOI：10.1016/j.bmc.2014.01.022

  日期：2014.3

  Acetylation, which targets a broad range of histone and non-histone proteins, is a reversible mechanism and plays a critical role in eukaryotic genes activation/deactivation. Acetyltransferases are very well conserved through evolution. This allows the use of a simple model organism, such as budding yeast, for the study of their related processes and to discover specific inhibitors. Following a simple yeast-based chemogenetic approach, we have identified a novel HAT (histone acetyltransferase) inhibitor active both in vitro and in vivo. This new synthetic compound,1-(4-(4-chlorophenyl)thiazol-2-yl)-2-(propan-2-ylidene) hydrazine, named BF1, showed substrate selectivity for histone H3 acetylation and inhibitory activity in vitro on recombinant HAT Gcn5 and p300. Finally, we tested BF1 on human cells, HeLa as control and two aggressive cancer cell lines: a neuroblastoma from neuronal tissue and glioblastoma from brain tumour. Both global acetylation of histone H3 and specific acetylation at lysine 18 (H3AcK18) were lowered by BF1 treatment. Collectively, our results show the efficacy of this novel HAT inhibitor and propose the utilization of BF1 as a new, promising tool for future pharmacological studies. (C) 2014 Elsevier Ltd. All rights reserved.