6-(3-nitrophenyl)imidazole and [2,1-b]thiazole-3-ethyl formate | 1131608-22-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-(3-nitrophenyl)imidazole and [2,1-b]thiazole-3-ethyl formate
• 英文别名: Ethyl 6-(3-nitrophenyl)imidazo[2,1-b][1,3]thiazole-3-carboxylate；ethyl 6-(3-nitrophenyl)imidazo[2,1-b][1,3]thiazole-3-carboxylate
• CAS: 1131608-22-4
• 化学式: C₁₄H₁₁N₃O₄S
• 分子量: 317.325
• InChiKey: GHCHKFSPMOWPSI-UHFFFAOYSA-N

物化性质

• 密度：
  1.50±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  118
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(3-nitrophenyl)imidazole and [2,1-b]thiazole-3-ethyl formate 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 56.0h， 生成 tert-butyl 4-((6-(3-nitrophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Search for a novel SIRT1 activator: Structural modification of SRT1720 and biological evaluation

  摘要：

  Syntheses and biological evaluation of novel SRT1720 derivatives are described in search for new candidates of SIRT1 activator. Several parts of the SRT1720 structure, including piperazine moiety, quinoxaline ring on the amide group, and position of the amide function, were modified, and the assay results indicated that transfer of the ortho amide-substituent regarding to the imidazo[1,2-b]thiazole core onto the meta position resulted in improvement of SIRT1 activation ability. Modeling analyses of SRT1720 and the most potent derivative bound to model complex of SIRT1 with peptide substrate were also performed. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.070
• 作为产物：
  描述：

  2-氨基噻唑-4-甲酸乙酯 、 2-溴-3'-硝基苯乙酮 以 1,4-二氧六环 为溶剂， 反应 12.0h， 生成 6-(3-nitrophenyl)imidazole and [2,1-b]thiazole-3-ethyl formate
  参考文献：
  名称：

  Discovery of 6-phenylimidazo[2,1-b]thiazole derivatives as a new type of FLT3 inhibitors

  摘要：

  In this investigation, a series of 6-phenylimidazo[2,1-b] thiazole derivatives were synthesized. Structure-activity relationship (SAR) analysis of these compounds based on cellular assays led to the discovery of a number of compounds that showed potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell line MV4-11, but very weak or no activity against FLT3-independent human cervical cancer cell line Hela. FLT3 kinase inhibition assays were then performed on the three most active compounds. Among these compounds, 6-(4-(3-(5-(tert-butyl)isoxazol- 3-yl)ureido)phenyl)-N-(3-(dimethylamino)propyl)imidazo[2,1-b]thiazole-3-carboxamide (19) exhibited the highest potency in both cellular (MV4-11, IC50: 0.002 mu M) and enzymatic (FLT3, IC50: 0.022 mu M) assays. Further in-depth in vitro anti-AML activity and mechanism of action studies were carried out on compound 19. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.08.068

文献信息

• 10.1039/d4ra00557k
  作者：Lin, Hai-Feng、Jiang, Yu-Cai、Chen, Zhi-Wei、Zheng, Lin-Lin

  DOI：10.1039/d4ra00557k

  日期：——

  pharmacological activity and minimize side effects. The combination of an indole ring and imidazole[2,1-b]thiazole has shown promising potential as a group that exhibits potent anti-inflammatory effects. In this study, we designed and synthesized a series of derivatives comprising indole-2-formamide benzimidazole[2,1-b]thiazole to evaluate their impact on LPS-induced production of pro-inflammatory cytokines NO, IL-6

  分子杂交是药物化学中广泛采用的药物修饰技术，旨在增强药理活性并最大限度地减少副作用。吲哚环和咪唑[2,1-b]噻唑的组合作为具有有效抗炎作用的基团显示出巨大的潜力。在本研究中，我们设计并合成了一系列包含吲哚-2-甲酰胺苯并咪唑[2,1-b]噻唑的衍生物，以评估它们对 LPS 诱导的促炎细胞因子 NO、IL-6 和 TNF-α 产生的影响。 α 释放以及 RAW264.7 细胞中的铁死亡。研究结果表明，大多数化合物能有效抑制 LPS 诱导的 RAW264.7 细胞中促炎细胞因子 NO、IL-6 和 TNF-α 的释放。在测试的化合物中，化合物13b表现出最有效的抗炎活性。细胞毒性测定结果表明化合物13b无毒。此外，化合物 13b 被发现可以提高 ROS、MDA 和 Fe2+ 的水平，同时降低 GSH 含量，从而促进铁死亡过程。因此，化合物 13b 显示出作为抗炎药物未来开发的前景。
• Search for a novel SIRT1 activator: Structural modification of SRT1720 and biological evaluation
  作者：Yuji Matsuya、Yuta Kobayashi、Sayumi Uchida、Yukihiro Itoh、Hideyuki Sawada、Takayoshi Suzuki、Naoki Miyata、Kenji Sugimoto、Naoki Toyooka

  DOI：10.1016/j.bmcl.2013.06.070

  日期：2013.9

  Syntheses and biological evaluation of novel SRT1720 derivatives are described in search for new candidates of SIRT1 activator. Several parts of the SRT1720 structure, including piperazine moiety, quinoxaline ring on the amide group, and position of the amide function, were modified, and the assay results indicated that transfer of the ortho amide-substituent regarding to the imidazo[1,2-b]thiazole core onto the meta position resulted in improvement of SIRT1 activation ability. Modeling analyses of SRT1720 and the most potent derivative bound to model complex of SIRT1 with peptide substrate were also performed. (C) 2013 Elsevier Ltd. All rights reserved.
• Discovery of 6-phenylimidazo[2,1-b]thiazole derivatives as a new type of FLT3 inhibitors
  作者：Xing-Dong Lin、Hui-Wen Yang、Shuang Ma、Wei-Wei Li、Chun-Hui Zhang、Wen-Jing Wang、Rong Xiang、Lin-Li Li、Sheng-Yong Yang

  DOI：10.1016/j.bmcl.2015.08.068

  日期：2015.10

  In this investigation, a series of 6-phenylimidazo[2,1-b] thiazole derivatives were synthesized. Structure-activity relationship (SAR) analysis of these compounds based on cellular assays led to the discovery of a number of compounds that showed potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell line MV4-11, but very weak or no activity against FLT3-independent human cervical cancer cell line Hela. FLT3 kinase inhibition assays were then performed on the three most active compounds. Among these compounds, 6-(4-(3-(5-(tert-butyl)isoxazol- 3-yl)ureido)phenyl)-N-(3-(dimethylamino)propyl)imidazo[2,1-b]thiazole-3-carboxamide (19) exhibited the highest potency in both cellular (MV4-11, IC50: 0.002 mu M) and enzymatic (FLT3, IC50: 0.022 mu M) assays. Further in-depth in vitro anti-AML activity and mechanism of action studies were carried out on compound 19. (C) 2015 Elsevier Ltd. All rights reserved.