6-(3-methoxyphenyl)-5-(2-(methylthio)pyrimidin-4-yl)imidazo[2,1-b]thiazole | 815596-13-5

• 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-methoxyphenyl)-5-(2-(methylthio)pyrimidin-4-yl)imidazo[2,1-b]thiazole
• 英文别名: 6-(3-Methoxyphenyl)-5-(2-methylsulfanylpyrimidin-4-yl)imidazo[2,1-b][1,3]thiazole
• CAS: 815596-13-5
• 化学式: C₁₇H₁₄N₄OS₂
• 分子量: 354.456
• InChiKey: DRQPTAMKMYCCNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  106
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(3-methoxyphenyl)-5-(2-(methylthio)pyrimidin-4-yl)imidazo[2,1-b]thiazole 在 Oxone 、 三溴化硼 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 25.5h， 生成 N-(2-(4-(6-(3-hydroxyphenyl)imidazo[2,1-b]thiazol-5-yl)pyrimidin-2-ylamino)ethyl)-2-hydroxybenzamide
  参考文献：
  名称：

  New imidazo[2,1-b]thiazole derivatives: Synthesis, in vitro anticancer evaluation, and in silico studies

  摘要：

  A series of 18 new imidazo[2,1-b]thiazole derivatives was synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-60 cell line panel were tested. Compounds 15, 16, 18, 22, 26-28, and 31 showed superior potency against A375P to sorafenib. In addition, compounds 26 and 27 showed selectivity toward melanoma cell lines than for other cancer types. Both compounds exerted sub-micromolar IC50 values over 7 (including A375P) and 6 melanoma cell lines, respectively. in silico studies are also reported. ADME profiling, in silico toxicity, drug-likeness, and drug-score data of compounds 26 and 27 are promising. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.024
• 作为产物：
  描述：

  6-(3-methoxyphenyl)imidazo[2,1-b]thiazole 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 溴 、 potassium acetate 、 caesium carbonate 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 49.0h， 生成 6-(3-methoxyphenyl)-5-(2-(methylthio)pyrimidin-4-yl)imidazo[2,1-b]thiazole
  参考文献：
  名称：

  发现新型咪唑并[2,1- b ]噻唑衍生物作为有力的体外和体内抗黑素瘤活性的有效泛RAF抑制剂

  摘要：

  BRAF是MAPK级联反应的重要组成部分。BRAF，特别是V600E的突变会导致MAPK途径过度活化和细胞生长不受控制。对突变的BRAF的选择性抑制剂的抗性是治疗许多癌症类型的主要障碍。在这项工作中，合成了一系列具有末端磺酰胺部分的新的（咪唑并[2,1 - b ]噻唑-5-基）嘧啶衍生物。研究了新系列的Pan-RAF抑制作用，并讨论了结构-活性关系。测试了目标化合物对NCI-60细胞系的抗增殖活性。对最具活性的化合物进行了进一步测试，以获得针对癌细胞的IC 50值。化合物27c末端开链磺酰胺和带有环状磺酰胺部分的38a在酶法和细胞分析中显示出最高的活性，并且两种化合物都能够抑制MEK和ERK的磷酸化。选择化合物38a以测试其针对黑素瘤的体内活性。报告了细胞和动物活动。

  DOI：

  10.1021/acs.jmedchem.1c00230

文献信息

• Discovery of first-in-class imidazothiazole-based potent and selective ErbB4 (HER4) kinase inhibitors
  作者：Seyed-Omar Zaraei、Rawan M. Sbenati、Nour N. Alach、Hanan S. Anbar、Randa El-Gamal、Hamadeh Tarazi、Mahmoud K. Shehata、Mohammed S. Abdel-Maksoud、Chang-Hyun Oh、Mohammed I. El-Gamal

  DOI：10.1016/j.ejmech.2021.113674

  日期：2021.11

  derivatives as first-in-class potent and selective ErbB4 (HER4) inhibitors. There are no other reported selective inhibitors of this kinase in the literature, that's why they are considered as first-in-class. In addition, none of the reported non-selective ErbB4 inhibitors possesses imidazothiazole nucleus in its structure. Therefore, there is novelty in this work in both kinase selectivity and chemical

  本文报道了新型咪唑并噻唑衍生物作为一流的强效选择性 ErbB4 (HER4) 抑制剂。文献中没有其他报道的这种激酶的选择性抑制剂，这就是为什么它们被认为是一流的。此外，报道的非选择性 ErbB4 抑制剂中没有一个在其结构中具有咪唑并噻唑核。因此，这项工作在激酶选择性和化学结构方面都具有新颖性。化合物Ik和IIa是最有效的 ErbB4 激酶抑制剂（IC 50 分别 为 15.24 和 17.70 nM）。化合物Ik显示出有希望的抗增殖活性。与正常细胞相比，它对癌细胞系具有选择性。其穿透T-47D细胞膜并抑制细胞内ErbB4激酶的能力已得到证实。此外，化合物Ik和IIa都具有额外的优点，例如对 HERG 离子通道和 CYP 3A4 和 2D6 的效力较弱。进行了分子对接和动态模拟研究以解释结合相互作用。
• Inhibitors of P38 and Methods of Using the Same
  申请人：Ashwell A. Mark

  公开号：US20070270418A1

  公开（公告）日：2007-11-22

  In general, the present invention relates to compounds capable of inhibiting p38, methods for inhibiting p38 in vivo or in vitro, and methods for treating conditions associated with p38 activity or cytokine activity.

  一般而言，本发明涉及能够抑制p38的化合物，抑制p38在体内或体外的方法，以及治疗与p38活性或细胞因子活性相关的疾病的方法。
• IMIDAZOTHIAZOLES AS P38-KINASE-INHIBITORS
  申请人：ARQULE, INC.

  公开号：EP2251343A1

  公开（公告）日：2010-11-17

  In general, the present invention relates to compounds capable of inhibiting p38, methods for inhibiting p38 in vivo or in vitro, and methods for treating conditions associated with p38 activity or cytokine activity.

  总的来说，本发明涉及能够抑制 p38 的化合物、体内或体外抑制 p38 的方法，以及治疗与 p38 活性或细胞因子活性相关的疾病的方法。
• Imidazothiazole-based potent inhibitors of V600E-B-RAF kinase with promising anti-melanoma activity: biological and computational studies
  作者：Hanan S. Anbar、Mohammed I. El-Gamal、Hamadeh Tarazi、Bong S. Lee、Hong R. Jeon、Dow Kwon、Chang-Hyun Oh

  DOI：10.1080/14756366.2020.1819260

  日期：2020.1.1

  A series of imidazothiazole derivatives possessing potential activity against melanoma cells were investigated for molecular mechanism of action. The target compounds were tested against V600E-B-RAF and RAF1 kinases. Compound1zbis the most potent against both kinases with IC(50)values 0.978 and 8.2 nM, respectively. It showed relative selectivity against V600E mutant B-RAF kinase. Compound1zbwas also tested against four melanoma cell lines and exerted superior potency (IC(50)0.18-0.59 mu M) compared to the reference standard drug, sorafenib (IC(50)1.95-5.45 mu M). Compound1zbdemonstrated also prominent selectivity towards melanoma cells than normal skin cells. It was further tested in whole-cell kinase assay and showed in-cell V600E-B-RAF kinase inhibition with IC(50)of 0.19 mu M. Compound1zbinduces apoptosis not necrosis in the most sensitive melanoma cell line, UACC-62. Furthermore, molecular dynamic and 3D-QSAR studies were done to investigate the binding mode and understand the pharmacophoric features of this series of compounds.
• US7902192B2
  申请人：——

  公开号：US7902192B2

  公开（公告）日：2011-03-08