6-(3-methoxyphenyl)imidazo[2,1-b]thiazole | 92754-06-8

• 物质功能分类: 有机原料 - 杂环化合物
• 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)imidazo[2,1-b]thiazole
• 英文别名: 6-(3-methoxyphenyl)imidazo[2,1-b][1,3]thiazole
• CAS: 92754-06-8
• 化学式: C₁₂H₁₀N₂OS
• 分子量: 230.29
• InChiKey: JNGUEZACXQNHRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  54.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(3-methoxyphenyl)imidazo[2,1-b]thiazole 在 oxone||potassium monopersulfate triple salt 、 palladium diacetate 、 三溴化硼 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.5h， 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：

  Imidazothiazole-based potent inhibitors of V600E-B-RAF kinase with promising anti-melanoma activity: biological and computational studies

  摘要：

  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.

  DOI：

  10.1080/14756366.2020.1819260
• 作为产物：
  描述：

  2-溴-3‘-甲氧基苯乙酮 在 lithium aluminium tetrahydride 、 potassium tert-butylate 、 氧气 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 22.0h， 生成 6-(3-methoxyphenyl)imidazo[2,1-b]thiazole
  参考文献：
  名称：

  含杂芳基的伯醇和仲醇中的无金属好氧氧化选择性C–C键裂解。

  摘要：

  据报道，伯和仲杂芳基醇中无过渡金属的需氧氧化选择性C–C键断裂反应。该反应是高效的并且耐受各种杂芳基醇，产生羧酸衍生物和中性杂芳族化合物。实验研究与密度泛函理论计算相结合，揭示了选择性C–C键断裂的机理。该策略还提供了另一种简单的羧化反应方法。

  DOI：

  10.1021/acs.orglett.9b00563

文献信息

• Discovery of New Imidazo[2,1-<i>b</i>]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising <i>In Vitro</i> and <i>In Vivo</i> Anti-melanoma Activity
  作者：Mohammed S. Abdel-Maksoud、Mohammed I. El-Gamal、Bong S. Lee、Mahmoud M. Gamal El-Din、Hong R. Jeon、Dow Kwon、Usama M. Ammar、Karim I. Mersal、Eslam M. H. Ali、Kyung-Tae Lee、Kyung Ho Yoo、Dong Keun Han、Jae Kyun Lee、Garam Kim、Hong Seok Choi、Young Jik Kwon、Kwan Hyi Lee、Chang Hyun Oh

  DOI：10.1021/acs.jmedchem.1c00230

  日期：2021.5.27

  obstacle against treatment of many cancer types. In this work, a series of new (imidazo[2,1-b]thiazol-5-yl)pyrimidine derivatives possessing a terminal sulfonamide moiety were synthesized. Pan-RAF inhibitory effect of the new series was investigated, and structure–activity relationship is discussed. Antiproliferative activity of the target compounds was tested against the NCI-60 cell line panel. The

  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。
• 6-(Hydroxyphenyl)imidazo[2,1-b]thiazoles as Potential Antiinflammatory Agents: Effects on Human Neutrophil Functions
  作者：Aldo Andreani、Mirella Rambaldi、Alberto Leoni、Alessandra Locatelli、Rita Morigi、Serena Traniello、Alessio Cariani、Olivia Rizzuti、Susanna Spisani

  DOI：10.1135/cccc20000267

  日期：——

  Synthesis of 6-(hydroxyphenyl)imidazo[2,1-b]thiazoles related to levamisole from the corresponding methoxy derivatives is reported. These compounds were tested on in vitro neutrophil activation, namely locomotion induced by chemoattractants, superoxide generation and lysozyme degranulation triggered by agonists. These functions were evaluated after cell pulse with different concentrations of the drugs. Several derivatives showed significant inhibitory effects, in some cases more potent than the parent compound.

  报道了从相应的甲氧基衍生物合成与左旋咪唑相关的6-(羟基苯基)咪唑并[2,1-b]噻唑。这些化合物在体外中性粒细胞活化方面进行了测试，即由趋化剂诱导的运动、由激动剂引发的超氧化物生成和溶菌酶脱颗粒。这些功能在细胞脉冲后经不同浓度药物评估。一些衍生物显示出显著的抑制作用，在某些情况下比母化合物更强效。
• 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。
• RAF inhibitors and their uses
  申请人：Lapierre Jean-Marc

  公开号：US20070281955A1

  公开（公告）日：2007-12-06

  The present invention provides imidazooxazole and imidazothiazole compounds and their synthesis. The compounds of the present invention are capable of inhibiting the activity of RAF kinase, such as B-RAF V600E . The compounds are useful for the treatment of cell proliferative disorders such as cancer.

  本发明提供了咪唑氧唑和咪唑硫唑化合物及其合成方法。本发明的化合物能够抑制RAF激酶的活性，例如B-RAFV600E。这些化合物对于治疗细胞增殖性疾病，如癌症，具有有用的作用。
• Synthesis of imidazooxazole and imidazothiazole inhibitors of p38 map kinase
  申请人：Ashwell Mark A.

  公开号：US20090111985A1

  公开（公告）日：2009-04-30

  An efficient route for the synthesis is of formula (I) of imidazooxazole and imidazothiazole inhibitors of the p38 MAP kinase pathway, useful as therapeutics for disease conditions including inflammation and auto-immune responses is described.

  本文描述了一种有效的合成公式(I)的咪唑噁唑和咪唑硫唑抑制剂的路线，这些抑制剂可用作治疗炎症和自身免疫反应等疾病情况的药物。