6-(3-nitrophenyl)imidazo[2,1-b]thiazole

• 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)imidazo[2,1-b]thiazole
• 英文别名: 6-(3-Nitrophenyl)imidazo[2,1-b][1,3]thiazole
• 化学式: C₁₁H₇N₃O₂S
• mdl: MFCD00444821
• 分子量: 245.261
• InChiKey: APHADAMGMADIPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  91.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(3-nitrophenyl)imidazo[2,1-b]thiazole 在 oxone||potassium monopersulfate triple salt 、 palladium diacetate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 甲醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 4-fluoro-N-(3-((4-(6-(3-nitrophenyl)imidazo[2,1-b]thiazol-5-yl)pyrimidin-2-yl)amino)propyl)benzenesulfonamide
  参考文献：
  名称：

  Structural optimization of imidazothiazole derivatives affords a new promising series as B-Raf V600E inhibitors; synthesis, in vitro assay and in silico screening

  摘要：

  BRAF mutation is commonly known in a number of human cancer types. It is counted as a potential component in treating cancer. In this study, based on structural optimization of previously reported inhibitors (3-fluro substituted derivatives of imidazo[2,1-b]thiazole-based scaffold), we designed and synthesized sixteen new imidazo[2,1-b]thiazole derivatives with m-nitrophenyl group at position 6. The electron withdrawing properties was reserved while the polarity was modified compared to previously synthesized compounds (-F). Furthermore, the new substituted group (-NO2) provided an additional H-bond acceptor(s) which may bind with the target enzyme through additional interaction(s). In vitro cytotoxicity evaluation was performed against human cancer cell line (A375). In addition, in vitro enzyme assay was performed against mutated B-Raf (B-Raf V600E). Compounds 13a, 13g and 13f showed highest activity on mutated B-Raf with IC50 0.021, 0.035 and 0.020 µM. All target compounds were tested for in vitro cytotoxicity against NCI 60 cell lines. Compounds 13a and 13g were selected for 5 doses test mode. Moreover, in silico molecular simulation was explored in order to explore the possible interactions between the designed compounds and the B-Raf V600E active site.

  DOI：

  10.1016/j.bioorg.2020.103967
• 作为产物：
  描述：

  间硝基苯乙酮 以 乙醇 、 乙腈 为溶剂， 生成 6-(3-nitrophenyl)imidazo[2,1-b]thiazole
  参考文献：
  名称：

  桥头杂环合成中的高价碘：使用[羟基（甲苯磺酰氧基）碘]苯合成 6-芳基咪唑并[2,1-b]噻唑的简便途径

  摘要：

  摘要 α-甲苯磺酰氧基酮 (2)，通过使用乙腈中的 [羟基（甲苯磺酰氧基）碘] 苯 (HTIB) 对烯醇化酮 (1) 进行高价碘氧化很容易获得，专门生成 6-芳基咪唑并 [2,1-b] 噻唑（ 4) 用市售的 2-氨基噻唑 (3) 处理。

  DOI：

  10.1080/00397910500464863

文献信息

• [EN] IMIDAZO-THIAZOLE DERIVATIVES AS PROTEIN KINASE INHIBITORS<br/>[FR] DÉRIVÉS D'IMIDO-THIAZOLE EN TANT QU'INHIBITEURS DE PROTÉINES KINASES
  申请人：ABBOTT LAB

  公开号：WO2009070516A1

  公开（公告）日：2009-06-04

  Compounds of formula I that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed. Formula I and therapeutically acceptable salts, prodrugs and salts of prodrugs thereof, wherein X is CH or N; A1 is R1, OR1. NHR1, N(R1)2, NHC(O)R1, NHC(O)NHR1, NHC(O)N(R1)2, NHC(O)OR1, C(O)NHR1, C(O)N(R1)2, C=NOR1, or C(NH2)NOC(O)R1;

  公开了抑制蛋白激酶的化合物I的公式，包含这些化合物的组合物以及使用这些化合物治疗疾病的方法。公式I及其治疗上可接受的盐，前药和前药的盐，其中X为CH或N；A1为R1，OR1，NHR1，N(R1)2，NHC(O)R1，NHC(O)NHR1，NHC(O)N(R1)2，NHC(O)OR1，C(O)NHR1，C(O)N(R1)2，C=NOR1或C(NH2)NOC(O)R1。
• Modification of imidazothiazole derivatives gives promising activity in B-Raf kinase enzyme inhibition; synthesis, in vitro studies and molecular docking
  作者：Usama M. Ammar、Mohammed S. Abdel-Maksoud、Karim I. Mersal、Eslam M.H. Ali、Kyung Ho Yoo、Hong Seok Choi、Jae Kyun Lee、Sun Young Cha、Chang-Hyun Oh

  DOI：10.1016/j.bmcl.2020.127478

  日期：2020.10

  Based on structural features of dabrafenib (potent FDA approved B-Raf inhibitor), the design of new NH2-based imidazothiazole derivatives was carried out affording new highly potent derivatives of imidazothiazole-based scaffold with amino substitution on the terminal phenyl ring as well as side chain with sulfonamide group and terminal substituted phenyl ring. In vitro enzyme assay was investigated against

  B-Raf突变被确定为癌症治疗的主要靶标。根据dabrafenib（经FDA批准的强效B-Raf抑制剂）的结构特征，进行了新的基于NH 2的咪唑并噻唑衍生物的设计，从而提供了在末端苯环上具有氨基取代基的新的高效的咪唑并噻唑基支架衍生物。带有磺酰胺基的侧链和末端取代的苯环。研究了针对V600E B-Raf激酶的体外酶分析。化合物10l，10n和10o表现出更高的抑制活性（IC 50分别为1.20、4.31和6.21 nM）。体外针对NCI-60细胞系评估细胞毒性。大多数测试的衍生物显示出针对黑素瘤细胞系的细胞毒活性。化合物10k表现出最强的活性（IC 50 = 2.68 µM）。分子对接研究表明，新设计的衍生物保留了具有V600E B-Raf活性位点的达拉非尼相同的结合模式。研究表明，合成衍生物中的新修饰（被NH 2取代）对V600E B-Raf具有明显的抑制活性。该核心支架被认为是进一步优化结构和分子的关键化合物。
• IMIDAZOOXAZOLE DERIVATIVE HAVING ANTITUMOR EFFECT, AND PHARMACEUTICAL COMPOSITION INCLUDING SAME
  申请人：Korea Institute of Science and Technology

  公开号：EP3845539A1

  公开（公告）日：2021-07-07

  Provided is a pharmaceutical composition for use in preventing and treating tumors, the pharmaceutical composition including an imidazooxazole derivative compound, a solvate, a stereoisomer, or a pharmaceutically acceptable salt thereof as an active ingredient. The pharmaceutical composition is administered to an entity which has developed a tumor or is in danger of developing a tumor, and thus tumors can be prevented or treated.

  本发明提供了一种用于预防和治疗肿瘤的药物组合物，该药物组合物包括作为活性成分的咪唑恶唑衍生物化合物、其溶物、立体异构体或其药学上可接受的盐。该药物组合物用于已患肿瘤或有患肿瘤危险的实体，从而可预防或治疗肿瘤。
• Imidazooxazole derivative having antitumor effect, and pharmaceutical composition including same
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US11332479B2

  公开（公告）日：2022-05-17

  Provided is a pharmaceutical composition for preventing and treating tumors, the pharmaceutical composition including an imidazooxazole derivative compound, a solvate, a stereoisomer, or a pharmaceutically acceptable salt thereof as an active ingredient. The pharmaceutical composition is administered to an entity which has developed a tumor or is in danger of developing a tumor, and thus tumors can be prevented or treated.

  本发明提供了一种用于预防和治疗肿瘤的药物组合物，该药物组合物包括作为活性成分的咪唑恶唑衍生物化合物、其溶物、立体异构体或其药学上可接受的盐。该药物组合物可用于已罹患肿瘤或有罹患肿瘤危险的实体，从而预防或治疗肿瘤。
• Acylthiourea, Acylurea, and Acylguanidine Derivatives with Potent Hedgehog Inhibiting Activity
  作者：Antonio Solinas、Hélène Faure、Hermine Roudaut、Elisabeth Traiffort、Angèle Schoenfelder、André Mann、Fabrizio Manetti、Maurizio Taddei、Martial Ruat

  DOI：10.1021/jm2013369

  日期：2012.2.23

  The Smoothened (Smo) receptor is the major transducer of the Hedgehog (Hh) signaling pathway. On the basis of the structure of the acylthiourea Smo antagonist (MRT-10), a number of different series of analogous compounds were prepared by ligand-based structural optimization. The acylthioureas, originally identified as actives, were converted into the corresponding acylureas or acylguanidines. In each series, similar structural trends delivered potent compounds with IC50 values in the nanomolar range with respect to the inhibition of the Hh signaling pathway in various cell-based assays and of BODIPY-cyclopamine binding to human Smo. The similarity of their biological activities, in spite of discrete structural differences, may reveal the existence of hydrogen-bonding interactions between the ligands and the receptor pocket. Biological potency of compounds 61, 72, and 86 (MRT-83) were comparable to those of the clinical candidate GDC-0449. These findings suggest that these original molecules will help delineate Smo and Hh functions and can be developed as potential anticancer agents.