6-bromo-2-iodobenzo[d]thiazole | 1188077-72-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 6-bromo-2-iodobenzo[d]thiazole
• 英文别名: 6-bromo-2-iodo-1,3-benzothiazole
• CAS: 1188077-72-6
• 化学式: C₇H₃BrINS
• 分子量: 339.982
• InChiKey: BKEJBIDIIKBSFD-UHFFFAOYSA-N

物化性质

• 沸点：
  374.9±34.0 °C(Predicted)
• 密度：
  2.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2934200090

反应信息

• 作为反应物：
  描述：

  6-bromo-2-iodobenzo[d]thiazole 、 5-溴-N-(叔丁氧羰基)吲哚2-硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 2.0h， 生成 6-bromo-2-(5-bromo-1H-indol-2-yl)benzo[d] thaizole
  参考文献：
  名称：

  Discovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus aureus infections

  摘要：

  A novel series of bis-indoles derived from naturally occurring marine alkaloid 4 were synthesized and evaluated as inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK). PK is not only critical for bacterial survival which would make it a target for development of novel antibiotics, but it is reported to be one of the most highly connected 'hub proteins' in MRSA, and thus should be very sensitive to mutations and making it difficult for the bacteria to develop resistance. From the co-crystal structure of cis-3-4-dihydrohamacanthin B (4) bound to S. aureus PK we were able to identify the pharmacophore needed for activity. Consequently, we prepared simple direct linked bis-indoles such as 10b that have similar anti-MRSA activity as compound 4. Structure-activity relationship (SAR) studies were carried out on 10b and led us to discover more potent compounds such as 10c, 10d, 10k and 10m with enzyme inhibiting activities in the low nanomolar range that effectively inhibited the bacteria growth in culture with minimum inhibitory concentrations (MIC) for MRSA as low as 0.5 mu g/ml. Some potent PK inhibitors, such as 10b, exhibited attenuated antibacterial activity and were found to be substrates for an efflux mechanism in S. aureus. Studies comparing a wild type S. aureus with a construct (S. aureus LAC Delta pyk::ErmR) that lacks PK activity confirmed that bactericidal activity of 10d was PK-dependant. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.020
• 作为产物：
  描述：

  2-氨基-6-溴苯并噻唑 在 N-碘代丁二酰亚胺 、 sodium nitrite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以27 %的产率得到6-bromo-2-iodobenzo[d]thiazole
  参考文献：
  名称：

  Copper‐Catalyzed Aryne Insertion into the Carbon‐Iodine Bond of Heteroaryl Iodides

  摘要：

  摘要 首次实现了在杂芳基碘化物的碳-碘键中插入丙烯。这一新型反应为从杂芳基碘化物和邻硅芳基三酸酯合成有价值的 2-iodoheterobiaryls 构建模块提供了一条高效途径，且具有极佳的区域选择性。铜（I）催化剂带有 N-杂环碳烯（NHC）配体，对完成反应至关重要。对照反应和 DFT 计算表明，作为路易斯酸的铜与杂芳基碘化物的氮原子配位介导了芳基插入杂芳基碳-碘键。

  DOI：

  10.1002/anie.202305146

文献信息

• [EN] DERIVATIVES OF HETEROARYLSULFONAMIDES, THEIR PREPARATION AND THEIR APPLICATION IN HUMAN THERAPY<br/>[FR] DÉRIVÉS D'HÉTÉROARYLSULFONAMIDES, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPIE HUMAINE
  申请人：PF MEDICAMENT

  公开号：WO2012069503A1

  公开（公告）日：2012-05-31

  The present invention concerns derivatives of heteroarylsulfonamides, notably as blockers of Kv potassium channels, and more particularly of channels Kv1.5, Kv4.3 or Kv11.1, their application in clinical therapy and their preparation methods. These compounds correspond to the following general formula (I): where R1 represents one or more substituents of the phenyl core X such as: hydrogen, halogen, trifluoromethyl, trifluoromethoxy, linear or branched C1-C4 alkyl, or linear or branched C1-C4 alkoxy, A represents oxygen or sulphur, B represents nitrogen when n=1 or 2 and D represents −C(=O)-, or B represents CH when n=0 and D represents −CH2O− or when n=1 and D represents −O−, R2 represents a hydrogen, a methyl, a fluorine or chlorine atom or a methoxy, HetAr represents a pyridyl or quinolyl group, possibly substituted by a group such as a linear or branched C1-C4 alkyl, a linear or branched C1-C4 alkoxy, a halogen, or a trifluoromethyl, and to their pharmaceutically acceptable salts.

  本发明涉及杂环磺酰胺衍生物，特别是作为Kv钾通道的阻滞剂，更具体地是Kv1.5、Kv4.3或Kv11.1通道的阻滞剂，它们在临床治疗中的应用以及它们的制备方法。这些化合物对应于以下一般式（I）：其中R1代表苯环X的一个或多个取代基，如：氢、卤素、三氟甲基、三氟甲氧基、直链或支链C1-C4烷基，或直链或支链C1-C4烷氧基，A代表氧或硫，当n=1或2时，B代表氮，D代表−C(=O)-；当n=0时，B代表CH，D代表−CH2O−；当n=1时，B代表CH，D代表−O−，R2代表氢、甲基、氟或氯原子或甲氧基，HetAr代表可能被直链或支链C1-C4烷基、直链或支链C1-C4烷氧基、卤素或三氟甲基等取代的吡啶基或喹啉基，以及它们的药用可接受盐。
• Activation of perfluoroalkyl iodides by anions: extending the scope of halogen bond activation to C(sp³)–H amidation, C(sp²)–H iodination, and perfluoroalkylation reactions
  作者：Yaxin Wang、Zehui Cao、Qin He、Xin Huang、Jiaxi Liu、Helfried Neumann、Gong Chen、Matthias Beller

  DOI：10.1039/d2sc06145g

  日期：——

  A simple, efficient, and convenient activation of perfluoroalkyl iodides by tBuONa or KOH, without expensive photo- or transition metal catalysts, allows the promotion of versatile α-sp3 C–H amidation reactions of alkyl ethers and benzylic hydrocarbons, C–H iodination of heteroaryl compounds, and perfluoroalkylations of electron-rich π bonds. Mechanistic studies show that these novel protocols are

  在没有昂贵的光催化剂或过渡金属催化剂的情况下，通过t BuONa 或 KOH对全氟烷基碘进行简单、高效和方便的活化，可以促进烷基醚和苄基烃、C-H 的通用 α-sp 3 C-H 酰胺化反应杂芳基化合物的碘化，以及富电子π键的全氟烷基化。机理研究表明，这些新方案基于全氟烷基碘与t BuONa 或 KOH 之间的卤素键相互作用，可促进全氟烷基碘在温和条件下均裂。
• Discovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus aureus infections
  作者：Nag S. Kumar、Edie M. Dullaghan、B. Brett Finlay、Huansheng Gong、Neil E. Reiner、J. Jon Paul Selvam、Lisa M. Thorson、Sara Campbell、Nicholas Vitko、Anthony R. Richardson、Roya Zoraghi、Robert N. Young

  DOI：10.1016/j.bmc.2014.01.020

  日期：2014.3

  A novel series of bis-indoles derived from naturally occurring marine alkaloid 4 were synthesized and evaluated as inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK). PK is not only critical for bacterial survival which would make it a target for development of novel antibiotics, but it is reported to be one of the most highly connected 'hub proteins' in MRSA, and thus should be very sensitive to mutations and making it difficult for the bacteria to develop resistance. From the co-crystal structure of cis-3-4-dihydrohamacanthin B (4) bound to S. aureus PK we were able to identify the pharmacophore needed for activity. Consequently, we prepared simple direct linked bis-indoles such as 10b that have similar anti-MRSA activity as compound 4. Structure-activity relationship (SAR) studies were carried out on 10b and led us to discover more potent compounds such as 10c, 10d, 10k and 10m with enzyme inhibiting activities in the low nanomolar range that effectively inhibited the bacteria growth in culture with minimum inhibitory concentrations (MIC) for MRSA as low as 0.5 mu g/ml. Some potent PK inhibitors, such as 10b, exhibited attenuated antibacterial activity and were found to be substrates for an efflux mechanism in S. aureus. Studies comparing a wild type S. aureus with a construct (S. aureus LAC Delta pyk::ErmR) that lacks PK activity confirmed that bactericidal activity of 10d was PK-dependant. (C) 2014 Elsevier Ltd. All rights reserved.
• Copper‐Catalyzed Aryne Insertion into the Carbon‐Iodine Bond of Heteroaryl Iodides
  作者：Wen‐Xuan Cao、Lei Zhu、Yiyi He、Run Wang、Ming Liu、Qin Ouyang、Qing Xiao

  DOI：10.1002/anie.202305146

  日期：2023.9.25

  Aryne insertions into the carbon‐iodine bond of heteroaryl iodides has been achieved for the first time. This novel reaction provides an efficient pathway for the synthesis of valuable building blocks 2‐iodoheterobiaryls from heteroaryl iodides and o‐silylaryl triflates in excellent regioselectivity. The copper(I) catalyst, which bears a N‐heterocyclic carbene (NHC) ligand, is essential to accomplish the reaction. Control reactions and DFT calculations indicate that the coordination of copper, as a Lewis acid, with nitrogen atoms of heteroaryl iodides mediates the insertion of arynes into heteroaryl carbon‐iodine bonds.

  摘要 首次实现了在杂芳基碘化物的碳-碘键中插入丙烯。这一新型反应为从杂芳基碘化物和邻硅芳基三酸酯合成有价值的 2-iodoheterobiaryls 构建模块提供了一条高效途径，且具有极佳的区域选择性。铜（I）催化剂带有 N-杂环碳烯（NHC）配体，对完成反应至关重要。对照反应和 DFT 计算表明，作为路易斯酸的铜与杂芳基碘化物的氮原子配位介导了芳基插入杂芳基碳-碘键。