8-(cyclohexyloxy)-1-oxo-2-phenyl-1H-pyrido[2,1-b][1,3]benzothiazole-4-carboxylic acid | 1355361-72-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 8-(cyclohexyloxy)-1-oxo-2-phenyl-1H-pyrido[2,1-b][1,3]benzothiazole-4-carboxylic acid
• 英文别名: 8-(Cyclohexoxy)-1-oxo-2-phenyl-pyrido[2,1-b][1,3]benzothiazole-4-carboxylic acid；8-cyclohexyloxy-1-oxo-2-phenylpyrido[2,1-b][1,3]benzothiazole-4-carboxylic acid
• CAS: 1355361-72-6
• 化学式: C₂₄H₂₁NO₄S
• 分子量: 419.501
• InChiKey: PWLKJKKKBOHGAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(cyclohexyloxy)-1-oxo-2-phenyl-1H-pyrido[2,1-b][1,3]benzothiazole-4-carboxylic acid 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 为溶剂， 反应 7.0h， 生成 3-({[8-(cyclohexyloxy)-1-oxo-2-phenyl-1H-pyrido[2,1-b][1,3]benzothiazol-4-yl]carbonyl}amino)butanoic acid
  参考文献：
  名称：

  可持续的三成分一锅法获得活性抗黄病毒制剂

  摘要：

  属于黄病毒属的蚊媒病毒，例如登革热病毒（DENV）和寨卡病毒（ZIKV），会引起人类感染，从轻度的流感样症状到出血热，肝炎和神经病。迄今为止，只有少数黄病毒的疫苗，而没有有效的治疗方法。 吡啶并苯并噻唑（PBTZ）衍生物是一类具有广阔前景的广谱抗黄病毒活性的化合物，据报道，其中大多数是黄病毒NS5聚合酶的有效抑制剂。然而，PBTZ类似物的合成需要大量的纯化步骤，危险试剂的使用以及对环境不可持续的废物的产生。 考虑到PBTZ类似物的有希望的抗病毒活性需要进一步探索，在这项工作中，我们报告了一种新的可持续的三组分反应（3CR）的开发，该反应可以与一锅法中的碱性水解反应结合使用PBTZ支架，从而减少了合成步骤，提高了产量并节省了时间。为了通过使用不同的起始材料来证明其广泛的应用范围，对3CR进行了广泛的研究。此外，利用这些程序，我们接下来设计和合成了一组新的PBTZ类似物，这些类似物已作为抗DE

  DOI：

  10.1016/j.ejmech.2020.112992
• 作为产物：
  描述：

  2-甲基-5-苯并噻唑 在 水 、 三乙胺 、 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙二醇 为溶剂， 反应 96.0h， 生成 8-(cyclohexyloxy)-1-oxo-2-phenyl-1H-pyrido[2,1-b][1,3]benzothiazole-4-carboxylic acid
  参考文献：
  名称：

  Pyridobenzothiazole derivatives as new chemotype targeting the HCV NS5B polymerase

  摘要：

  Hepatitis C virus (HCV) infection has been recognized as the major cause of liver failure that can lead to hepatocellular carcinoma. Among all the HCV proteins, NS5B polymerase represents a leading target for drug discovery strategies. Herein, we describe our initial research efforts towards the identification of new chemotypes as allosteric NS5B inhibitors. In particular, the design, synthesis, in vitro anti-NS5B and in cellulo anti-HCV evaluation of a series of 1-oxo-1H-pyrido[2,1-b][1,3]benzothiazole-4-carboxylate derivatives are reported. Some of the newly synthesized compounds showed an IC50 ranging from 11 to 23 mu M, and molecular modeling and biochemical studies suggested that the thumb domain could be the target site for this new class of NS5B inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.061

文献信息

• Pyridobenzothiazolones Exert Potent Anti-Dengue Activity by Hampering Multiple Functions of NS5 Polymerase
  作者：Rolando Cannalire、Kitti Wing Ki Chan、Maria Sole Burali、Chin Piaw Gwee、Sai Wang、Andrea Astolfi、Serena Massari、Stefano Sabatini、Oriana Tabarrini、Eloise Mastrangelo、Maria Letizia Barreca、Violetta Cecchetti、Subhash G. Vasudevan、Giuseppe Manfroni

  DOI：10.1021/acsmedchemlett.9b00619

  日期：2020.5.14

  Treatment of dengue virus (DENY) and other flavivirus infections is an unmet medical need. The highly conserved flaviviral NS5 RNA-dependent RNA polymerase (RdRp) is an attractive antiviral target that interacts with NS3 and viral RNA within the replication complex assembly. Biochemical and cell-based evidence indicate that targeting cavity B may lead to dual RdRp and NS5-NS3 interaction inhibitors. By ligand-based design around 1H-pyrido[2,1-b][1,3]benzothiazol-1-one (PBTZ) 1, we identified new potent and selective DENY inhibitors that exert dual inhibition of NS5 RdRp and NS3-NS5 interaction, likely through binding cavity B. Resistance studies with compound 4 generated sequence variants in the 3'-untranslated region of RNA while further biochemical experiments demonstrated its ability to block also RNA-NS5 interaction, required for correct RNA synthesis in cells. These findings shed light on the potential mechanism of action for this class of compounds, underlying how PBTZs are very promising lead candidates for further evaluation.
• Targeting flavivirus RNA dependent RNA polymerase through a pyridobenzothiazole inhibitor
  作者：Delia Tarantino、Rolando Cannalire、Eloise Mastrangelo、Romina Croci、Gilles Querat、Maria Letizia Barreca、Martino Bolognesi、Giuseppe Manfroni、Violetta Cecchetti、Mario Milani

  DOI：10.1016/j.antiviral.2016.09.007

  日期：2016.10

  RNA dependent RNA polymerases (RdRp) are essential enzymes for flavivirus replication. Starting from an in silico docking analysis we identified a pyridobenzothiazole compound, HeE1-2Tyr, able to inhibit West Nile and Dengue RdRps activity in vitro, which proved effective against different flaviviruses in cell culture. Crystallographic data show that HeE1-2Tyr binds between the fingers domain and the priming loop of Dengue virus RdRp (Site 1). Conversely, enzyme kinetics, binding studies and mutational analyses suggest that, during the catalytic cycle and assembly of the RdRp-RNA complex, HeE1-2Tyr might be hosted in a distinct binding site (Site 2). RdRp mutational studies, driven by in silico docking analysis, allowed us to locate the inhibition Site 2 in the thumb domain. Taken together, our results provide innovative concepts for optimization of a new class of anti-flavivirus compounds. (C) 2016 The Authors. Published by Elsevier B.V.
• Sustainable, three-component, one-pot procedure to obtain active anti-flavivirus agents
  作者：Tommaso Felicetti、Maria Sole Burali、Chin Piaw Gwee、Kitti Wing Ki Chan、Sylvie Alonso、Serena Massari、Stefano Sabatini、Oriana Tabarrini、Maria Letizia Barreca、Violetta Cecchetti、Subhash G. Vasudevan、Giuseppe Manfroni

  DOI：10.1016/j.ejmech.2020.112992

  日期：2021.1

  number of purification steps, the use of hazardous reagents and environmentally unsustainable generation of waste. Considering the promising antiviral activity of PBTZ analogues which require further exploration, in this work, we report the development of a new and sustainable three-component reaction (3CR) that can be combined with a basic hydrolysis in a one-pot procedure to obtain the PBTZ scaffold

  属于黄病毒属的蚊媒病毒，例如登革热病毒（DENV）和寨卡病毒（ZIKV），会引起人类感染，从轻度的流感样症状到出血热，肝炎和神经病。迄今为止，只有少数黄病毒的疫苗，而没有有效的治疗方法。 吡啶并苯并噻唑（PBTZ）衍生物是一类具有广阔前景的广谱抗黄病毒活性的化合物，据报道，其中大多数是黄病毒NS5聚合酶的有效抑制剂。然而，PBTZ类似物的合成需要大量的纯化步骤，危险试剂的使用以及对环境不可持续的废物的产生。 考虑到PBTZ类似物的有希望的抗病毒活性需要进一步探索，在这项工作中，我们报告了一种新的可持续的三组分反应（3CR）的开发，该反应可以与一锅法中的碱性水解反应结合使用PBTZ支架，从而减少了合成步骤，提高了产量并节省了时间。为了通过使用不同的起始材料来证明其广泛的应用范围，对3CR进行了广泛的研究。此外，利用这些程序，我们接下来设计和合成了一组新的PBTZ类似物，这些类似物已作为抗DE
• Pyridobenzothiazole derivatives as new chemotype targeting the HCV NS5B polymerase
  作者：Giuseppe Manfroni、Francesco Meschini、Maria Letizia Barreca、Pieter Leyssen、Alberta Samuele、Nunzio Iraci、Stefano Sabatini、Serena Massari、Giovanni Maga、Johan Neyts、Violetta Cecchetti

  DOI：10.1016/j.bmc.2011.11.061

  日期：2012.1

  Hepatitis C virus (HCV) infection has been recognized as the major cause of liver failure that can lead to hepatocellular carcinoma. Among all the HCV proteins, NS5B polymerase represents a leading target for drug discovery strategies. Herein, we describe our initial research efforts towards the identification of new chemotypes as allosteric NS5B inhibitors. In particular, the design, synthesis, in vitro anti-NS5B and in cellulo anti-HCV evaluation of a series of 1-oxo-1H-pyrido[2,1-b][1,3]benzothiazole-4-carboxylate derivatives are reported. Some of the newly synthesized compounds showed an IC50 ranging from 11 to 23 mu M, and molecular modeling and biochemical studies suggested that the thumb domain could be the target site for this new class of NS5B inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.