4-(3-phenylphenyl)thieno[2,3-c]pyridine-2-carboxamide | 870235-82-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3-phenylphenyl)thieno[2,3-c]pyridine-2-carboxamide
• CAS: 870235-82-8
• 化学式: C₂₀H₁₄N₂OS
• 分子量: 330.41
• InChiKey: NUNDFMJANFGRPS-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：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-phenylphenyl)thieno[2,3-c]pyridine-2-carboxamide 在 吡啶 、 三氟乙酸 作用下， 反应 6.0h， 生成 4-(3-phenylphenyl)thieno[2,3-c]pyridine-2-carbonitrile
  参考文献：
  名称：

  Identification of a selective thieno[2,3-c]pyridine inhibitor of COT kinase and TNF-α production

  摘要：

  COT (Tpl2 in mice) is a serine/threonine MAP3 kinase that regulates production of TNF-alpha and other pro-inflammatory cytokines such as IL-1 beta via the ERK/MAP kinase pathway. As TNF-alpha and IL-1 beta are clinically validated targets for therapeutic intervention in rheumatoid arthritis (RA), blocking COT provides a potential avenue for amelioration of disease. Herein we describe identification of a cellular active selective small molecule inhibitor of COT kinase. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.088
• 作为产物：
  描述：

  methyl 4-([1,1'-biphenyl]-3-yl)thieno[2,3-c]pyridine-2-carboxylate 在 氨 作用下， 以 甲醇 为溶剂， 生成 4-(3-phenylphenyl)thieno[2,3-c]pyridine-2-carboxamide
  参考文献：
  名称：

  Identification of a selective thieno[2,3-c]pyridine inhibitor of COT kinase and TNF-α production

  摘要：

  COT (Tpl2 in mice) is a serine/threonine MAP3 kinase that regulates production of TNF-alpha and other pro-inflammatory cytokines such as IL-1 beta via the ERK/MAP kinase pathway. As TNF-alpha and IL-1 beta are clinically validated targets for therapeutic intervention in rheumatoid arthritis (RA), blocking COT provides a potential avenue for amelioration of disease. Herein we describe identification of a cellular active selective small molecule inhibitor of COT kinase. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.088

文献信息

• Identification and Optimization of Thienopyridine Carboxamides as Inhibitors of HIV Regulatory Complexes
  作者：Robert L. Nakamura、Mark A. Burlingame、Shumin Yang、David C. Crosby、Dale J. Talbot、Kitty Chui、Alan D. Frankel、Adam R. Renslo

  DOI：10.1128/aac.02366-16

  日期：2017.7

  Viral regulatory complexes perform critical functions during virus replication and are important targets for therapeutic intervention. In HIV, the Tat and Rev proteins form complexes with multiple viral and cellular factors to direct transcription and export of the viral RNA. These complexes are composed of many proteins and are dynamic, making them difficult to fully recapitulate in vitro . Therefore, we developed a cell-based reporter assay to monitor the assembly of viral complexes for inhibitor screening. We screened a small-molecule library and identified multiple hits that inhibit the activity of the viral complexes. A subsequent chemistry effort was focused on a thieno[2,3-b]pyridine scaffold, examples of which inhibited HIV replication and the emergence from viral latency. Notable aspects of the effort to determine the structure-activity relationship (SAR) include migration to the regioisomeric thieno[2,3-c]pyridine ring system and the identification of analogs with single-digit nanomolar activity in both reporter and HIV infectivity assays, an improvement of >100-fold in potency over the original hits. These results validate the screening strategy employed and reveal a promising lead series for the development of a new class of HIV therapeutics.

  摘要 病毒调控复合物在病毒复制过程中发挥着关键作用，是治疗干预的重要目标。在艾滋病毒中，Tat 和 Rev 蛋白与多种病毒和细胞因子形成复合物，指导病毒 RNA 的转录和输出。这些复合物由许多蛋白质组成，并且是动态的，因此很难在体外完全重现。 体外 .因此，我们开发了一种基于细胞的报告检测方法来监测病毒复合物的组装，以筛选抑制剂。我们筛选了一个小分子化合物库，发现了多个能抑制病毒复合物活性的化合物。随后的化学研究工作集中在噻吩并[2,3-b]吡啶支架上，其中的一些例子抑制了艾滋病毒的复制和病毒潜伏期的出现。在确定结构-活性关系（SAR）的工作中，值得注意的方面包括向噻吩并[2,3-c]吡啶环系统的异构体迁移，以及在报告和 HIV 感染性试验中鉴定出具有个位数纳摩尔活性的类似物，与最初的结果相比，药效提高了 100 倍。这些结果验证了所采用的筛选策略，并揭示了开发一类新型艾滋病治疗药物的前景广阔的先导系列。
• COMPOUNDS AND METHODS FOR TREATING HIV INFECTION
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20180015077A1

  公开（公告）日：2018-01-18

  Provided herein, inter alia, are methods and compounds for treating an HIV infection.

  本文提供了用于治疗HIV感染的方法和化合物，其中包括。
• Identification of a selective thieno[2,3-c]pyridine inhibitor of COT kinase and TNF-α production
  作者：Kevin Cusack、Hamish Allen、Agnieszka Bischoff、Anca Clabbers、Richard Dixon、Shannon Fix-Stenzel、Michael Friedman、Yvette Gaumont、Dawn George、Thomas Gordon、Pintipa Grongsaard、Bernd Janssen、Yong Jia、Maria Moskey、Christopher Quinn、Andres Salmeron、Christine Thomas、Grier Wallace、Neil Wishart、Zhengtian Yu

  DOI：10.1016/j.bmcl.2009.01.088

  日期：2009.3

  COT (Tpl2 in mice) is a serine/threonine MAP3 kinase that regulates production of TNF-alpha and other pro-inflammatory cytokines such as IL-1 beta via the ERK/MAP kinase pathway. As TNF-alpha and IL-1 beta are clinically validated targets for therapeutic intervention in rheumatoid arthritis (RA), blocking COT provides a potential avenue for amelioration of disease. Herein we describe identification of a cellular active selective small molecule inhibitor of COT kinase. (C) 2009 Elsevier Ltd. All rights reserved.