2-amino-6-ethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide | 328270-02-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 2-amino-6-ethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide
• 英文别名: 2-amino-6-ethyl-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid amide；2-Amino-6-ethyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide
• CAS: 328270-02-6
• 化学式: C₁₁H₁₆N₂OS
• mdl: MFCD01335773
• 分子量: 224.327
• InChiKey: DDTYZCRSUWTPDY-UHFFFAOYSA-N

物化性质

• 沸点：
  349.9±42.0 °C(Predicted)
• 密度：
  1.217±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  97.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2-amino-6-ethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 在 四氯苯醌 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以45%的产率得到2-Amino-6-ethyl-1-benzothiophene-3-carboxamide
  参考文献：
  名称：

  Discovery of Novel Fibroblast Growth Factor Receptor 1 Kinase Inhibitors by Structure-Based Virtual Screening

  摘要：

  Fibroblast growth factors (FGFs) play important roles in embryonic development, angiogenesis, wound healing, and cell proliferation and differentiation. In search of inhibitors of FGFR1 kinase, 2.2 million compounds were docked into the ATP binding site of the protein. A co-crystal structure, which shows two alternative conformations for the nucleotide binding loop, is reported. Docking was performed oil both conformations and, ultimately, 23 diverse compounds were purchased and assayed. Following hit validation, two compounds 10 and 16, a benzylidene derivative of pseudothiohydantoin and a thienopyrimidinone derivative, respectively, were discovered that inhibit FGFR1 kinase with IC50 values of 23 and 50 mu M. Initial optimization of 16 led to the more unsaturated 40, which has significantly enhanced potency, 1.9 mu M. The core structures represent new structural motifs for FGFR1 kinase inhibitors. The study also illustrates complexities associated with the choice of protein structures for docking, possible use of multiple kinase structures to seek selectivity, and hit identification.

  DOI：

  10.1021/jm901386e
• 作为产物：
  描述：

  3-乙基环己酮 、 氰乙酰胺 在 吗啉 、 sulfur 作用下， 以 乙醇 为溶剂， 以79%的产率得到2-amino-6-ethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide
  参考文献：
  名称：

  Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase

  摘要：

  Influenza viruses (Flu) are responsible for seasonal epidemics causing high rates of morbidity, which can dramatically increase during severe pandemic outbreaks. Antiviral drugs are an indispensable weapon to treat infected people and reduce the impact on human health, nevertheless anti-Flu armamentarium still remains inadequate. In search for new anti-Flu drugs, our group has focused on viral RNA-dependent RNA polymerase (RdRP) developing disruptors of PA-PB1 subunits interface with the best compounds characterized by cycloheptathiophene-3-carboxamide and 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide scaffolds. By merging these moieties, two very interesting hybrid compounds were recently identified, starting from which, in this paper, a series of analogues were designed and synthesized. In particular, a thorough exploration of the cycloheptathiophene-3-carboxamide moiety led to acquire important SAR insight and identify new active compounds showing both the ability to inhibit PA-PB1 interaction and viral replication in the micromolar range and at non-toxic concentrations. For few compounds, the ability to efficiently inhibit PA-PB1 subunits interaction did not translate into anti-Flu activity. Chemical/physical properties were investigated for a couple of compounds suggesting that the low solubility of compound 14, due to a strong crystal lattice, may have impaired its antiviral activity. Finally, computational studies performed on compound 23, in which the phenyl ring suitably replaced the cycloheptathiophene, suggested that, in addition to hydrophobic interactions, H-bonds enhanced its binding within the PAC cavity.

  DOI：

  10.1016/j.ejmech.2020.112944

文献信息

• Parallel synthesis and biological evaluation of 5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-one cytotoxic agents selective for p21-deficient cells
  作者：Lee D. Jennings、Scott L. Kincaid、Yanong D. Wang、Girija Krishnamurthy、Carl F. Beyer、John P. McGinnis、Miriam Miranda、Carolyn M. Discafani、Sridhar K. Rabindran

  DOI：10.1016/j.bmcl.2005.07.072

  日期：2005.11

  cycle checkpoint-disrupted cells vs. cells with intact p21 checkpoint, were identified by high-throughput screening. Optimization of both ends of the lead molecule to improve potency, using parallel synthesis and iterative design, is described. The 2-(1,4-dibenzodioxane)-substituted derivative 14 was identified as a highly selective and potent agent displaying an IC50 of 91 nM in the p21-deficient cell

  通过高通量筛选，鉴定出了一系列针对p21细胞周期检查点破坏的细胞和具有完整p21检查点的细胞具有选择性的癌细胞增殖抑制剂。描述了使用平行合成和迭代设计优化前导分子两端以提高效能的方法。2-（1,4-二苯并二恶烷）-取代的衍生物14被鉴定为高度有效的选择性药物，在缺乏p21的细胞系中显示出IC50为91 nM。
• Identification of PDE4B Over 4D subtype-selective inhibitors revealing an unprecedented binding mode
  作者：Michael Kranz、Michael Wall、Brian Evans、Afjal Miah、Stuart Ballantine、Chris Delves、Brian Dombroski、Jeffrey Gross、Jessica Schneck、James P. Villa、Margarete Neu、Don O. Somers

  DOI：10.1016/j.bmc.2009.03.061

  日期：2009.7

  A PDE4B over 4D-selective inhibitor programme was initiated to capitalise on the recently discovered predominance of the PDE4B subtype in inflammatory cell regulation. The SAR of a tetrahydrobenzothiophene (THBT) series did not agree with either of two proposed docking modes in the 4B binding site. A subsequent X-ray co- crystal structure determination revealed that the THBT ligand displaces the Gln-443 residue, invariably ligand-anchoring in previous PDE4 co-crystal structures, and even shifts helix-15 by 1-2 angstrom. For the first time, several residues of the C-terminus previously proposed to be involved in subtype selectivity are resolved and three of them extend into the ligand binding site potentially allowing for selective drug design. (C) 2009 Elsevier Ltd. All rights reserved.
• Inhibitors of MALT1-proteolytic activity and uses thereof
  申请人：VIB VZW

  公开号：EP2222326B1

  公开（公告）日：2012-04-18
• INHIBITORS OF MALT1 PROTEOLYTIC ACTIVITY AND USES THEREOF
  申请人：VIB VZW

  公开号：EP2222326B2

  公开（公告）日：2015-02-25