2-Amino-5-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide | 70733-09-4

• 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-5-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide
• 英文别名: 2-amino-5-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide
• CAS: 70733-09-4
• 化学式: C₁₀H₁₄N₂OS
• 分子量: 210.3
• InChiKey: MCIXNCZSSYQKMG-UHFFFAOYSA-N

物化性质

• 熔点：
  196 °C(Solv: ethanol (64-17-5))
• 沸点：
  336.1±42.0 °C(Predicted)
• 密度：
  1.261±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  97.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Amino-5-methyl-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47%的产率得到2-Amino-5-methyl-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：

  氰乙酰胺 、 3-甲基环己酮 在 吗啉 、 sulfur 作用下， 以 乙醇 为溶剂， 生成 2-Amino-5-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide
  参考文献：
  名称：

  Identification of PDE4B Over 4D subtype-selective inhibitors revealing an unprecedented binding mode

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2009.03.061

文献信息

• Novel therapeutic targets for the treatment of mycobacterial infections and compounds useful therefor
  申请人：——

  公开号：US20040171603A1

  公开（公告）日：2004-09-02

  Described herein is the discovery that certain mycobacterial serine/threonine protein kinases, particularly protein kinase G (PknG), are effective therapeutic targets for the treatment of mycobacterial infections. Furthermore, the present application refers to the use of mycobacterial serine/threonine protein kinases for developing methods for detection and determination of these kinases for recognizing and monitoring diseases and for controlling therapy of diseases. Additionally disclosed are novel 4,5,6,7-tetrahydrobenzo[b]thiophene compounds, benzo(g)quinoxaline compounds, and pharmaceutically acceptable salts thereof, and methods of using such compounds and salts thereof for the prophylaxis and/or treatment of virally and/or bacterially induced infections, particularly mycobacteria-induced infections, including opportunistic infections, as well as pharmaceutical compositions containing at least one 4,5,6,7-tetrahydrobenzo[b]thiophene compound and/or benzo(g)quinoxaline compound and/or pharmaceutically acceptable salts thereof in a pharmaceutically acceptable carrier.

  本文描述的是发现某些分枝杆菌丝氨酸/苏氨酸蛋白激酶，特别是蛋白激酶 G (PknG)，是治疗分枝杆菌感染的有效治疗靶点。此外，本申请还涉及利用分枝杆菌丝氨酸/苏氨酸蛋白激酶开发检测和测定这些激酶的方法，用于识别和监测疾病以及控制疾病的治疗。此外，还公开了新型 4,5,6,7-四氢苯并[b]噻吩化合物、苯并（g）喹喔啉化合物及其药学上可接受的盐，以及使用此类化合物及其盐预防和/或治疗病毒和/或细菌引起的感染，特别是分枝杆菌引起的感染（包括机会性感染）的方法，以及含有至少一种 4,5,6,7-四氢苯并&lsqb；b]噻吩化合物和/或苯并(g)喹喔啉化合物和/或其药学上可接受的盐，并将其置于药学上可接受的载体中。
• Perrissin; Favre; Luu-Duc, European Journal of Medicinal Chemistry, 1984, vol. 19, # 5, p. 420 - 424
  作者：Perrissin、Favre、Luu-Duc、et al.

  DOI：——

  日期：——
• PERRISSIN, M.;FAVRE, M.;LUU-DUC, CUONG;BAKRI-LOGEAIS, F.;HUGUET, F.;NARCI+, EUR. J. MED. CHEM., 1984, 19, N 5, 420-424
  作者：PERRISSIN, M.、FAVRE, M.、LUU-DUC, CUONG、BAKRI-LOGEAIS, F.、HUGUET, F.、NARCI+

  DOI：——

  日期：——
• 4,5,6,7-TRETRAHYDROBENZO(B) THIOPHENE DERIVATIVES AND METHODS FOR MEDICAL INTERVENTION AGAINST MYCROBACTERIAL INFECTIONS
  申请人：Axxima Pharmaceuticals AG

  公开号：EP1492783A1

  公开（公告）日：2005-01-05
• 4,5,6,7-tetrahydrobenzo[b]thiophene derivatives and methods for medical intervention against mycobacterial infections
  申请人：Missio Andrea

  公开号：US20090018149A1

  公开（公告）日：2009-01-15

  Described are 4,5,6,7-tetrahydrobenzo[b]thiophene derivatives and pharmaceutically acceptable salts thereof, the use of these derivatives for the prophylaxis and/or treatment of mycobacteria-induced infections and opportunistic infections, as well as compositions containing at least one 4,5,6,7-tetrahydrobenzo[b]thiophene derivative and/or pharmaceutically acceptable salts thereof. Furthermore, the present application refers to the use of mycobacterial protein serine/threonine kinases for developing methods for detection and determination of these kinases for recognising and monitoring diseases and for controlling therapy of diseases.