tetrahydrobenzothiophene (THBT), 25 | 1186467-47-9

• 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: tetrahydrobenzothiophene (THBT), 25
• 英文别名: 2-[(2-nitrobenzoyl)amino]-6-phenyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide
• CAS: 1186467-47-9
• 化学式: C₂₂H₁₉N₃O₄S
• 分子量: 421.477
• InChiKey: WEUREFIAMIPTHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-苯基环己酮 、 2-硝基苯甲酰氯 、 氰乙酰胺 在 吗啉 、 sulfur 、 吡啶 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 tetrahydrobenzothiophene (THBT), 25
  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

• 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.