6,6-Dimethyl-1-(pyrazol-3-yl)-3-((thiazol-2-yl)thio)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6,6-Dimethyl-1-(pyrazol-3-yl)-3-((thiazol-2-yl)thio)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
• 英文别名: 6,6-Dimethyl-1-(1H-pyrazol-3-yl)-3-(thiazol-2-ylsulfanyl)-6,7-dihydro-5H-benzo[c]thiophen-4-one；6,6-dimethyl-1-(1H-pyrazol-5-yl)-3-(1,3-thiazol-2-ylsulfanyl)-5,7-dihydro-2-benzothiophen-4-one
• 化学式: C₁₆H₁₅N₃OS₃
• 分子量: 361.513
• InChiKey: LBVOFGFYNPOQHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  140
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6,6-dimethyl-3-methylthio-1-(pyrazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 反应 72.0h， 生成 6,6-Dimethyl-1-(pyrazol-3-yl)-3-((thiazol-2-yl)thio)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
  参考文献：
  名称：

  6,7-Dihydro-2-benzothiophen-4(5H)-ones:  A Novel Class of GABA-A α5 Receptor Inverse Agonists

  摘要：

  Nonselective inverse agonists at the benzodiazepine binding site on the GABA-A chloride ion channel enhance cognitive performance in animals but cannot be used in the treatment of cognitive disorders because of anxiogenic and convulsant side effects. We have identified a novel series of GABA-A alpha5 receptor ligands during our search for alpha5 receptor inverse agonists as potential cognition enhancers. In particular, 6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro- 2-benzothiophen-4(5H-)-one (26) has been identified as a functionally selective GABA-A alpha5 inverse agonist.

  DOI：

  10.1021/jm010471b

文献信息

• 6,7-Dihydro-2-benzothiophen-4(5<i>H</i>)-ones:  A Novel Class of GABA-A α5 Receptor Inverse Agonists
  作者：Mark S. Chambers、John R. Atack、Frances A. Bromidge、Howard B. Broughton、Susan Cook、Gerard R. Dawson、Sarah C. Hobbs、Karen A. Maubach、Austin J. Reeve、Guy R. Seabrook、Keith Wafford、Angus M. MacLeod

  DOI：10.1021/jm010471b

  日期：2002.3.1

  Nonselective inverse agonists at the benzodiazepine binding site on the GABA-A chloride ion channel enhance cognitive performance in animals but cannot be used in the treatment of cognitive disorders because of anxiogenic and convulsant side effects. We have identified a novel series of GABA-A alpha5 receptor ligands during our search for alpha5 receptor inverse agonists as potential cognition enhancers. In particular, 6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro- 2-benzothiophen-4(5H-)-one (26) has been identified as a functionally selective GABA-A alpha5 inverse agonist.
• THIENYLCYCLOHEXANONE DERIVATIVES AS LIGANDS OF THE GABA A alpha5 RECEPTOR SUBTYPE
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0937072B1

  公开（公告）日：2002-01-09
• US6262103B1
  申请人：——

  公开号：US6262103B1

  公开（公告）日：2001-07-17
• Identification of a Novel, Selective GABA_A α5 Receptor Inverse Agonist Which Enhances Cognition
  作者：Mark S. Chambers、John R. Atack、Howard B. Broughton、Neil Collinson、Susan Cook、Gerard R. Dawson、Sarah C. Hobbs、George Marshall、Karen A. Maubach、Goplan V. Pillai、Austin J. Reeve、Angus M. MacLeod

  DOI：10.1021/jm020582q

  日期：2003.5.1

  In pursuit of a GABA(A) alpha5-subtype-selective inverse agonist to enhance cognition, a series of 6,7-dihydro-2-benzothiophen-4(5H)-ones has been identified as a novel class of GABAA receptor ligands. These thiophenes have higher binding affinity for the GABA(A) alpha(5) receptor subtype compared to the GABA(A) alpha(1), alpha(2), and alpha(3) subtypes, and several analogues exhibit high GABA(A) (alpha(5) receptor inverse agonism. 6,6-Dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro2-benzothiophen-4(5H)-one (43) has been identified as a full inverse agonist at the GABA(A) alpha5 receptor and is functionally selective over the other major GABA(A) receptor subtypes. 43 readily penetrates into the CNS to give selective occupancy of GABA(A) alpha5 receptors. In addition, 43 enhances cognitive performance in rats in the delayed 'matching-to-place' Morris water maze test-a hippocampal-dependent memory task-without the convulsant or proconvulsant activity associated with nonselective, GABA(A) receptor inverse agonists.