6,6-Dimethyl-3-isopropylthio-1-(pyrazol-3-yl)-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-3-isopropylthio-1-(pyrazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
• 英文别名: 6,6-dimethyl-3-(propan-2-ylsulfanyl)-1-(1H-pyrazol-3-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one；3-Isopropylsulfanyl-6,6-dimethyl-1-(1H-pyrazol-3-yl)-6,7-dihydro-5H-benzo[c]thiophen-4-one；6,6-dimethyl-3-propan-2-ylsulfanyl-1-(1H-pyrazol-5-yl)-5,7-dihydro-2-benzothiophen-4-one
• 化学式: C₁₆H₂₀N₂OS₂
• 分子量: 320.48
• InChiKey: CNFLHWVYIFARIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  99.3
• 氢给体数：
  1
• 氢受体数：
  4

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 、 间氯过氧苯甲酸 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 6,6-Dimethyl-3-isopropylthio-1-(pyrazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
  参考文献：
  名称：

  Identification of a Novel, Selective GABA_A α5 Receptor Inverse Agonist Which Enhances Cognition

  摘要：

  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.

  DOI：

  10.1021/jm020582q

文献信息

• [EN] COMPOUNDS INHIBITING LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY<br/>[FR] COMPOSÉS INHIBANT L'ACTIVITÉ ENZYMATIQUE DE LA KINASE À MOTIFS RÉPÉTÉS RICHES EN LEUCINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2012118679A1

  公开（公告）日：2012-09-07

  Disclosed are compounds of Formula I: and the pharmaceutically acceptable salts thereof, wherein "A" is S-; -SO-, -SO2-, -O- or NRa-, and Ra, and R1 through R5 are defined herein. Also disclosed are pharmaceutical formulations comprising a compound of Formula I and methods of treating, managing, or ameliorating diseases amenable to treatment, management, or amelioration by inhibition of LRRK2 kinase activity, for example, Parkinson's disease.

  本文披露了Formula I的化合物及其药用盐，其中“A”为S-；-SO-；-SO2-；-O-或NRa-，而Ra和R1至R5在此定义。还披露了包括Formula I化合物的药物配方，以及通过抑制LRRK2激酶活性来治疗、管理或改善可通过此方式治疗、管理或改善的疾病的方法，例如帕金森病。
• [EN] THIENYLCYCLOHEXANONE DERIVATIVES AS LIGANDS OF THE GABAA alpha 5 RECEPTOR SUBTYPE<br/>[FR] DERIVES DE LA THIENYLCYCLOHEXANONE UTILISES COMME LIGANDS DU SOUS-TYPE alpha -5 DE RECEPTEUR DU GABAA
  申请人：MERCK SHARP & DOHME LIMITED

  公开号：WO1998018792A1

  公开（公告）日：1998-05-07

  (EN) The present invention provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein A is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, arylC1-6alkyl, aryl, S(O)pR1.(FR) L'invention concerne une composition pharmaceutique contenant un composé de formule (I), dans laquelle A est alkyle C1-C6, alkényle C2-C6, alkynyle C2-C6, cycloalkyle C3-C6, arylalkyle C1-C6, aryle, S(O)pR1, ou un sel pharmaceutiquement acceptable dudit composé.

  该发明提供了一种药物组合物，包括公式（I）的化合物或其药学上可接受的盐，其中A为C1-6烷基，C2-6烯基，C2-6炔基，C3-6环烷基，芳基C1-6烷基，芳基，S（O）pR1。
• 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? $g(a)5 RECEPTOR SUBTYPE
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0937072A1

  公开（公告）日：1999-08-25
• 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