6,6-Dimethyl-3-methylthio-1-(1-methyl-1,2,4-triazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one | 207306-69-2

• 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-methylthio-1-(1-methyl-1,2,4-triazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
• 英文别名: 6,6-Dimethyl-3-methylsulfanyl-1-(1-methyl-1H-[1,2,4]triazol-3-yl)-6,7-dihydro-5H-benzo[c]thiophen-4-one；6,6-dimethyl-3-methylsulfanyl-1-(1-methyl-1,2,4-triazol-3-yl)-5,7-dihydro-2-benzothiophen-4-one
• CAS: 207306-69-2
• 化学式: C₁₄H₁₇N₃OS₂
• 分子量: 307.44
• InChiKey: HRUDFUBJGCKXQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6,6-Dimethyl-3-methylthio-1-(1-methyl-1,2,4-triazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one 以38%的产率得到6,6-dimethyl-5-hydroxymethylene-3-methylthio-1-(1-methyl-1,2,4-triazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
  参考文献：
  名称：

  Substituted thienobenzisoxazole derivatives for enhancing cognition

  摘要：

  本发明提供了式(I)的化合物及其药学上可接受的盐：##STR1##其中A为C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.3-6环烷基，芳基C.sub.1-6烷基，芳基，S(O).sub.p R.sup.1，OR.sup.1或NR.sup.1 R.sup.12；B为可选择取代的5-或6-成员杂芳环或C(O)NR.sup.10 R.sup.11；R.sup.1为氢，可选择取代的C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.3-6环烷基或C.sub.3-6环烯基，可选择取代的芳基，芳基C.sub.1-6烷基，芳基C.sub.2-6烯基或芳基C.sub.2-6炔基或可选择取代的5-或6-成员杂芳环；R.sup.2和R.sup.3为氢或C.sub.1-6烷基；R.sup.4为氢，C.sub.1-8烷基，C.sub.2-8烯基，C.sub.2-8炔基，芳基或CH.sub.2(CO).sub.m NR.sup.8 R.sup.9；R.sup.5为NR.sup.6 R.sup.7，C.sub.1-6烷基或C.sub.1-6烷氧基；R.sup.6独立定义为R.sup.4；R.sup.7为芳基，可选择取代的卤素，硝基或氰基；R.sup.8为氢，C.sub.1-6烷基，C.sub.3-6环烷基，C.sub.3-6环烯基，C.sub.2-6烯基，C.sub.2-6炔基；芳基C.sub.1-6烷基，芳基C.sub.2-6烯基或芳基C.sub.2-6炔基，可选择取代的卤素，硝基或氰基的芳基环；噻吩或吡啶；R.sup.9为C.sub.1-6烷基；C.sub.2-烯基；C.sub.2-6炔基；或苯基，可选择取代为一个，两个或三个独立选择的卤素，CF.sub.3，OCH.sub.3，硝基和氰基；R.sup.10和R.sup.11分别为氢，C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基或C.sub.3-8环烷基或R.sup.10和R.sup.11，与它们连接的氮原子一起形成饱和的4到8成员环，可选择包含一个氧原子或另一个氮原子作为环成员，另一个氮原子未取代或取代为C.sub.1-4烷基，C.sub.2-4烯基或C.sub.2-4炔基；R.sup.12为氢或C.sub.1-6烷基；m为零或1；p为零，1或2；q为0，1或2；r为0，1或2；这些化合物的制备，它们在增强认知能力中的应用，特别是在疾病状态下，尤其是阿尔茨海默病中的治疗方法。

  公开号：

  US06143773A1
• 作为产物：
  描述：

  6,6-dimethyl-3-methylthio-4-oxo-4,5,6,7-tetrahydro-2-benzothiophene-1-carbothioamide 以 乙醇 、 水 为溶剂， 反应 41.0h， 生成 6,6-Dimethyl-3-methylthio-1-(1-methyl-1,2,4-triazol-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

• Thienycyclohexanone derivatives as ligands of the GABAA &agr;5 receptor subtype
  申请人：Merck Sharp & Dohme Limited

  公开号：US06262103B1

  公开（公告）日：2001-07-17

  A pharamceutical composition comprises a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein A is C1-6alkyl, C2-6alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, arylC1-6alkyl, aryl, S(O)pR1.

  一种药物组合物包括式(I)的化合物或其药学上可接受的盐，其中A是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。
• 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
• US6143773A
  申请人：——

  公开号：US6143773A

  公开（公告）日：2000-11-07
• US6262103B1
  申请人：——

  公开号：US6262103B1

  公开（公告）日：2001-07-17