3-[(2-羟基乙基)硫基]-6,6-二甲基-1-(1,3-噻唑-2-基)-6,7-二氢-2-苯并噻吩-4(5H)-酮 | 207306-50-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 3-[(2-羟基乙基)硫基]-6,6-二甲基-1-(1,3-噻唑-2-基)-6,7-二氢-2-苯并噻吩-4(5H)-酮
• 英文名称: 6,6 dimethyl-3-(3-hydroxypropyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one
• 英文别名: TB21007；6,6-Dimethyl-3-[(2-hydroxyethyl)thio]-1-(thiazol-2-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one；6,7-Dihydro-3-[(2-hydroxyethyl)thio]-6,6-dimethyl-1-(2-thiazolyl)-benzo[C]thiophen-4(5H)-one；3-(2-hydroxyethylsulfanyl)-6,6-dimethyl-1-(1,3-thiazol-2-yl)-5,7-dihydro-2-benzothiophen-4-one
• CAS: 207306-50-1
• 化学式: C₁₅H₁₇NO₂S₃
• 分子量: 339.503
• InChiKey: QILRYFCEXLFIDS-UHFFFAOYSA-N

物化性质

• 熔点：
  175-177 °C
• 沸点：
  544.9±60.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：100 mM；乙醇：25 mM

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  132
• 氢给体数：
  1
• 氢受体数：
  6

制备方法与用途

TB-21007是一种针对GABAA受体α5β3γ2亚单位的反向激动剂，其Ki值为1.6纳摩尔。研究显示，TB-21007能够增强大鼠的空间记忆能力。

反应信息

• 作为产物：
  描述：

  6,6-Dimethyl-3-methylthio-1-(thiazol-2-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 5.5h， 生成 3-[(2-羟基乙基)硫基]-6,6-二甲基-1-(1,3-噻唑-2-基)-6,7-二氢-2-苯并噻吩-4(5H)-酮
  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

• [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。
• Composition and method for treating cognitive impairments in down syndrome subjects
  申请人：CNRS Centre National De La Recherche Scientifique

  公开号：EP2298296A1

  公开（公告）日：2011-03-23

  This application relates to compounds having inverse agonist functional selectivity for GABAA receptors containing the α5 subunit for use as a medicament in the treatment of cognitive impairments in subjects suffering from Down syndrome. The present application also relates to the use of compounds having inverse agonist functional selectivity for GABAA receptors containing the α5 subunit for the preparation of a medicament in the treatment of cognitive impairments in subjects suffering from Down syndrome. The application further relates to pharmaceutical compositions for treating cognitive impairments in subjects suffering from Down syndrome comprising a compounds having inverse agonist functional selectivity for GABAA receptors containing the α5 subunit, or suitable pharmaceutically acceptable salt thereof, a polyethoxylated castor oil and dimethyl sulfoxide (DMSO). The present application also describes methods for enhancing cognitive function, or treating or lessening the severity of cognitive impairments, in subjects suffering from Down syndrome by administering to a subject in need thereof a pharmaceutically effective amount of one or more compounds having inverse agonist functional selectivity for GABAA receptors containing the α5 subunit. More particularly, the present application is concerned with the treatment of cognitive impairments, such as impairment in memory, learning capacity or both, in subjects suffering from Down syndrome.

  本申请涉及对含有α5亚基的GABAA受体具有反向激动剂功能选择性的化合物，该化合物可用作治疗唐氏综合征患者认知障碍的药物。本申请还涉及对含α5亚基的GABAA受体具有逆激动剂功能选择性的化合物用于制备治疗唐氏综合征患者认知障碍的药物。本申请还涉及用于治疗唐氏综合征患者认知障碍的药物组合物，该组合物包含对含有 α5亚基的GABAA受体具有反向激动剂功能选择性的化合物或其合适的药学上可接受的盐、聚氧乙烯蓖麻油和二甲基亚砜（DMSO）。 本申请还描述了通过向有需要的受试者施用一种或多种对含α5亚基的GABAA受体具有反向激动剂功能选择性的化合物的药学有效量，从而增强唐氏综合征受试者的认知功能，或治疗或减轻认知障碍的严重程度的方法。更具体地说，本申请涉及治疗唐氏综合征患者的认知障碍，如记忆力、学习能力或两者均受损。
• Reducing memory loss in mammals suffering from alzheimer's disease
  申请人：The Penn State Research Foundation

  公开号：US10039756B2

  公开（公告）日：2018-08-07

  The disclosure relates to methods and compositions for reducing memory loss. Specifically, methods of using inhibitors of GAT-3 polypeptide activity to reduce memory loss in mammals suffering from Alzheimer's disease (AD) are provided. Further provided are methods for identifying a mammal as having AD by detecting the presence of an elevated level of gamma-aminobutyric acid (GABA) within a mammal's brain.

  本公开涉及减少记忆丧失的方法和组合物。具体而言，提供了使用 GAT-3 多肽活性抑制剂减少患有阿尔茨海默病（AD）的哺乳动物记忆力减退的方法。此外，还提供了通过检测哺乳动物脑内γ-氨基丁酸（GABA）水平是否升高来确定哺乳动物是否患有阿尔茨海默病的方法。
• Methods and compositions for treating a subject for central nervous system (CNS) injury
  申请人：Carmichael Stanley T.

  公开号：US10206921B2

  公开（公告）日：2019-02-19

  Methods for treating a central nervous system (CNS) injury in a subject are provided. Aspects of the methods include administering to the subject an effective amount of gamma aminobutyric acid (GABA) receptor signaling inhibitor to treat the subject for the CNS injury. Also provided are compositions finding use in embodiments of the methods. Methods and compositions of the invention find use in the treatment of a variety of different CNS injuries, including but not limited to, treating a subject for CNS injury associated with the occurrence of stroke.

  本文提供了治疗受试者中枢神经系统（CNS）损伤的方法。这些方法的各个方面包括向受试者施用有效量的γ-氨基丁酸（GABA）受体信号转导抑制剂，以治疗受试者的中枢神经系统损伤。此外，还提供了可用于本方法实施方案的组合物。本发明的方法和组合物可用于治疗各种不同的中枢神经系统损伤，包括但不限于治疗与中风发生相关的中枢神经系统损伤。
• Reducing memory loss in mammals suffering from Alzheimer's disease
  申请人：The Penn State Research Foundation

  公开号：US10813922B2

  公开（公告）日：2020-10-27

  This document relates to methods and materials for reducing memory loss. For example, methods and materials for using inhibitors of GAT-3 polypeptide activity to reduce memory loss in mammals suffering from Alzheimer's disease are provided.

  本文涉及减少记忆力衰退的方法和材料。例如，提供了使用 GAT-3 多肽活性抑制剂减少患有阿尔茨海默氏症的哺乳动物记忆力衰退的方法和材料。