5-(1H-苯并咪唑-6-基)-1,3,4-恶二唑-2(3H)-硫酮 | 606091-78-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 5-(1H-苯并咪唑-6-基)-1,3,4-恶二唑-2(3H)-硫酮
• 英文名称: 5-(1H-benzo[d]imidazol-6-yl)-1,3,4-oxadiazole-2-thiol
• 英文别名: 5-(1H-Benzo[d]imidazol-6-yl)-1,3,4-oxadiazole-2(3H)-thione；5-(3H-benzimidazol-5-yl)-3H-1,3,4-oxadiazole-2-thione
• CAS: 606091-78-5
• 化学式: C₉H₆N₄OS
• 分子量: 218.239
• InChiKey: DQEZONNIYRJOSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  94.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(1H-苯并咪唑-6-基)-1,3,4-恶二唑-2(3H)-硫酮 、 3,4,5-三氟溴苄 在 三乙胺 作用下， 以 乙醇 为溶剂， 以76%的产率得到5-(5-(3,4,5-trifluorobenzylthio)-1,3,4-oxadiazol-2-yl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  WO2008/65141

  摘要：

  公开号：
• 作为产物：
  描述：

  1H-苯并咪唑-5-羧酸 在 硫酸 、 一水合肼 、 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 82.0h， 生成 5-(1H-苯并咪唑-6-基)-1,3,4-恶二唑-2(3H)-硫酮
  参考文献：
  名称：

  Structure–Activity Relationships of Benzimidazole-Based Glutaminyl Cyclase Inhibitors Featuring a Heteroaryl Scaffold

  摘要：

  Glutaminyl cyclase (hQC) has emerged as a new potential target for the treatment of Alzheimer's disease (AD). The inhibition of hQC prevents of the formation of the A beta(3(pE)-40,42) species which were shown to be of elevated neurotoidcity and are likely to act as a seeding core, leading to an accelerated formation of A beta-oligomers and fibrils. This work presents a new class of inhibitors of hQC, resulting from a pharmacophore-based screen. Hit molecules were identified, containing benzimidazole as the metal binding group connected to 1,3,4-oxadiazole as the central scaffold. The subsequent optimization resulted in benzimidazoly1-1,3,4-thiadiazoles and -1,2,3-triazoles with an inhibitory potency in the nanomolar range. Further investigation into the potential binding mode of the new compound classes combined molecular docking and site directed mutagenesis studies.

  DOI：

  10.1021/jm4001709

文献信息

• NOVEL INHIBITORS OF GLUTAMINYL CYCLASE
  申请人：Heiser Ulrich

  公开号：US20080214620A1

  公开（公告）日：2008-09-04

  The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, wherein R 1 represents heteroaryl, -carbocyclyl-heteroaryl, -alkenylheteroaryl or -alkylheteroaryl; R 2 represents alkyl; carbocyclyl which may optionally be substituted by alkyl; alkenyl; alkynyl, provided a triple bond is not adjacent to X; -alkyl-aryl; -alkyl-heteroaryl; -alkyl-heterocyclyl in which heterocyclyl may optionally be substituted by alkyl; -alkyl-carbocyclyl in which carbocyclyl may optionally be substituted by alkyl; aryl; heteroaryl; or H; X represents S or NR 3 ; R 3 represents H or C 1-4 alkyl.

  本发明涉及式（I）化合物、其组合物及用于疾病治疗的用途，其中R1代表杂环芳基、-碳环芳基-杂环芳基、-烯基杂环芳基或-烷基杂环芳基；R2代表烷基；可选地被烷基取代的碳环芳基；烯基；炔基，但三键不邻接X；-烷基芳基；-烷基杂环芳基；-烷基杂环烷基，其中杂环烷基可选地被烷基取代；-烷基碳环芳基，其中碳环芳基可选地被烷基取代；芳基；杂环芳基或H；X代表S或NR3；R3代表H或C1-4烷基。
• Inhibitors of glutaminyl cyclase
  申请人：Heiser Ulrich

  公开号：US09126987B2

  公开（公告）日：2015-09-08

  The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, wherein R1 represents heteroaryl, -carbocyclyl-heteroaryl, -alkenylheteroaryl or -alkylheteroaryl; R2 represents alkyl; carbocyclyl which may optionally be substituted by alkyl; alkenyl; alkynyl, provided a triple bond is not adjacent to X; -alkyl-aryl; -alkyl-heteroaryl; -alkyl-heterocyclyl in which heterocyclyl may optionally be substituted by alkyl; -alkyl-carbocyclyl in which carbocyclyl may optionally be substituted by alkyl; aryl; heteroaryl; or H; X represents S or NR3; R3 represents H or C1-4 alkyl.

  本发明涉及式（I）的化合物、组合物及其在疾病治疗中的用途，其中R1表示杂环芳基、-碳环芳基-杂环芳基、-烯基杂环芳基或-烷基杂环芳基；R2表示烷基；碳环芳基，可以选择性地被烷基取代；烯基；炔基，如果三键与X相邻则不适用；-烷基芳基；-烷基杂环芳基；-烷基杂环烷基，其中杂环烷基可以选择性地被烷基取代；-烷基碳环芳基，其中碳环芳基可以选择性地被烷基取代；芳基；杂环芳基；或H；X表示S或NR3；R3表示H或C1-4烷基。
• Structure–Activity Relationships of Benzimidazole-Based Glutaminyl Cyclase Inhibitors Featuring a Heteroaryl Scaffold
  作者：Daniel Ramsbeck、Mirko Buchholz、Birgit Koch、Livia Böhme、Torsten Hoffmann、Hans-Ulrich Demuth、Ulrich Heiser

  DOI：10.1021/jm4001709

  日期：2013.9.12

  Glutaminyl cyclase (hQC) has emerged as a new potential target for the treatment of Alzheimer's disease (AD). The inhibition of hQC prevents of the formation of the A beta(3(pE)-40,42) species which were shown to be of elevated neurotoidcity and are likely to act as a seeding core, leading to an accelerated formation of A beta-oligomers and fibrils. This work presents a new class of inhibitors of hQC, resulting from a pharmacophore-based screen. Hit molecules were identified, containing benzimidazole as the metal binding group connected to 1,3,4-oxadiazole as the central scaffold. The subsequent optimization resulted in benzimidazoly1-1,3,4-thiadiazoles and -1,2,3-triazoles with an inhibitory potency in the nanomolar range. Further investigation into the potential binding mode of the new compound classes combined molecular docking and site directed mutagenesis studies.
• US9126987B2
  申请人：——

  公开号：US9126987B2

  公开（公告）日：2015-09-08
• [EN] NOVEL INHIBITORS OF GLUTAMINYL CYCLASE<br/>[FR] NOUVEAUX INHIBITEURS DE GLUTAMINYLCYCLASE
  申请人：PROBIODRUG AG

  公开号：WO2008065141A1

  公开（公告）日：2008-06-05

  [EN] The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, Formula (I) wherein R¹ represents heteroaryl, -carbocyclyl-heteroaryl, -alkenylheteroaryl or -alkylheteroaryl; R² represents alkyl; carbocyclyl which may optionally be substituted by alkyl; alkenyl; alkynyl, provided a triple bond is not adjacent to X; -alkyl-aryl; -alkyl-heteroaryl; -alkyl-heterocyclyl in which heterocyclyl may optionally be substituted by alkyl; -alkyl-carbocyclyl in which carbocyclyl may optionally be substituted by alkyl; aryl; heteroaryl; or H; X represents S or NR³; R³ represents H or C_1-4 alkyl.
  [FR] La présente invention concerne des composés répondant à la formule (I), leurs combinaisons et utilisations pour une thérapie, Formule (I) dans laquelle R¹ représente un groupe hétéroaryle, -carbocyclyl-hétéroaryle, -alcénylhétéroaryle ou -alkylhétéroaryle ; R² représente un groupe alkyle ; un groupe carbocyclyle qui peut éventuellement être substitué par un groupe alkyle ; un groupe alcényle ; un groupe alcynyle, à condition qu'une liaison triple ne soit pas adjacente à X ; un groupe -alkyl-aryle ; un groupe -alkyl-hétéroaryle ; un groupe -alkyl-hétérocyclyle dans lequel le groupe hétérocyclyle peut éventuellement être substitué par un groupe alkyle ; un groupe -alkyl-carbocyclyle dans lequel le groupe carbocyclyle peut éventuellement être substitué par un groupe alkyle ; un groupe aryle ; un groupe hétéroaryle ; ou H ; X représente S ou NR³ ; R³ représente H ou un groupe alkyle en C₁ à C₄.