5-(benzimidazole-5(6)-yl)oxazole-4-carboxylic acid ethyl ester | 1333406-60-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5-(benzimidazole-5(6)-yl)oxazole-4-carboxylic acid ethyl ester
• 英文别名: ethyl 5-(benzimidazol-5-yl)oxazol-4-carboxylate；ethyl 5-(3H-benzimidazol-5-yl)-1,3-oxazole-4-carboxylate
• CAS: 1333406-60-2
• 化学式: C₁₃H₁₁N₃O₃
• 分子量: 257.249
• InChiKey: PURLASCEAMSNIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  81
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(benzimidazole-5(6)-yl)oxazole-4-carboxylic acid ethyl ester 在 劳森试剂 、 盐酸 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 生成 5-(2-(3,4-dimethoxyphenethyl)thiazol-5-yl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  [EN] INHIBITORS OF GLUTAMINYL CYCLASE
  [FR] NOUVEAUX INHIBITEURS

  摘要：

  公开号：

  WO2011107530A3
• 作为产物：
  描述：

  1H-苯并咪唑-5-羧酸 在 氯化亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 24.0h， 生成 5-(benzimidazole-5(6)-yl)oxazole-4-carboxylic acid ethyl ester
  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
  申请人：HEISER Ulrich

  公开号：US20110224259A1

  公开（公告）日：2011-09-15

  The invention relates to novel heterocyclic derivatives as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.

  本发明涉及新型杂环衍生物，作为谷氨酰环化酶（QC，EC 2.3.2.5）的抑制剂。QC催化N-末端谷氨酰残基的分子内环化成吡咯谷氨酸（5-氧代脯氨酰，pGlu*），释放氨，并将N-末端谷氨酸残基分子内环化成吡咯谷氨酸，释放水。
• INHIBITORS OF GLUTAMINYL CYCLASE
  申请人：Probiodrug AG

  公开号：EP2542549B1

  公开（公告）日：2016-05-11
• US9181233B2
  申请人：——

  公开号：US9181233B2

  公开（公告）日：2015-11-10
• [EN] NOVEL INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS
  申请人：PROBIODRUG AG

  公开号：WO2011107530A2

  公开（公告）日：2011-09-09

  The invention relates to novel heterocyclic derivatives as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.
• 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.