4-羟基-1H-苯并咪唑-2-羧酸 | 910026-61-8

• 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: 4-羟基-1H-苯并咪唑-2-羧酸
• 英文名称: 7-hydroxy-1H-benzimidazole-2-carboxylic acid
• 英文别名: 4-hydroxy-1H-benzimidazole-2-carboxylic acid
• CAS: 910026-61-8
• 化学式: C₈H₆N₂O₃
• mdl: MFCD18807811
• 分子量: 178.147
• InChiKey: HIQPMJKWRGCTOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  86.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-羟基-1H-苯并咪唑-2-羧酸 、 4-苄基哌啶 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (4-benzylpiperidin-1-yl)-(7-hydroxy-1H-benzimidazol-2-yl)-methanone
  参考文献：
  名称：

  Selective NR1/2B N-Methyl-d-aspartate Receptor Antagonists among Indole-2-carboxamides and Benzimidazole-2-carboxamides

  摘要：

  (4-苄基哌啶-1-基)-(6-羟基-1H-吲哚-2-基)-甲酮(6a)是从(E)-1-(4-苄基哌啶-1-基)-3-(4-羟基苯基)丙烯酮(5)中鉴定出的一种强效的NMDA受体NR2B亚基选择性拮抗剂。为了建立结构-活性关系(SAR)并尝试改善先导化合物的ADME性质，制备并测试了一系列化合物。多种衍生物在结合和功能性测定中均显示出低纳摩尔的活性。在环磷酰胺诱导的小鼠痛觉过敏模型中，6a和(4-苄基哌啶-1-基)-[5(6)-羟基-1H-联吡啶-2-基]-甲酮(60a)在口服给药后与Besonprodil(2)具有相同的活性。基于一系列吲哚-和联吡啶-2-羧酰胺的结合数据，开发了一种CoMSIA模型。

  DOI：

  10.1021/jm060420k
• 作为产物：
  描述：

  N-(2-Benzyloxy-6-nitro-phenyl)-N'-butyl-oxalamide 在 palladium on activated charcoal 氢溴酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 48.17h， 生成 4-羟基-1H-苯并咪唑-2-羧酸
  参考文献：
  名称：

  Benzimidazole-2-carboxamides as novel NR2B selective NMDA receptor antagonists

  摘要：

  A novel series of benzimidazole-2-carboxamide derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of some structural elements, like H-bond donor groups placed on the benzimidazole skeleton and the substitution pattern of the piperidine ring, on the biological activity was studied. Compound 6a showed excellent analgetic activity in the mouse formalin test following po administration. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.002

文献信息

• [EN] COMPOUNDS INHIBITORS OF ENZYME LACTATE DEHYDROGENASE (LDH) AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS D'ENZYME LACTATE DÉSHYDROGÉNASE (LDH) ET COMPOSITIONS PHARMACEUTIQUES CONTENANT CES COMPOSÉS
  申请人：UNIV PISA

  公开号：WO2011054525A1

  公开（公告）日：2011-05-12

  The present invention concerns compounds, some of which are novel, and their pharmaceutical applications. The compounds of the invention inhibit the enzyme lactate dehydrogenase (LDH) involved both in the metabolic process of hypoxic tumour cells, and in the process used by parasitic protozoa that cause malaria to obtain most of the energy they need.

  这项发明涉及化合物，其中一些是新颖的，以及它们的药用应用。该发明的化合物抑制乳酸脱氢酶（LDH）酶，该酶参与低氧肿瘤细胞的代谢过程，以及疟疾引起的寄生原虫利用获取所需大部分能量的过程。
• COMPOUNDS INHIBITORS OF ENZYME LACTATE DEHYDROGENASE (LDH) AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS
  申请人：Universita Di Pisa

  公开号：EP2499114A1

  公开（公告）日：2012-09-19
• Selective NR1/2B <i>N</i>-Methyl-<scp>d</scp>-aspartate Receptor Antagonists among Indole-2-carboxamides and Benzimidazole-2-carboxamides
  作者：István Borza、Éva Bozó、Gizella Barta-Szalai、Csilla Kiss、Gábor Tárkányi、Ádám Demeter、Tamás Gáti、Viktor Háda、Sándor Kolok、Anikó Gere、László Fodor、József Nagy、Kornél Galgóczy、Ildikó Magdó、Béla Ágai、József Fetter、Ferenc Bertha、György M. Keserü、Csilla Horváth、Sándor Farkas、István Greiner、György Domány

  DOI：10.1021/jm060420k

  日期：2007.3.1

  (4-Benzylpiperidine-1-yl)-(6-hydroxy-1H-indole-2-yl)-methanone (6a) derived from (E)-1-(4-benzylpiperidin-1-yl)-3-(4-hydroxy-phenyl)-propenone (5) was identified as a potent NR2B subunit-selective antagonist of the NMDA receptor. To establish the structure-activity relationship (SAR) and to attempt the improvement of the ADME properties of the lead, a series of compounds were prepared and tested. Several derivatives showed low nanomolar activity both in the binding and in the functional assay. In a formalin-induced hyperalgesia model in mice, 6a and (4-benzylpiperidine-1-yl)-[5(6)-hydroxy-1H-benzimidazol-2-yl]-methanone (60a) were as active as besonprodil (2) after oral administration. A CoMSIA model was developed based on binding data of a series of indole- and benzimidazole-2-carboxamides.

  (4-苄基哌啶-1-基)-(6-羟基-1H-吲哚-2-基)-甲酮(6a)是从(E)-1-(4-苄基哌啶-1-基)-3-(4-羟基苯基)丙烯酮(5)中鉴定出的一种强效的NMDA受体NR2B亚基选择性拮抗剂。为了建立结构-活性关系(SAR)并尝试改善先导化合物的ADME性质，制备并测试了一系列化合物。多种衍生物在结合和功能性测定中均显示出低纳摩尔的活性。在环磷酰胺诱导的小鼠痛觉过敏模型中，6a和(4-苄基哌啶-1-基)-[5(6)-羟基-1H-联吡啶-2-基]-甲酮(60a)在口服给药后与Besonprodil(2)具有相同的活性。基于一系列吲哚-和联吡啶-2-羧酰胺的结合数据，开发了一种CoMSIA模型。
• Benzimidazole-2-carboxamides as novel NR2B selective NMDA receptor antagonists
  作者：István Borza、Sándor Kolok、Anikó Gere、József Nagy、László Fodor、Kornél Galgóczy、József Fetter、Ferenc Bertha、Béla Ágai、Csilla Horváth、Sándor Farkas、György Domány

  DOI：10.1016/j.bmcl.2006.06.002

  日期：2006.9

  A novel series of benzimidazole-2-carboxamide derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of some structural elements, like H-bond donor groups placed on the benzimidazole skeleton and the substitution pattern of the piperidine ring, on the biological activity was studied. Compound 6a showed excellent analgetic activity in the mouse formalin test following po administration. (c) 2006 Elsevier Ltd. All rights reserved.