5-(bromomethyl)pyrazine-2-carboxylic acid | 782434-80-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(bromomethyl)pyrazine-2-carboxylic acid
• 英文别名: 5-(bromomethyl)-2-Pyrazinecarboxylic acid
• CAS: 782434-80-4
• 化学式: C₆H₅BrN₂O₂
• 分子量: 217.022
• InChiKey: MPMJIWLVFNDGKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(bromomethyl)pyrazine-2-carboxylic acid 在 水 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 64.25h， 生成 5-[(tert-butoxycarbonyl-cyclopropyl-amino)methyl]pyrazine-2-carboxylic acid
  参考文献：
  名称：

  Discovery of Further Pyrrolidine trans-Lactams as Inhibitors of Human Neutrophil Elastase (HNE) with Potential as Development Candidates and the Crystal Structure of HNE Complexed with an Inhibitor (GW475151)

  摘要：

  Described herein is a modern approach to the rapid preparation and evaluation of compounds as potential back-up drug candidates. GW311616A, 1, a derivative of pyrrolidine trans-lactams, has previously been described as a potent, orally active inhibitor of human neutrophil elastase (HNE) for the treatment of respiratory disease. These properties made it a suitable candidate for development. Described here is the discovery of three further derivatives of pyrrolidine trans-lactams, which fulfill the criteria required for back-up candidates 28, 29, and 32. These include increased activity in inhibiting HNE in human whole blood (HWB) and comparable pharmacokinetic properties, in particular clearance, in two species. To provide a rapid assessment of clearance, cassette dosing in dog was used. Modern array techniques, including the synthesis of mixtures, were used to synthesize compounds rapidly. Having selected three potential compounds as back-up candidates, they were prepared as single enantiomers and profiled in in vitro and in vivo assays and evaluated pharmacokinetically in rat and dog. These compounds are highly potent and selective HNE inhibitors, with a prolonged pharmacodynamic action. Pharmacokinetically, these compounds are comparable with I while they are more potent in HWB. Compound 28, however, has a higher clearance. One of these compounds, 32, was cocrystallized with HNE, and features of this structure are described and compared with the cocrystal structure of 1 in porcine pancreatic elastase.

  DOI：

  10.1021/jm020881f
• 作为产物：
  描述：

  5-(溴甲基)吡嗪-2-羧酸甲酯 在 氢氧化钾 作用下， 以 水 为溶剂， 反应 2.0h， 以68%的产率得到5-(bromomethyl)pyrazine-2-carboxylic acid
  参考文献：
  名称：

  Discovery of Further Pyrrolidine trans-Lactams as Inhibitors of Human Neutrophil Elastase (HNE) with Potential as Development Candidates and the Crystal Structure of HNE Complexed with an Inhibitor (GW475151)

  摘要：

  Described herein is a modern approach to the rapid preparation and evaluation of compounds as potential back-up drug candidates. GW311616A, 1, a derivative of pyrrolidine trans-lactams, has previously been described as a potent, orally active inhibitor of human neutrophil elastase (HNE) for the treatment of respiratory disease. These properties made it a suitable candidate for development. Described here is the discovery of three further derivatives of pyrrolidine trans-lactams, which fulfill the criteria required for back-up candidates 28, 29, and 32. These include increased activity in inhibiting HNE in human whole blood (HWB) and comparable pharmacokinetic properties, in particular clearance, in two species. To provide a rapid assessment of clearance, cassette dosing in dog was used. Modern array techniques, including the synthesis of mixtures, were used to synthesize compounds rapidly. Having selected three potential compounds as back-up candidates, they were prepared as single enantiomers and profiled in in vitro and in vivo assays and evaluated pharmacokinetically in rat and dog. These compounds are highly potent and selective HNE inhibitors, with a prolonged pharmacodynamic action. Pharmacokinetically, these compounds are comparable with I while they are more potent in HWB. Compound 28, however, has a higher clearance. One of these compounds, 32, was cocrystallized with HNE, and features of this structure are described and compared with the cocrystal structure of 1 in porcine pancreatic elastase.

  DOI：

  10.1021/jm020881f
• 作为试剂：
  描述：

  5-(溴甲基)吡嗪-2-羧酸甲酯 、 potassium trimethylsilonate 、 盐酸 在 乙酸乙酯 、 Sodium sulfate-III 、 silica gel 、 5-(bromomethyl)pyrazine-2-carboxylic acid 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.75h， 以to afford the title compound 5-(bromomethyl)pyrazine-2-carboxylic acid (0.174 g, 37% yield) as a yellow solid的产率得到5-(bromomethyl)pyrazine-2-carboxylic acid
  参考文献：
  名称：

  N-ARYLMETHYL SULFONAMIDE NEGATIVE MODULATORS OF NR2A

  摘要：

  本发明公开了选择性负调节含有NR2A亚基的NMDA受体的化合物、包含该化合物的制药组合物以及使用该化合物治疗疾病的方法。

  公开号：

  US20150141433A1

文献信息

• [EN] N-ARYLMETHYL SULFONAMIDE NEGATIVE MODULATORS OF NR2A<br/>[FR] MODULATEURS NÉGATIFS N-ARYLMÉTHYL SULFONAMIDE DE NR2A
  申请人：MNEMOSYNE PHARMACEUTICALS INC

  公开号：WO2015048503A3

  公开（公告）日：2015-11-19
• Incorporation of Heterocycles into the Backbone of Peptoids to Generate Diverse Peptoid-Inspired One Bead One Compound Libraries
  作者：Animesh Aditya、Thomas Kodadek

  DOI：10.1021/co200195t

  日期：2012.3.12

  Combinatorial libraries of peptoids (oligo-N-substituted glycines) have proven to be useful sources of protein ligands. Each unit of the peptoid oligomer is derived from 2-haloacetic acid and a primary amine. To increase the chemical diversity available in peptoid libraries, we demonstrate here that heterocyclic halomethyl carboxylic acids can be employed as backbone building blocks in the synthesis of peptoid-based oligomers. Optimized conditions are reported that allow the creation of large, high quality combinatorial libraries containing these units.
• US9963434B2
  申请人：——

  公开号：US9963434B2

  公开（公告）日：2018-05-08