5-dibromomethyl-pyrazine-2-carboxylic acid methyl ester | 866327-72-2

• 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-dibromomethyl-pyrazine-2-carboxylic acid methyl ester
• 英文别名: Methyl 5-(dibromomethyl)pyrazine-2-carboxylate
• CAS: 866327-72-2
• 化学式: C₇H₆Br₂N₂O₂
• mdl: MFCD25968076
• 分子量: 309.945
• InChiKey: VLUNGFXWFUJWMG-UHFFFAOYSA-N

物化性质

• 沸点：
  355.7±37.0 °C(Predicted)
• 密度：
  1.971±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  5-dibromomethyl-pyrazine-2-carboxylic acid methyl ester 、 乙醇 在 silver nitrate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.25h， 以to yield the title compound (1.36 g)的产率得到5-甲酰基吡嗪-2-羧酸甲酯
  参考文献：
  名称：

  Pyridine compounds as histamine H3 modulators

  摘要：

  某些非咪唑杂环化合物是组胺H3受体调节剂，用于治疗组胺H3受体介导的疾病。

  公开号：

  US07423147B2
• 作为产物：
  描述：

  5-甲基吡嗪-2-羧酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 18.0h， 以31%的产率得到5-dibromomethyl-pyrazine-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Non-Imidazole heterocyclic compounds

  摘要：

  某些非咪唑杂环化合物是组胺H3调节剂，可用于治疗组胺H3受体介导的疾病。

  公开号：

  US20050222151A1

文献信息

• Isoxazole Compounds as Histamine H3 modulators
  申请人：Carruthers Nicholas I.

  公开号：US20100022539A1

  公开（公告）日：2010-01-28

  Certain isoxazole compounds are histamine H 3 modulators useful in the treatment of histamine H 3 receptor mediated diseases.

  某些异唑啉化合物是组胺H3调节剂，可用于治疗组胺H3受体介导的疾病。
• NON-IMIDAZOLE HETEROCYCLIC COMPOUNDS
  申请人：Carruthers Nicholas I.

  公开号：US20080306066A1

  公开（公告）日：2008-12-11

  Certain non-imidazole heterocyclic compounds are histamine H 3 modulators useful in the treatment of histamine H 3 receptor mediated diseases.

  某些非咪唑杂环化合物是组胺H3调节剂，可用于治疗组胺H3受体介导的疾病。
• Isoxazole compounds as histamine H3 modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US07947718B2

  公开（公告）日：2011-05-24

  Certain isoxazole compounds are histamine H3 modulators useful in the treatment of histamine H3 receptor mediated diseases.

  某些异唑啉类化合物是组胺H3调节剂，在治疗组胺H3受体介导的疾病中有用。
• Discovery of Further Pyrrolidine <i>trans</i>-Lactams as Inhibitors of Human Neutrophil Elastase (HNE) with Potential as Development Candidates and the Crystal Structure of HNE Complexed with an Inhibitor (GW475151)
  作者：Simon J. F. Macdonald、Michael D. Dowle、Lee A. Harrison、Geoffrey D. E. Clarke、Graham G. A. Inglis、Martin R. Johnson、Pritom Shah、Robin A. Smith、Augustin Amour、Gill Fleetwood、Davina C. Humphreys、Christopher R. Molloy、Mary Dixon、Rosalind E. Godward、Alan J. Wonacott、Onkar M. P. Singh、Simon T. Hodgson、George W. Hardy

  DOI：10.1021/jm020881f

  日期：2002.8.1

  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.
• NON-IMIDAZOLE HETEROCYCLIC COMPOUNDS AS HISTAMINE H3-RECEPTOR LIGANDS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1761496A2

  公开（公告）日：2007-03-14