6-bromo-3-(hydroxymethyl)-8-methoxyimidazo<1,2-a>pyrazine | 238422-39-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡嗪类
• 英文名称: 6-bromo-3-(hydroxymethyl)-8-methoxyimidazo<1,2-a>pyrazine
• 英文别名: 6-bromo-3-(hydroxymethyl)-8-methoxyimidazo[1,2-a]pyrazine；(6-Bromo-8-methoxyimidazo[1,2-A]pyrazin-3-YL)methanol
• CAS: 238422-39-4
• 化学式: C₈H₈BrN₃O₂
• 分子量: 258.074
• InChiKey: UGMYRYRPKMELKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  59.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-bromo-3-(hydroxymethyl)-8-methoxyimidazo<1,2-a>pyrazine 在 ammonium hydroxide 作用下， 反应 2.0h， 以25%的产率得到(8-Amino-6-bromo-imidazo[1,2-a]pyrazin-3-yl)-methanol
  参考文献：
  名称：

  New imidazo[1,2-a]pyrazine derivatives with bronchodilatory and cyclic nucleotide phosphodiesterase inhibitory activities

  摘要：

  lNew imidazo[1,2-a]pyrazine derivatives have been synthesized either by direct cyclization from pyrazines or by electrophilic substitutions: The presence nf electron donating groups On position 8 greatly enhances the reactivity of the heterocycle towards such reactions on position 3 of the heterocycle. The activities of these derivatives in trachealis muscle relaxation and in inhihiting cyclic nucleotide phosphodiesterase(PDE) isoenzyme types III and IV have been assessed All compounds demonstrated higher relaxant potency than theophylline. All the derivatives were moderately potent in inhibiting the type IV isoenzyme of PDE but only those with a cyano group on position 2 were potent in inhibiting the type III isoenzyme. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00019-x
• 作为产物：
  描述：

  聚合甲醛 、 6-溴-8-甲氧基咪唑并[1,2-A]吡嗪 在 sodium acetate 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 2.0h， 以44.5%的产率得到6-bromo-3-(hydroxymethyl)-8-methoxyimidazo<1,2-a>pyrazine
  参考文献：
  名称：

  Synthesis and antibronchospastic activity of 8-alkoxy- and 8-(alkylamino)imidazo[1,2-a]pyrazines

  摘要：

  Theophylline still occupies a dominant place in asthma therapy. Unfortunatly its adverse central nervous system (CNS) stimulant effects can dramatically limit its use, and adjustments in the dosage are often needed. We have synthesized a new series of imidazo[1,2-a]pyrazine derivatives which are much more potent bronchodilators than theophylline in vivo and do not exhibit the CNS stimulatory profile. In vitro studies on isolated rat uterus and guinea pig trachea confirm the high potentialities of these derivatives. 6-Bromo-8-(methylamino)imidazo[1,2-a]pyrazine-3-carbonitrile (23) is identified as the most potent compound of the series. As in the case of theophylline, phosphodiesterase inhibition appears unlikely to be the unique mechanism of action of this series of heterocycles.

  DOI：

  10.1021/jm00096a008

文献信息

• Aza-indolizine with bridgehead nitrogen. Metalation, halogen-metal exchange and directed ortho-lithiation in the imidazo[1,2-a]pyrazine series
  作者：Olivier Vitse、Jacques Bompart、Guy Subra、Henri Viols、Roger Escale、Jean P. Chapat、Pierre A. Bonnet

  DOI：10.1016/s0040-4020(98)00287-7

  日期：1998.6

  The n-BuLi and lithium 2,2,6,6-tetramethylpiperidine (LTMP) metalation of imidazo[1,2-a]pyrazine heterocycles and subsequent quenching with electrophiles is described. Bromine atoms exhibit different behaviours towards lithiation depending on their positions (3 or 6) on the imidazo[1,2-a]pyrazine heterocycle. Halogen-metal exchange occurs readily with the bromine on position 3. On the contrary, bromine

  描述了咪唑并[1,2- a ]吡嗪杂环的n -BuLi和2,2,6,6-四甲基哌啶锂（LTMP）金属化以及随后用亲电试剂的猝灭。溴原子根据其在咪唑并[1,2- a ]吡嗪杂环上的位置（3或6）表现出不同的锂化行为。位置3上的溴很容易发生卤素金属交换。相反，位置6上的溴仅导致C-5取代的衍生物进一步产生邻位导向作用。
• Synthesis and antibronchospastic activity of 8-alkoxy- and 8-(alkylamino)imidazo[1,2-a]pyrazines
  作者：Pierre A. Bonnet、Alain Michel、Florence Laurent、Claire Sablayrolles、Eliane Rechencq、Jean C. Mani、Maurice Boucard、Jean P. Chapat

  DOI：10.1021/jm00096a008

  日期：1992.9

  Theophylline still occupies a dominant place in asthma therapy. Unfortunatly its adverse central nervous system (CNS) stimulant effects can dramatically limit its use, and adjustments in the dosage are often needed. We have synthesized a new series of imidazo[1,2-a]pyrazine derivatives which are much more potent bronchodilators than theophylline in vivo and do not exhibit the CNS stimulatory profile. In vitro studies on isolated rat uterus and guinea pig trachea confirm the high potentialities of these derivatives. 6-Bromo-8-(methylamino)imidazo[1,2-a]pyrazine-3-carbonitrile (23) is identified as the most potent compound of the series. As in the case of theophylline, phosphodiesterase inhibition appears unlikely to be the unique mechanism of action of this series of heterocycles.
• New imidazo[1,2-a]pyrazine derivatives with bronchodilatory and cyclic nucleotide phosphodiesterase inhibitory activities
  作者：Olivier Vitse、Florence Laurent、Tristan M. Pocock、Véronique Bénézech、Lahcen Zanik、Keith R.F. Elliott、Guy Subra、Karine Portet、Jacques Bompart、Jean-Pierre Chapat、Roger C. Small、Alain Michel、Pierre-Antoine Bonnet

  DOI：10.1016/s0968-0896(99)00019-x

  日期：1999.6

  lNew imidazo[1,2-a]pyrazine derivatives have been synthesized either by direct cyclization from pyrazines or by electrophilic substitutions: The presence nf electron donating groups On position 8 greatly enhances the reactivity of the heterocycle towards such reactions on position 3 of the heterocycle. The activities of these derivatives in trachealis muscle relaxation and in inhihiting cyclic nucleotide phosphodiesterase(PDE) isoenzyme types III and IV have been assessed All compounds demonstrated higher relaxant potency than theophylline. All the derivatives were moderately potent in inhibiting the type IV isoenzyme of PDE but only those with a cyano group on position 2 were potent in inhibiting the type III isoenzyme. (C) 1999 Elsevier Science Ltd. All rights reserved.