2-phenyl-8-(3-pyridoylamino)-imidazo[1,2-a]pyrazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-phenyl-8-(3-pyridoylamino)-imidazo[1,2-a]pyrazine
• 英文别名: N-(2-phenylimidazo[1,2-a]pyrazin-8-yl)pyridine-3-carboxamide
• 化学式: C₁₈H₁₃N₅O
• 分子量: 315.334
• InChiKey: WQJGDEJDXWJYFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  72.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6,8-dibromo-2-phenylimidazo[1,2-a]pyrazine 在 4-二甲氨基吡啶 、 1-hydroxybenzotriazole hydrochloride 、 palladium 10% on activated carbon 、 氨 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~120.0 ℃ 、137.9 kPa 条件下， 反应 15.0h， 生成 2-phenyl-8-(3-pyridoylamino)-imidazo[1,2-a]pyrazine
  参考文献：
  名称：

  Imidazo[1,2-a]pyrazin-8-amine core for the design of new adenosine receptor antagonists: Structural exploration to target the A3 and A2A subtypes

  摘要：

  The imidazo[1,2-a]pyrazine ring system has been chosen as a new decorable core skeleton for the design of novel adenosine receptor (AR) antagonists targeting either the human (h) A(3) or the hA(2A) receptor subtype. The N-8-(hetero)arylcarboxyamido substituted compounds 4-14 and 21-30, bearing a 6-phenyl moiety or not, respectively, show good hA(3) receptor affinity and selectivity versus the other ARs. In contrast, the 8-amino-6-(hetero)aryl substituted derivatives designed for targeting the hA(2A) receptor subtype (compounds 31-38) and also the 6-phenyl analogues 18-20 do not bind the hA(2A) AR, or show hA(1) or balanced hA(1)/hA(2A) AR affinity in the micromolar range. Molecular docking of the new hA(3) antagonists was carried out to depict their hypothetical binding mode to our refined model of the hA(3) receptor. Some derivatives were evaluated for their fluorescent potentiality and showed some fluorescent emission properties. One of the most active hA(3) antagonists herein reported, i.e. the 2,6-diphenyl-8-(3-pyridoylamino)imidazo[1,2-a]pyrazine 29, tested in a rat model of cerebral ischemia, delayed the occurrence of anoxic depolarization caused by oxygen and glucose deprivation in the hippocampus and allowed disrupted synaptic activity to recover. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.09.076

文献信息

• Imidazo[1,2-a]pyrazin-8-amine core for the design of new adenosine receptor antagonists: Structural exploration to target the A3 and A2A subtypes
  作者：Daniela Poli、Matteo Falsini、Flavia Varano、Marco Betti、Katia Varani、Fabrizio Vincenzi、Anna Maria Pugliese、Felicita Pedata、Diego Dal Ben、Ajiroghene Thomas、Ilaria Palchetti、Francesca Bettazzi、Daniela Catarzi、Vittoria Colotta

  DOI：10.1016/j.ejmech.2016.09.076

  日期：2017.1

  The imidazo[1,2-a]pyrazine ring system has been chosen as a new decorable core skeleton for the design of novel adenosine receptor (AR) antagonists targeting either the human (h) A(3) or the hA(2A) receptor subtype. The N-8-(hetero)arylcarboxyamido substituted compounds 4-14 and 21-30, bearing a 6-phenyl moiety or not, respectively, show good hA(3) receptor affinity and selectivity versus the other ARs. In contrast, the 8-amino-6-(hetero)aryl substituted derivatives designed for targeting the hA(2A) receptor subtype (compounds 31-38) and also the 6-phenyl analogues 18-20 do not bind the hA(2A) AR, or show hA(1) or balanced hA(1)/hA(2A) AR affinity in the micromolar range. Molecular docking of the new hA(3) antagonists was carried out to depict their hypothetical binding mode to our refined model of the hA(3) receptor. Some derivatives were evaluated for their fluorescent potentiality and showed some fluorescent emission properties. One of the most active hA(3) antagonists herein reported, i.e. the 2,6-diphenyl-8-(3-pyridoylamino)imidazo[1,2-a]pyrazine 29, tested in a rat model of cerebral ischemia, delayed the occurrence of anoxic depolarization caused by oxygen and glucose deprivation in the hippocampus and allowed disrupted synaptic activity to recover. (C) 2016 Elsevier Masson SAS. All rights reserved.