Imidazo[1,2-a]pyrazine, 6-methyl-8-(methylsulfonyl)-3-[1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazol-4-yl]- | 1094070-49-1

• 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: Imidazo[1,2-a]pyrazine, 6-methyl-8-(methylsulfonyl)-3-[1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazol-4-yl]-
• 英文别名: trimethyl-[2-[[4-(6-methyl-8-methylsulfonylimidazo[1,2-a]pyrazin-3-yl)pyrazol-1-yl]methoxy]ethyl]silane
• CAS: 1094070-49-1
• 化学式: C₁₇H₂₅N₅O₃SSi
• 分子量: 407.569
• InChiKey: GFDGUBWLQCCAFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.62
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  99.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Imidazo[1,2-a]pyrazine, 6-methyl-8-(methylsulfonyl)-3-[1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazol-4-yl]- 在 sodium hydroxide 、 水 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.17h， 生成 5-[[6-Methyl-3-[1-(2-trimethylsilylethoxymethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]thiophene-3-carboxylic acid
  参考文献：
  名称：

  WO2008/156614

  摘要：

  公开号：
• 作为产物：
  描述：

  6-Methyl-8-(methylthio)-3-[1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazine 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 Imidazo[1,2-a]pyrazine, 6-methyl-8-(methylsulfonyl)-3-[1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazol-4-yl]-
  参考文献：
  名称：

  WO2008/156614

  摘要：

  公开号：

文献信息

• Bioisosteric approach to the discovery of imidazo[1,2-a]pyrazines as potent Aurora kinase inhibitors
  作者：Zhaoyang Meng、Bheemashankar A. Kulkarni、Angela D. Kerekes、Amit K. Mandal、Sara J. Esposite、David B. Belanger、Panduranga Adulla Reddy、Andrea D. Basso、Seema Tevar、Kimberly Gray、Jennifer Jones、Elizabeth B. Smith、Ronald J. Doll、M. Arshad Siddiqui

  DOI：10.1016/j.bmcl.2010.10.008

  日期：2011.1

  Our continued effort toward the development of the imidazo[1,2-a] pyrazine scaffold as Aurora kinase inhibitors is described. Bioisosteric approach was applied to optimize the 8-position of the core. Several new potent Aurora A/B dual inhibitors, such as 25k and 25l, were identified. (C) 2010 Elsevier Ltd. All rights reserved.
• Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors
  作者：David B. Belanger、Michael J. Williams、Patrick J. Curran、Amit K. Mandal、Zhaoyang Meng、Matthew P. Rainka、Tao Yu、Neng-Yang Shih、M. Arshad Siddiqui、Ming Liu、Seema Tevar、Suining Lee、Lianzhu Liang、Kimberly Gray、Bohdan Yaremko、Jennifer Jones、Elizabeth B. Smith、Dan B. Prelusky、Andrea D. Basso

  DOI：10.1016/j.bmcl.2010.08.140

  日期：2010.11

  We report a series of potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Optimization of the solvent accessible 8-position led to improvements in both oral bioavailability and off-target kinase inhibition. Compound 25 demonstrates anti-tumor activity in an A2780 ovarian tumor xenograft model. (C) 2010 Elsevier Ltd. All rights reserved.
• Discovery of a Potent, Injectable Inhibitor of Aurora Kinases Based on the Imidazo-[1,2-<i>a</i>]-Pyrazine Core
  作者：Tao Yu、Jayaram R. Tagat、Angela D. Kerekes、Ronald J. Doll、Yonglian Zhang、Yushi Xiao、Sara Esposite、David B. Belanger、Patrick J. Curran、Amit K. Mandal、M. Arshad Siddiqui、Neng-Yang Shih、Andrea D. Basso、Ming Liu、Kimberly Gray、Seema Tevar、Jennifer Jones、Suining Lee、Lianzhu Liang、Samad Ponery、Elizabeth B. Smith、Alan Hruza、Johannes Voigt、Lata Ramanathan、Winifred Prosise、Mengwei Hu

  DOI：10.1021/ml100063w

  日期：2010.8.12

  The imidazo-[1,2-a]-pyrazine (1) is a dual inhibitor of Aurora kinases A and B with modest cell potency (IC50 = 250 nM) and low solubility (5 mu M). Lead optimization guided by the binding mode led to the acyclic amino alcohol 12k (SCH 1473759), which is a picomolar inhibitor of Aurora kinases (TdF K-d Aur A = 0.02 nM and Aur B = 0.03 nM) with improved cell potency (phos-HH3 inhibition IC50 = 25 nM) and intrinsic aqueous solubility (11.4 mM). It also demonstrated efficacy and target engagement in human tumor xenograft mouse models.
• WO2008/156614
  申请人：——

  公开号：——

  公开（公告）日：——