3-methyl-1-[[5-[[6-methyl-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]amino]-1,2-thiazol-3-yl]methyl]pyridin-2-one | 1094205-55-6

• 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: 3-methyl-1-[[5-[[6-methyl-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]amino]-1,2-thiazol-3-yl]methyl]pyridin-2-one
• CAS: 1094205-55-6
• 化学式: C₂₀H₁₈N₈OS
• 分子量: 418.482
• InChiKey: PDEYSICBOCYERS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(bromomethyl)-N-(6-methyl-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)isothiazol-5-amine 在 盐酸 、 sodium hydride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-methyl-1-[[5-[[6-methyl-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]amino]-1,2-thiazol-3-yl]methyl]pyridin-2-one
  参考文献：
  名称：

  Discovery of a highly potent orally bioavailable imidazo-[1, 2- a ]pyrazine Aurora inhibitor

  摘要：

  Imidazo-[1, 2-a]pyrazine 1 is a potent inhibitor of Aurora A and B kinase in vitro and is effective in in vivo tumor models, but has poor oral bioavailbility and is unsuitable for oral dosing. We describe herein our effort to improve oral exposure in this class, resulting ultimately in the identification of a potent Aurora inhibitor 16, which exhibited good drug exposure levels across species upon oral dosing, and showed excellent in vivo efficacy in a mouse xenograft tumor model when dosed orally. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.02.037

文献信息

• [EN] IMIDAZOPYRAZINES AS PROTEIN KINASE INHIBITORS<br/>[FR] IMIDAZOPYRAZINES COMME INHIBITEURS DE LA PROTÉINE KINASE
  申请人：SCHERING CORP

  公开号：WO2008156614A2

  公开（公告）日：2008-12-24

  [EN] In its many embodiments, the present invention provides a novel class of imidazopyrazine compounds as inhibitors of protein and/or Aurora kinases, methods of preparing such compounds, pharmaceutical compositions including one or more such compounds, methods of preparing pharmaceutical formulations including one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the protein or Aurora kinases using such compounds or pharmaceutical compositions.
  [FR] Dans ses nombreux modes de réalisation, la présente invention porte sur une nouvelle classe de composés imidazopyrazine comme inhibiteurs de protéine et/ou d'Aurora kinases, sur des procédés de préparation de ces composés, sur des compositions pharmaceutiques comprenant un ou plusieurs de ces composés, sur des procédés de préparation de formulations pharmaceutiques comprenant un ou plusieurs de ces composés et sur des procédés de traitement, de prévention, d'inhibition ou d'amélioration d'une ou plusieurs maladies associées aux protéines ou Aurora kinases à l'aide de ces composés et de ces compositions pharmaceutiques.
• Discovery of a highly potent orally bioavailable imidazo-[1, 2- a ]pyrazine Aurora inhibitor
  作者：Tao Yu、Yonglian Zhang、Angela D. Kerekes、Jayaram R. Tagat、Ronald J. Doll、Yushi Xiao、Sara Esposite、Alan Hruza、David B. Belanger、Matthew Voss、Matthew P. Rainka、Andrea Basso、Ming Liu、Lianzhu Liang、Ning Sui、Daniel Prelusky、Diane Rindgen、Likang Zhang

  DOI：10.1016/j.bmcl.2018.02.037

  日期：2018.5

  Imidazo-[1, 2-a]pyrazine 1 is a potent inhibitor of Aurora A and B kinase in vitro and is effective in in vivo tumor models, but has poor oral bioavailbility and is unsuitable for oral dosing. We describe herein our effort to improve oral exposure in this class, resulting ultimately in the identification of a potent Aurora inhibitor 16, which exhibited good drug exposure levels across species upon oral dosing, and showed excellent in vivo efficacy in a mouse xenograft tumor model when dosed orally. (C) 2018 Elsevier Ltd. All rights reserved.