ETP-46992 | 1252597-38-8

• 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: ETP-46992
• 英文别名: 6-(2-aminopyrimidin-5-yl)-N-(2-methoxyethyl)-3-methyl-8-morpholin-4-ylimidazo[1,2-a]pyrazine-2-carboxamide
• CAS: 1252597-38-8
• 化学式: C₁₉H₂₄N₈O₃
• 分子量: 412.451
• InChiKey: SACVGFNKAAPQIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氨基-5-溴-3-吗啉-4-基吡嗪 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 三甲基铝 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 反应 36.0h， 生成 ETP-46992
  参考文献：
  名称：

  Rapid identification of ETP-46992, orally bioavailable PI3K inhibitor, selective versus mTOR

  摘要：

  Phosphoinositide-3-kinases (PI3K) are a family of lipid kinases mediating numerous cell processes such as proliferation, migration and differentiation. PI3K is an important target for cancer therapeutics due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein, we describe the rapid identification of ETP-46992, within 2-aminocarbonyl imidazo [1,2-a] pyrazine series, with suitable pharmacokinetic (PK) properties that allows the establishment of mechanism of action and efficacy in vivo studies. ETP-46992 showed tumor growth inhibition in a GEMM mouse tumor model driven by a K-Ras(G12V) oncogenic mutation and in tumor xenograft models with PI3K pathway deregulated (BT474). (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.093

文献信息

• IMIDAZOPYRAZINES AS INHIBITORS OF PROTEIN KINASES
  申请人：Centro Nacional de Investigaciones Oncológicas (CNIO)

  公开号：EP2419429B1

  公开（公告）日：2014-03-26
• Rapid identification of ETP-46992, orally bioavailable PI3K inhibitor, selective versus mTOR
  作者：Sonia Martínez González、Ana Isabel Hernández、Carmen Varela、Milagros Lorenzo、Francisco Ramos-Lima、Elena Cendón、David Cebrián、Enara Aguirre、Elena Gomez-Casero、M.I. Albarrán、Patricia Alfonso、Beatriz García-Serelde、Genoveva Mateos、Julen Oyarzabal、Obdulia Rabal、Francisca Mulero、Teresa Gonzalez-Granda、Wolfgang Link、Jesús Fominaya、Mariano Barbacid、James R. Bischoff、Pilar Pizcueta、Carmen Blanco-Aparicio、Joaquín Pastor

  DOI：10.1016/j.bmcl.2012.06.093

  日期：2012.8

  Phosphoinositide-3-kinases (PI3K) are a family of lipid kinases mediating numerous cell processes such as proliferation, migration and differentiation. PI3K is an important target for cancer therapeutics due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein, we describe the rapid identification of ETP-46992, within 2-aminocarbonyl imidazo [1,2-a] pyrazine series, with suitable pharmacokinetic (PK) properties that allows the establishment of mechanism of action and efficacy in vivo studies. ETP-46992 showed tumor growth inhibition in a GEMM mouse tumor model driven by a K-Ras(G12V) oncogenic mutation and in tumor xenograft models with PI3K pathway deregulated (BT474). (c) 2012 Elsevier Ltd. All rights reserved.