Ethyl 8-chloro-6-iodoimidazo[1,2-a]pyrazine-2-carboxylate | 1252598-18-7

• 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: Ethyl 8-chloro-6-iodoimidazo[1,2-a]pyrazine-2-carboxylate
• CAS: 1252598-18-7
• 化学式: C₉H₇ClIN₃O₂
• 分子量: 351.531
• InChiKey: QEQSQGKFSCULFZ-UHFFFAOYSA-N

物化性质

• 密度：
  2.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 8-chloro-6-iodoimidazo[1,2-a]pyrazine-2-carboxylate 在 manganese(IV) oxide 、 N-溴代丁二酰亚胺(NBS) 、 二异丁基氢化铝 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 生成 3-Bromo-6-iodo-8-morpholin-4-ylimidazo[1,2-a]pyrazine-2-carbaldehyde
  参考文献：
  名称：

  Identification of ETP-46321, a potent and orally bioavailable PI3K α, δ inhibitor

  摘要：

  Phosphoinositide-3-kinase (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 optimization of imidazo [1,2-a] pyrazines, which allow us to identify compound 14 (ETP-46321), with potent biochemical and cellular activity and good pharmacokinetic properties (PK) after oral dosing. ETP-46321 PK/PD studies showed time dependent downregulation of AKT(Ser473) phosphorylation, which correlates with compound levels in tumor tissue and demonstrating to be efficacious in a GEMM mouse tumor model driven by a K-Ras(G12V) oncogenic mutation. Treatment with ETP-46321 resulted in significant tumor growth inhibition. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.090
• 作为产物：
  描述：

  3-溴丙酮酸乙酯 、 3-氯-5-碘吡嗪-2-胺 在 sodium iodide 作用下， 以 异丙醇 为溶剂， 以78%的产率得到Ethyl 8-chloro-6-iodoimidazo[1,2-a]pyrazine-2-carboxylate
  参考文献：
  名称：

  Identification of ETP-46321, a potent and orally bioavailable PI3K α, δ inhibitor

  摘要：

  Phosphoinositide-3-kinase (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 optimization of imidazo [1,2-a] pyrazines, which allow us to identify compound 14 (ETP-46321), with potent biochemical and cellular activity and good pharmacokinetic properties (PK) after oral dosing. ETP-46321 PK/PD studies showed time dependent downregulation of AKT(Ser473) phosphorylation, which correlates with compound levels in tumor tissue and demonstrating to be efficacious in a GEMM mouse tumor model driven by a K-Ras(G12V) oncogenic mutation. Treatment with ETP-46321 resulted in significant tumor growth inhibition. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.090