6-(2-aminopyrimidin-5-yl)-N-(tetrahydropyran-4-yl)-8-morpholin-4-yl-imidazo[1,2-a]pyrazine-2-carboxamide | 1252597-02-6

• 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: 6-(2-aminopyrimidin-5-yl)-N-(tetrahydropyran-4-yl)-8-morpholin-4-yl-imidazo[1,2-a]pyrazine-2-carboxamide
• 英文别名: 6-(2-aminopyrimidin-5-yl)-8-morpholin-4-yl-N-(oxan-4-yl)imidazo[1,2-a]pyrazine-2-carboxamide
• CAS: 1252597-02-6
• 化学式: C₂₀H₂₄N₈O₃
• 分子量: 424.462
• InChiKey: BTFDKNWRSWJHKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 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 6-(2-aminopyrimidin-5-yl)-N-(tetrahydropyran-4-yl)-8-morpholin-4-yl-imidazo[1,2-a]pyrazine-2-carboxamide
  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 FOR USE AS KINASE INHIBITORS
  申请人：Pastor Fernández Joaquin

  公开号：US20120083492A1

  公开（公告）日：2012-04-05

  There is provided compounds of formula (I), wherein R 1 , R 2 , R 3 , R 4 and R 5 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

  提供了式(I)的化合物，其中R1、R2、R3、R4和R5在描述中有给定的含义，以及它们的药用可接受的酯、酰胺、溶剂合物或盐，这些化合物在治疗需要或期望抑制蛋白质或脂质激酶（例如PI3-K和/或mTOR）的疾病方面非常有用，特别是在治疗癌症或增生性疾病方面。
• Use of P13K Inhibitors for the Treatment of Obesity, Steatosis and ageing
  申请人：Serrano Marugan Manuel

  公开号：US09993554B2

  公开（公告）日：2018-06-12

  The first aspect of the invention relates to a phosphoinositide 3-kinase inhibitor for use in the treatment or prevention of a disease or condition associated with the expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgd1α) and/or uncoupling protein 1 (Thermogenin/Ucp1) in brown adipocytes. The disease or condition may be positive energy imbalance-associated, for example, obesity, an obesity-associated disease or condition, steatosis and biological aging (performance aging). Another aspect of the invention provides the use of a phosphoinositide 3-kinase inhibitor for promoting weight loss in an individual.

  该发明的第一个方面涉及一种磷脂酰肌醇3-激酶抑制剂，用于治疗或预防与棕色脂肪细胞中过氧化物酶体增殖物激活受体γ共激活因子1-α（Pgd1α）和/或解偶联蛋白1（热原蛋白/Ucp1）表达相关的疾病或病况。该疾病或病况可能与正能量失衡相关，例如肥胖、肥胖相关疾病或病况、脂肪肝和生物老化（性能老化）。该发明的另一个方面提供了使用磷脂酰肌醇3-激酶抑制剂促进个体体重减轻的方法。
• 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
• USE OF PI3K INHIBITORS FOR THE TREATMENT OF OBESITY, STEATOSIS AND AGEING
  申请人：Fundación Centro Nacional de Investigaciones Oncológicas Carlos III

  公开号：EP2629771B1

  公开（公告）日：2018-08-08
• US8778935B2
  申请人：——

  公开号：US8778935B2

  公开（公告）日：2014-07-15