5-[5-Chloro-2-(4-methanesulfonyl-piperazin-1-ylmethyl)-8-morpholin-4-yl-imidazo[1,2-a]pyrazin-6-yl]-pyrimidin-2-ylamin | 1252595-56-4

• 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: 5-[5-Chloro-2-(4-methanesulfonyl-piperazin-1-ylmethyl)-8-morpholin-4-yl-imidazo[1,2-a]pyrazin-6-yl]-pyrimidin-2-ylamin
• 英文别名: 5-[5-chloro-2-[(4-methylsulfonylpiperazin-1-yl)methyl]-8-morpholin-4-ylimidazo[1,2-a]pyrazin-6-yl]pyrimidin-2-amine
• CAS: 1252595-56-4
• 化学式: C₂₀H₂₆ClN₉O₃S
• 分子量: 508.004
• InChiKey: LOCCAHWMIIHOFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  144
• 氢给体数：
  1
• 氢受体数：
  11

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 、 N-氯代丁二酰亚胺 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 85.0h， 生成 5-[5-Chloro-2-(4-methanesulfonyl-piperazin-1-ylmethyl)-8-morpholin-4-yl-imidazo[1,2-a]pyrazin-6-yl]-pyrimidin-2-ylamin
  参考文献：
  名称：

  Use of P13K Inhibitors for the Treatment of Obesity, Steatosis and ageing

  摘要：

  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。

  公开号：

  US09993554B2

文献信息

• Identification of novel PI3K inhibitors through a scaffold hopping strategy
  作者：Sonia Martínez González、Ana Isabel Hernández、Rosa María Álvarez、Antonio Rodríguez、Francisco Ramos-Lima、James R. Bischoff、María Isabel Albarrán、Antonio Cebriá、Elena Hernández-Encinas、Jennifer García-Arocha、David Cebrián、Carmen Blanco-Aparicio、Joaquín Pastor

  DOI：10.1016/j.bmcl.2017.09.059

  日期：2017.11

  scaffold hopping strategy, including intellectual property availability assessment, was successfully applied for the discovery of novel PI3K inhibitors. Compounds were designed based on the chemical structure of the lead compound ETP-46321, a potent PI3K inhibitor, previously reported by our group. The new generated compounds showed good in vitro potency and selectivity, proved to inhibit potently the

  脚手架跳策略，包括知识产权可用性评估，已成功应用于新型PI3K抑制剂的发现。根据先导化合物E​​TP-46321（一种有效的PI3K抑制剂）的化学结构设计化合物，之前我们的研究小组已对此进行了报道。新产生的化合物显示出良好的体外效能和选择性，被证明可有效抑制细胞中AKT Ser473的磷酸化，并被证明具有口服生物利用度，因此成为ETP-46321的潜在后备候选药物。
• 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 PI3K inibitors for the treatment of obesity
  申请人：Centro Nacional de Investigaciones Oncológicas (CNIO)

  公开号：EP2444084A1

  公开（公告）日：2012-04-25

  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 (Pgc1α) 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，用于治疗或预防与褐色脂肪细胞中过氧化物酶体增殖激活受体γ共激活因子1-α（Pgc1α）和/或解偶联蛋白1（Thermogenin/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、与肥胖相关的疾病或病况、脂肪肝和生物老化（表现老化）。该发明的另一个方面提供了利用磷脂酰肌醇3-激酶抑制剂促进个体体重减轻的用途。
• Identification of ETP-46321, a potent and orally bioavailable PI3K α, δ inhibitor
  作者：Sonia Martínez González、Ana Isabel Hernández、Carmen Varela、Sonsoles Rodríguez-Arístegui、Milagros Lorenzo、Antonio Rodríguez、Virginia Rivero、José Ignacio Martín、Carl Gustav Saluste、Francisco Ramos-Lima、Elena Cendón、David Cebrián、Enara Aguirre、Elena Gomez-Casero、Maribel Albarrán、Patricia Alfonso、Beatriz García-Serelde、Julen Oyarzabal、Obdulia Rabal、Francisca Mulero、Teresa Gonzalez-Granda、Wolfgang Link、Jesús Fominaya、Mariano Barbacid、James R. Bischoff、Pilar Pizcueta、Joaquín Pastor

  DOI：10.1016/j.bmcl.2012.03.090

  日期：2012.5

  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.
• 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