(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone | 1033733-75-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (3-(2-(2-aminopyrimidin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone
• 英文别名: [3-[2-(2-aminopyrimidin-5-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]phenyl]-(4-methylpiperazin-1-yl)methanone
• CAS: 1033733-75-3
• 化学式: C₂₆H₂₈N₈O₂S
• 分子量: 516.627
• InChiKey: AQTJNMUVTLTNOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  142
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-氨基嘧啶-5-硼酸频哪酯 、 (3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium acetate 作用下， 以 水 、 乙腈 为溶剂， 反应 0.25h， 生成 (3-(2-(2-aminopyrimidin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone
  参考文献：
  名称：

  Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor

  摘要：

  Efforts to identify potent small molecule inhibitors of PI3 kinase and mTOR led to the discovery of the exceptionally potent 6-aryl morpholino thienopyrimidine 6. In an effort to reduce the melting point in analogs of 6, the thienopyrimidine was modified by the addition of a methyl group to disrupt planarity. This modi. cation resulted in a general improvement in in vivo clearance. This discovery led to the identification of GNE-477 (8), a potent and efficacious dual PI3K/mTOR inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.046

文献信息

• PHOSPHOINOSITIDE 3-KINASE INHIBITOR COMPOUNDS AND METHODS OF USE
  申请人：Castanedo Georgette

  公开号：US20080269210A1

  公开（公告）日：2008-10-30

  Compounds of Formulas Ia-d where X is S or O, mor is a morpholine group, and R 3 is a monocyclic heteroaryl group, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for modulating the activity of lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia-d for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  化合物Ia-d的化学式中，X为S或O，mor为吗啡啶基团，R3为单环杂芳基团，包括立体异构体、几何异构体、互变异构体、溶剂化物、代谢产物和其药学上可接受的盐，对于调节脂质激酶（包括PI3K）的活性以及治疗由脂质激酶介导的癌症等疾病具有用处。本文揭示了使用化合物Ia-d进行哺乳动物细胞中的体外、体内和原位诊断、预防或治疗此类疾病或相关病理条件的方法。
• US9487533B2
  申请人：——

  公开号：US9487533B2

  公开（公告）日：2016-11-08
• [EN] PHOSPHOINOSITIDE 3-KINASE INHIBITOR COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS INHIBITEURS DE LA PHOSPHOINOSITIDE 3-KINASE ET PROCÉDÉS D'UTILISATION
  申请人：GENENTECH INC

  公开号：WO2008073785A2

  公开（公告）日：2008-06-19

  [EN] Compounds of Formulas Ia-d where X is S or O, mor is a morpholine group, and R³ is a monocyclic heteroaryl group, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for modulating the activity of lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia-d for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. Formula (Ic) and (Id).
  [FR] La présente invention concerne des composés de formules Ia à Id où X représente S ou O, mor représente un groupe morpholine, et R³ représente un groupe hétéroaryle monocyclique, et y compris les stéréoisomères, les isomères géométriques, les tautomères, les solvates, les métabolites et les sels pharmaceutiquement acceptables de ceux-ci. Lesdits composés sont utiles pour moduler l'activité de kinases lipidiques comprenant la PI3K, et pour traiter des maladies telles que le cancer provoqué par les kinases lipidiques. L'invention concerne également des procédés d'utilisation des composés de formules Ia à Id pour le diagnostic in vitro, in situ, et in vivo, la prévention ou le traitement de telles maladies dans les cellules de mammifères, ou les conditions pathologiques associées. Formules (Ic) et (Id).
• Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor
  作者：Timothy P. Heffron、Megan Berry、Georgette Castanedo、Christine Chang、Irina Chuckowree、Jennafer Dotson、Adrian Folkes、Janet Gunzner、John D. Lesnick、Cristina Lewis、Simon Mathieu、Jim Nonomiya、Alan Olivero、Jodie Pang、David Peterson、Laurent Salphati、Deepak Sampath、Steve Sideris、Daniel P. Sutherlin、Vickie Tsui、Nan Chi Wan、Shumei Wang、Susan Wong、Bing-yan Zhu

  DOI：10.1016/j.bmcl.2010.03.046

  日期：2010.4

  Efforts to identify potent small molecule inhibitors of PI3 kinase and mTOR led to the discovery of the exceptionally potent 6-aryl morpholino thienopyrimidine 6. In an effort to reduce the melting point in analogs of 6, the thienopyrimidine was modified by the addition of a methyl group to disrupt planarity. This modi. cation resulted in a general improvement in in vivo clearance. This discovery led to the identification of GNE-477 (8), a potent and efficacious dual PI3K/mTOR inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.