GNE-477抑制剂 | 1032754-81-6

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: GNE-477抑制剂
• 英文名称: GNE-477
• 英文别名: 5-(7-Methyl-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine；5-[7-methyl-6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine
• CAS: 1032754-81-6
• 化学式: C₂₁H₂₈N₈O₃S₂
• 分子量: 504.637
• InChiKey: AKKCGLXULFRAET-UHFFFAOYSA-N

物化性质

• 密度：
  1.51±0.1 g/cm3(Predicted)
• 溶解度：
  不溶于水；不溶于乙醇；温和加热下 DMSO 中≥16.69 mg/mL

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：
  0.52
• 拓扑面积：
  167
• 氢给体数：
  1
• 氢受体数：
  12

制备方法与用途

生物活性

GNE-477 是有效的 PI3K/mTOR 抑制剂，对 PI3Kα 的 IC50 值为 4 nM，对 mTOR 的 Kiapp 值为 21 nM。

靶点

Target	Value
PI3Kα (细胞外分析)	4 nM
mTOR (细胞外分析)	21 nM (Kiapp)
mTOR (细胞外分析)	21 nM (Kiapp)

反应信息

• 作为产物：
  描述：

  2-氨基嘧啶-5-硼酸频哪酯 、 2-chloro-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-7-methyl-4-morpholin-4-yl-thieno[3,2-d]pyrimidine 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium acetate 作用下， 以 水 、 乙腈 为溶剂， 反应 0.25h， 生成 GNE-477抑制剂
  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：Bayliss Tracy

  公开号：US20080242665A1

  公开（公告）日：2008-10-02

  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.

  化学式Ia-d的化合物，其中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、代谢物和药学上可接受的盐，可用于调节脂质激酶包括PI3K的活性，并用于治疗由脂质激酶介导的癌症等疾病。本文公开了使用化合物Ia-d的方法，用于哺乳动物细胞中体外、体内诊断、预防或治疗这种疾病或相关病理条件。
• Phosphoinositide 3-kinase inhibitor compounds and methods of use
  申请人：F.Hoffmann-La Roche AG

  公开号：EP2518074A1

  公开（公告）日：2012-10-31

  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.

  式Ia-d化合物（其中X为S或O，mor为吗啉基团，R3为单环杂芳基），包括立体异构体、几何异构体、同分异构体、溶解物、代谢物及其药学上可接受的盐，可用于调节脂质激酶（包括PI3K）的活性，以及治疗由脂质激酶介导的疾病（如癌症）。公开了使用式 Ia-d 化合物体外、原位和体内诊断、预防或治疗哺乳动物细胞中的此类疾病或相关病理状况的方法。
• Compositions for the treatment of pancreatic cancer and uses thereof
  申请人：University of Florida Research Foundation, Incorporated

  公开号：US10835524B2

  公开（公告）日：2020-11-17

  The invention pertains to compositions comprising inhibitors of PI3K, AKT and/or mTOR, one or more 4-quinolinemethanols and a pharmaceutically acceptable excipient. These compositions can contain subtherapeutic amounts of each active ingredient (PI3K, AKT, mTOR, one or more 4-quinolinemethanols and various combinations thereof). The invention also provides a method of treating various forms of cancer, such as breast cancer, prostate cancer, multiple myeloma, hepatocyte carcinoma, brain cancer, lung cancer, non-small cell lung carcinoma, colorectal cancer, melanoma and/or pancreatic cancer.

  本发明涉及由 PI3K、AKT 和/或 mTOR 抑制剂、一种或多种 4-喹啉甲醇和药学上可接受的赋形剂组成的组合物。这些组合物可以包含亚治疗量的每种活性成分（PI3K、AKT、mTOR、一种或多种 4-喹啉甲醇及其各种组合）。本发明还提供了一种治疗各种形式癌症的方法，如乳腺癌、前列腺癌、多发性骨髓瘤、肝细胞癌、脑癌、肺癌、非小细胞肺癌、结直肠癌、黑色素瘤和/或胰腺癌。
• Combination therapies
  申请人：Infinity Pharmaceuticals, Inc.

  公开号：US11110096B2

  公开（公告）日：2021-09-07

  Provided herein are pharmaceutical compositions comprising a phosphatidylinositol 3-kinase inhibitor or a pharmaceutically acceptable form thereof, and a Bcl-2 inhibitor or a pharmaceutically acceptable form thereof. Also provided herein are methods for treating cancer comprising administration the compositions, and uses of the compositions, e.g., for the treatment of cancer.

  本文提供的药物组合物包含磷脂酰肌醇3-激酶抑制剂或其药学上可接受的形式，以及Bcl-2抑制剂或其药学上可接受的形式。本文还提供了治疗癌症的方法，包括给药该组合物，以及该组合物的用途，例如用于治疗癌症。
• METHOD FOR PREPARING AND DELIVERING BISANTRENE FORMULATIONS
  申请人：Race Oncology Ltd.

  公开号：EP3860575A1

  公开（公告）日：2021-08-11