4-((2-chloro-9-methyl-8-(4-(methylsulfonyl)piperazin-1-yl)methyl)-9H-purin-6-yl)morpholine | 1198171-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 4-((2-chloro-9-methyl-8-(4-(methylsulfonyl)piperazin-1-yl)methyl)-9H-purin-6-yl)morpholine
• 英文别名: 4-(2-Chloro-9-methyl-8-((4-(methylsulfonyl)piperazin-1-yl)methyl)-9H-purin-6-yl)morpholine；4-[2-chloro-9-methyl-8-[(4-methylsulfonylpiperazin-1-yl)methyl]purin-6-yl]morpholine
• CAS: 1198171-83-3
• 化学式: C₁₆H₂₄ClN₇O₃S
• 分子量: 429.931
• InChiKey: LYELADDLIVDNSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-乙基苯并咪唑 、 4-((2-chloro-9-methyl-8-(4-(methylsulfonyl)piperazin-1-yl)methyl)-9H-purin-6-yl)morpholine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以77%的产率得到4-[2-(2-Ethylbenzimidazol-1-yl)-9-methyl-8-[(4-methylsulfonylpiperazin-1-yl)methyl]purin-6-yl]morpholine
  参考文献：
  名称：

  Potent and Highly Selective Benzimidazole Inhibitors of PI3-Kinase Delta

  摘要：

  Inhibition of PI3K delta is considered to be an attractive mechanism for the treatment of inflammatory diseases and leukocyte malignancies. Using a structure-based design approach, we have identified a series of potent and selective benzimidazole-based inhibitors of PI3K delta. These inhibitors do not occupy the selectivity pocket between Trp760 and Met752 that is induced by other families of PI3K delta inhibitors. Instead, the selectivity of the compounds for inhibition of PI3K delta relative to other PI3K isoforms appears to be due primarily to the strong interactions these inhibitors are able to make with Trp760 in the PI3K delta binding pocket. The pharmacokinetic properties and the ability of compound 5 to inhibit the function of B-cells in vivo are described.

  DOI：

  10.1021/jm300717c
• 作为产物：
  描述：

  4-(2-氯-9-甲基嘌呤-6-基)吗啉 在 正丁基锂 、 溶剂黄146 、 原甲酸三甲酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 4-((2-chloro-9-methyl-8-(4-(methylsulfonyl)piperazin-1-yl)methyl)-9H-purin-6-yl)morpholine
  参考文献：
  名称：

  [EN] PURINE PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
  [FR] COMPOSÉS INHIBITEURS DE LA PI3K DE TYPE PURINE ET PROCÉDÉS D'UTILISATION

  摘要：

  公式I的嘌呤化合物，包括立体异构体、几何异构体、互变异构体、溶剂化合物、代谢物和其药用可接受盐，可用于抑制脂质激酶，包括p110 alpha和PI3K的其他同工酶，并用于治疗由脂质激酶介导的癌症等疾病。揭示了使用公式I的化合物在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗这类疾病或相关病理状况的方法。

  公开号：

  WO2009146406A1

文献信息

• [EN] PURINE PI3K INHIBITOR COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS INHIBITEURS DE LA PI3K DE TYPE PURINE ET PROCÉDÉS D'UTILISATION
  申请人：GENENTECH INC

  公开号：WO2009146406A1

  公开（公告）日：2009-12-03

  Purine compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式I的嘌呤化合物，包括立体异构体、几何异构体、互变异构体、溶剂化合物、代谢物和其药用可接受盐，可用于抑制脂质激酶，包括p110 alpha和PI3K的其他同工酶，并用于治疗由脂质激酶介导的癌症等疾病。揭示了使用公式I的化合物在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗这类疾病或相关病理状况的方法。
• PURINE PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
  申请人：Castanedo Georgette

  公开号：US20090318411A1

  公开（公告）日：2009-12-24

  Purine compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式I中的嘌呤化合物，包括立体异构体、几何异构体、互变异构体、溶剂化物、代谢物和其药学上可接受的盐，可用于抑制脂质激酶，包括p110 alpha和其他PI3K同工酶，并用于治疗由脂质激酶介导的癌症等疾病。公开了使用公式I中的化合物进行哺乳动物细胞的体外、原位和体内诊断、预防或治疗此类疾病或相关病理条件的方法。
• Purine PI3K inhibitor compounds and methods of use
  申请人：Genetech, Inc.

  公开号：US08158624B2

  公开（公告）日：2012-04-17

  Purine compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式I中的嘌呤化合物，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等，对于抑制脂质激酶包括p110 alpha和PI3K的其他亚型以及治疗由脂质激酶介导的癌症等疾病具有用途。本文揭示了使用公式I中的化合物进行哺乳动物细胞内、原位和体内诊断、预防或治疗此类疾病或相关病理条件的方法。
• US8158624B2
  申请人：——

  公开号：US8158624B2

  公开（公告）日：2012-04-17
• US8445487B2
  申请人：——

  公开号：US8445487B2

  公开（公告）日：2013-05-21