5-(6-((4-(methylsulfonyl)piperidin-1-yl)methyl)-4-morpholinothieno[2,3-d]pyrimidin-2-yl)pyrimidin-2-amine | 1032755-77-3

• 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: 5-(6-((4-(methylsulfonyl)piperidin-1-yl)methyl)-4-morpholinothieno[2,3-d]pyrimidin-2-yl)pyrimidin-2-amine
• 英文别名: 5-[6-[(4-methylsulfonylpiperidin-1-yl)methyl]-4-morpholin-4-ylthieno[2,3-d]pyrimidin-2-yl]pyrimidin-2-amine
• CAS: 1032755-77-3
• 化学式: C₂₁H₂₇N₇O₃S₂
• 分子量: 489.622
• InChiKey: KLXMMRLIIXNDSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  33
• 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：
  164
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-氯-4-吗啡啉基噻吩并[2,3-D]嘧啶 在 正丁基锂 、 sodium carbonate 、 原甲酸三乙酯 作用下， 以 四氢呋喃 、 水 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 9.17h， 生成 5-(6-((4-(methylsulfonyl)piperidin-1-yl)methyl)-4-morpholinothieno[2,3-d]pyrimidin-2-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Rational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform

  摘要：

  Of the four class I phosphoinositide 3-kinase (PI3K) isoforms, PI3k alpha has justly received the most attention for its potential in cancer therapy. Herein we report our successful approaches to achieve PI3K alpha vs PI3K beta selectivity for two chemical series. In the thienopyrimidine series of inhibitors, we propose that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 of PI3K alpha that is not attained with the corresponding Lys777 of PI3K beta. In the benzoxepin series of inhibitors, the selectivity observed can be rationalized by the difference in electrostatic potential between the two isoforms in a given region rather than any specific interaction.

  DOI：

  10.1021/jm2007084

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：Piramed Limited

  公开号：US07888352B2

  公开（公告）日：2011-02-15

  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.

  公式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，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是有用的。公开了使用公式Ia-d的化合物进行哺乳动物细胞的体外、体内和原位诊断、预防或治疗此类疾病或相关病理情况的方法。
• US7888352B2
  申请人：——

  公开号：US7888352B2

  公开（公告）日：2011-02-15
• US8383620B2
  申请人：——

  公开号：US8383620B2

  公开（公告）日：2013-02-26
• US8993563B2
  申请人：——

  公开号：US8993563B2

  公开（公告）日：2015-03-31