4-morpholin-4-yl-2-[3-(1,1,2,2-tetramethylpropylsilanyloxy)phenyl]thieno[3,2-d]pyrimidine | 885616-90-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 4-morpholin-4-yl-2-[3-(1,1,2,2-tetramethylpropylsilanyloxy)phenyl]thieno[3,2-d]pyrimidine
• 英文别名: 4-(2-(3-(tert-butyldimethylsilyloxy)phenyl)thieno[3,2-d]pyrimidin-4-yl)morpholine；tert-butyl-dimethyl-[3-(4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl)phenoxy]silane
• CAS: 885616-90-0
• 化学式: C₂₂H₂₉N₃O₂SSi
• 分子量: 427.643
• InChiKey: WZXIMMDWSQGNJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.58
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  75.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-morpholin-4-yl-2-[3-(1,1,2,2-tetramethylpropylsilanyloxy)phenyl]thieno[3,2-d]pyrimidine 、 N-Boc-溴乙胺 在 正丁基锂 作用下， 以 四氢呋喃 、 hexanes 为溶剂， 生成 tert-butyl 2-(2-(3-(tert-butyldimethylsilyloxy)phenyl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)ethylcarbamate
  参考文献：
  名称：

  [EN] TRIAZINE, PYRIMIDINE AND PYRIDINE ANALOGS AND THEIR USE AS THERAPEUTIC AGENTS AND DIAGNOSTIC PROBES
  [FR] ANALOGUES DE TRIAZINE, PYRIMIDINE ET PYRIDINE ET LEUR UTILISATION EN TANT QU'AGENTS THÉRAPEUTIQUES ET SONDES DE DIAGNOSTIC

  摘要：

  公开号：

  WO2010052569A8
• 作为产物：
  描述：

  3-(叔丁二甲硅氧基)苯硼酸 、 2-氯-4-(4-吗啉基)噻吩并[3,2-D]嘧啶 在 bis-triphenylphosphine-palladium(II) chloride 、 碳酸氢钠 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 16.0h， 以51%的产率得到4-morpholin-4-yl-2-[3-(1,1,2,2-tetramethylpropylsilanyloxy)phenyl]thieno[3,2-d]pyrimidine
  参考文献：
  名称：

  The Identification of 2-(1H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a Potent, Selective, Orally Bioavailable Inhibitor of Class I PI3 Kinase for the Treatment of Cancer

  摘要：

  Phosphatidylinositol-3-kinase (PI3K) is an important target in cancer due to the deregulation of the PI3K/ Akt signaling pathway in a wide variety of tumors. A series of thieno[3,2-d]pyrimidine derivatives were prepared and evaluated as inhibitors of PI3 kinase p110alpha. The synthesis, biological activity, and further profiling of these compounds are described. This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer.

  DOI：

  10.1021/jm800295d

文献信息

• Pharmaceutical compounds
  申请人：Shuttleworth Stephen J.

  公开号：US20080207609A1

  公开（公告）日：2008-08-28

  Fused pyrimidines of formula (I): wherein R 1 -R 3 , A and n have any of the values described in the specification; and pharmaceutically acceptable salts thereof; have activity as inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behavior associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.

  式(I)的融合嘧啶类化合物： 其中R1-R3、A和n的取值如规范所述；以及其药学上可接受的盐；具有抑制PI3K的活性，因此可用于治疗由与PI3激酶相关的异常细胞生长、功能或行为引起的疾病和障碍，如癌症、免疫障碍、心血管疾病、病毒感染、炎症、代谢/内分泌障碍和神经障碍。还描述了合成这些化合物的过程。
• TRIAZINE, PYRIMIDINE AND PYRIDINE ANALOGS AND THEIR USE AS THERAPEUTIC AGENTS AND DIAGNOSTIC PROBES
  申请人：Cmiljanovic Vladimir

  公开号：US20110275762A1

  公开（公告）日：2011-11-10

  The invention relates to novel therapeutic agents and diagnostic probes. The invention also relates to phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor triazine-, pyrimidine- and pyridine-based compoundŝ Formula (I), their stereoisomers, geometric isomers, tautomers, solvates, metabolites, N-oxide derivatives, pharmaceutically acceptable salts, and prodrugs thereof compositions of the new compounds; either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, for treating disorders 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. (Formula I)

  本发明涉及新型治疗剂和诊断探针。本发明还涉及磷脂酰肌醇3-激酶（PI3K）和哺乳动物雷帕霉素靶蛋白酶（mTOR）抑制剂三嗪基、嘧啶基和吡啶基化合物̂公式（I），它们的立体异构体、几何异构体、互变异构体、溶剂化物、代谢物、N-氧化衍生物、药学上可接受的盐以及前药的组合物；新化合物的组合物，可以单独使用或与至少一种额外的治疗剂结合，与药学上可接受的载体；以及使用新化合物的方法，可以单独使用或与至少一种额外的治疗剂结合，用于治疗由脂质激酶介导的疾病。公开了使用公式（I）化合物的方法，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗这种疾病或相关病理条件。(公式I)
• Triazine, pyrimidine and pyridine analogs and their use as therapeutic agents and diagnostic probes
  申请人：Cmiljanovic Vladimir

  公开号：US08921361B2

  公开（公告）日：2014-12-30

  The invention relates to novel therapeutic agents and diagnostic probes. The invention also relates to phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor triazine-, pyrimidine- and pyridine-based compounds^ Formula (I), their stereoisomers, geometric isomers, tautomers, solvates, metabolites, N-oxide derivatives, pharmaceutically acceptable salts, and prodrugs thereof compositions of the new compounds; either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, for treating disorders 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. (Formula I)

  本发明涉及新型治疗剂和诊断探针。本发明还涉及磷脂酰肌醇3-激酶（PI3K）和哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂三嗪、嘧啶和吡啶基化合物的式（I），它们的立体异构体、几何异构体、互变异构体、溶剂化物、代谢物、N-氧化衍生物、药学上可接受的盐和其前药化合物的组合物。新化合物的组合物可以单独使用或与至少一种额外的治疗剂联合使用，并与药学上可接受的载体一起使用，用于治疗由脂质激酶介导的疾病。本发明还揭示了使用式（I）化合物的方法，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗这种疾病或相关的病理情况。 （式I）