2,4-二氯-7,7-二甲基-5,7-二氢呋喃并[3,4-d]嘧啶 | 1260088-72-9

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 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: 2,4-二氯-7,7-二甲基-5,7-二氢呋喃并[3,4-d]嘧啶
• 英文名称: 2,4-dichloro-7,7-dimethyl-5,7-dihydrofuro[3,4-d]pyrimidine
• 英文别名: 2,4-dichloro-7,7-dimethyl-5H-furo[3,4-d]pyrimidine
• CAS: 1260088-72-9
• 化学式: C₈H₈Cl₂N₂O
• 分子量: 219.07
• InChiKey: IGGHWEUEJMUGHP-UHFFFAOYSA-N

物化性质

• 沸点：
  317.6±42.0 °C(Predicted)
• 密度：
  1.383±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2,4-二氯-7,7-二甲基-5,7-二氢呋喃并[3,4-d]嘧啶 在 四(三苯基膦)钯 、 potassium acetate 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 15.5h， 生成 (S)-1-(4-(7,7-dimethyl-4-(3-methylmorpholino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)phenyl)-3-(oxetan-3-yl)urea
  参考文献：
  名称：

  Potent, Selective, and Orally Bioavailable Inhibitors of Mammalian Target of Rapamycin (mTOR) Kinase Based on a Quaternary Substituted Dihydrofuropyrimidine

  摘要：

  A series of inhibitors of mTOR kinase based on a quaternary-substituted dihydrofuropyrimidine was designed and synthesized. The most potent compounds in this series inhibited mTOR kinase with K-i < 1.0 nM and were highly (>100x) selective for mTOR over the closely related PI3 kinases. Compounds in this series showed inhibition of the pathway and antiproliferative activity in cell-based assays. Furthermore, these compounds had excellent mouse PK, and showed a robust PK-PD relationship in a mouse model of cancer.

  DOI：

  10.1021/jm200215y
• 作为产物：
  描述：

  7,7-dimethyl-5,7-dihydrofuro[3,4-d]pyrimidine-2,4(1H,3H)-dione 在 三氯氧磷 、 碳酸氢钠 作用下， 以 1,2-二氯乙烷 、 二氯甲烷 、 水 为溶剂， 反应 20.0h， 以82%的产率得到2,4-二氯-7,7-二甲基-5,7-二氢呋喃并[3,4-d]嘧啶
  参考文献：
  名称：

  OXO-HETEROCYCLE FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE

  摘要：

  公开的是Formula I的化合物，包括立体异构体、几何异构体、互变异构体、溶剂合物、代谢物及其药学上可接受的盐，这些化合物在调节PIKK相关激酶信号传导方面很有用，例如mTOR，并用于治疗至少部分由PIKK信号传导途径失调引起的疾病（例如癌症）。

  公开号：

  US20100331305A1
• 作为试剂：
  描述：

  7,7-dimethyl-5,7-dihydrofuro[3,4-d]pyrimidine-2,4(1H,3H)-dione 、 三氯氧磷 、 1,2-二氯乙烷 在 2,4-二氯-7,7-二甲基-5,7-二氢呋喃并[3,4-d]嘧啶 、 二氯甲烷 、 碳酸氢钠 、 Sodium sulfate-III 作用下， 反应 20.0h， 以to afford 2.53 g (82%) of 2,4-dichloro-7,7-dimethyl-5,7-dihydrofuro[3,4-d]pyrimidine (p) as a colorless solid的产率得到2,4-二氯-7,7-二甲基-5,7-二氢呋喃并[3,4-d]嘧啶
  参考文献：
  名称：

  OXO-HETEROCYCLE FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE

  摘要：

  本发明涉及式I的化合物，包括其立体异构体、几何异构体、互变异构体、溶剂合物、代谢物和药学上可接受的盐，这些化合物对调节PIKK相关激酶信号传导，例如mTOR，并用于治疗通过PIKK信号通路失调（例如mTOR）至少部分介导的疾病（例如癌症）是有用的。

  公开号：

  US20100331305A1

文献信息

• 4-Aminoindazolyl-dihydrofuro[3,4- d ]pyrimidines as non-covalent inhibitors of mutant epidermal growth factor receptor tyrosine kinase
  作者：Emily J. Hanan、Matt Baumgardner、Marian C. Bryan、Yuan Chen、Charles Eigenbrot、Peter Fan、Xiao-Hui Gu、Hank La、Shiva Malek、Hans E. Purkey、Gabriele Schaefer、Stephen Schmidt、Steve Sideris、Ivana Yen、Christine Yu、Timothy P. Heffron

  DOI：10.1016/j.bmcl.2015.11.078

  日期：2016.1

  The treatment of epidermal growth factor receptor (EGFR)-driven non-small cell lung cancers with the T790M resistance mutation remains a significant unmet medical need. We report the identification of 4-aminoindazolyl-dihydrofuro[3,4-d] pyrimidines as non-covalent inhibitors of EGFR, with excellent activity against the T790M resistance double mutants and initial single activating mutants. Using an optimization strategy focused on structure-based design and improving PK properties through metabolite identification, we obtained advanced leads with high oral exposure. (C) 2015 Elsevier Ltd. All rights reserved.
• [EN] OXO-HETEROCYCLE FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSÉS PYRIMIDINE FUSIONNÉS À OXO-HÉTÉROCYCLES, COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：GENENTECH INC

  公开号：WO2010151601A1

  公开（公告）日：2010-12-29

  Disclosed are compounds of Formula (I), including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR). Formula (I).
• OXO-HETEROCYCLE FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Bergeron Philippe

  公开号：US20100331305A1

  公开（公告）日：2010-12-30

  Disclosed are compounds of Formula I, including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR).

  公开的是Formula I的化合物，包括立体异构体、几何异构体、互变异构体、溶剂合物、代谢物及其药学上可接受的盐，这些化合物在调节PIKK相关激酶信号传导方面很有用，例如mTOR，并用于治疗至少部分由PIKK信号传导途径失调引起的疾病（例如癌症）。
• Potent, Selective, and Orally Bioavailable Inhibitors of Mammalian Target of Rapamycin (mTOR) Kinase Based on a Quaternary Substituted Dihydrofuropyrimidine
  作者：Frederick Cohen、Philippe Bergeron、Elizabeth Blackwood、Krista K. Bowman、Huifen Chen、Antonio G. DiPasquale、Jennifer A. Epler、Michael F. T. Koehler、Kevin Lau、Cristina Lewis、Lichuan Liu、Cuong Q. Ly、Shiva Malek、Jim Nonomiya、Daniel F. Ortwine、Zhonghua Pei、Kirk D. Robarge、Steve Sideris、Lan Trinh、Tom Truong、Jiansheng Wu、Xianrui Zhao、Joseph P. Lyssikatos

  DOI：10.1021/jm200215y

  日期：2011.5.12

  A series of inhibitors of mTOR kinase based on a quaternary-substituted dihydrofuropyrimidine was designed and synthesized. The most potent compounds in this series inhibited mTOR kinase with K-i < 1.0 nM and were highly (>100x) selective for mTOR over the closely related PI3 kinases. Compounds in this series showed inhibition of the pathway and antiproliferative activity in cell-based assays. Furthermore, these compounds had excellent mouse PK, and showed a robust PK-PD relationship in a mouse model of cancer.