(±)-5-(1-(tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (±)-5-(1-(tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridine
• 英文别名: 5-(1-(Tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridine；tert-butyl-[2-(6-fluoropyridin-3-yl)propoxy]-dimethylsilane
• 化学式: C₁₄H₂₄FNOSi
• 分子量: 269.435
• InChiKey: KDQKXIUYNLVQGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.35
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (±)-5-(1-(tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridine 在 正丁基锂 、 硼酸三异丙酯 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.0h， 生成 (±)-5-(1-(tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridin-3-ylboronic acid
  参考文献：
  名称：

  Phosphoinositide-3-kinase inhibitors: Evaluation of substituted alcohols as replacements for the piperazine sulfonamide portion of AMG 511

  摘要：

  Replacement of the piperazine sulfonamide portion of the PI3K alpha inhibitor AMG 511 (1) with a range of aliphatic alcohols led to the identification of a truncated gem-dimethylbenzylic alcohol analog, 2-(5-(4-amino- 6-methyl-1,3,5-triazin-2-yl)-6-((5-fluoro-6-methoxypyridin-3-yl) amino) pyridin-3-yl) propan-2-ol (7). This compound possessed good in vitro efficacy and pharmacokinetic parameters and demonstrated an EC50 of 239 ng/mL in a mouse liver pharmacodynamic model measuring the inhibition of hepatocyte growth factor (HGF)-induced Akt Ser473 phosphorylation in CD1 nude mice 6 h post-oral dosing. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.085
• 作为产物：
  描述：

  2-氟-5-溴吡啶 在 硼烷四氢呋喃络合物 、 dichloro bis((p-dimethylaminophenyl)-ϖ-di-tert-butylphosphine)palladium(II) 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 7.75h， 生成 (±)-5-(1-(tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridine
  参考文献：
  名称：

  Phosphoinositide-3-kinase inhibitors: Evaluation of substituted alcohols as replacements for the piperazine sulfonamide portion of AMG 511

  摘要：

  Replacement of the piperazine sulfonamide portion of the PI3K alpha inhibitor AMG 511 (1) with a range of aliphatic alcohols led to the identification of a truncated gem-dimethylbenzylic alcohol analog, 2-(5-(4-amino- 6-methyl-1,3,5-triazin-2-yl)-6-((5-fluoro-6-methoxypyridin-3-yl) amino) pyridin-3-yl) propan-2-ol (7). This compound possessed good in vitro efficacy and pharmacokinetic parameters and demonstrated an EC50 of 239 ng/mL in a mouse liver pharmacodynamic model measuring the inhibition of hepatocyte growth factor (HGF)-induced Akt Ser473 phosphorylation in CD1 nude mice 6 h post-oral dosing. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.085

文献信息

• INHIBITORS OF PI3 KINASE AND/OR MTOR
  申请人：Andrews Kristin

  公开号：US20100273764A1

  公开（公告）日：2010-10-28

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

  本发明涉及公式I的化合物或其药学上可接受的盐；使用该化合物治疗疾病或病症的方法，如癌症；以及含有该化合物的制药组合物，其中变量在此定义。
• Inhibitors of PI3 kinase and/or mTOR
  申请人：D'Angelo Noel

  公开号：US08362241B2

  公开（公告）日：2013-01-29

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

  本发明涉及式I化合物或其药学上可接受的盐；使用该化合物治疗疾病或病症的方法，例如癌症；以及含有该化合物的药物组合物，其中变量如本文所定义。
• Inhibitors of PI3 Kinase and/or mTOR
  申请人：Amgen Inc.

  公开号：US20130079303A1

  公开（公告）日：2013-03-28

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

  本发明涉及公式I的化合物，或其药学可接受的盐；使用这些化合物治疗疾病或病况的方法，如癌症；以及含有这些化合物的药物组合物，其中变量的定义如本文所述。
• Phosphoinositide-3-kinase inhibitors: Evaluation of substituted alcohols as replacements for the piperazine sulfonamide portion of AMG 511
  作者：Brian A. Lanman、Anthony B. Reed、Victor J. Cee、Fang-Tsao Hong、Liping H. Pettus、Ryan P. Wurz、Kristin L. Andrews、Jian Jiang、John D. McCarter、Erin L. Mullady、Tisha San Miguel、Raju Subramanian、Ling Wang、Douglas A. Whittington、Tian Wu、Leeanne Zalameda、Nancy Zhang、Andrew S. Tasker、Paul E. Hughes、Mark H. Norman

  DOI：10.1016/j.bmcl.2014.10.085

  日期：2014.12

  Replacement of the piperazine sulfonamide portion of the PI3K alpha inhibitor AMG 511 (1) with a range of aliphatic alcohols led to the identification of a truncated gem-dimethylbenzylic alcohol analog, 2-(5-(4-amino- 6-methyl-1,3,5-triazin-2-yl)-6-((5-fluoro-6-methoxypyridin-3-yl) amino) pyridin-3-yl) propan-2-ol (7). This compound possessed good in vitro efficacy and pharmacokinetic parameters and demonstrated an EC50 of 239 ng/mL in a mouse liver pharmacodynamic model measuring the inhibition of hepatocyte growth factor (HGF)-induced Akt Ser473 phosphorylation in CD1 nude mice 6 h post-oral dosing. (C) 2014 Elsevier Ltd. All rights reserved.