4-methyl-N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide | 913067-83-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-methyl-N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide
• 英文别名: 4-methyl-N-[2-piperidin-1-yl-5-(trifluoromethyl)phenyl]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide
• CAS: 913067-83-1
• 化学式: C₂₆H₃₂BF₃N₂O₃
• 分子量: 488.358
• InChiKey: KTXDHVKRDMYTIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.56
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-溴-2-(N-甲基氨基)喹唑啉 、 4-methyl-N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 3.0h， 以27%的产率得到4-Methyl-3-(2-methylamino-quinazolin-6-yl)-N-(2-piperidin-1-yl-5-trifluoromethyl-phenyl)-benzamide
  参考文献：
  名称：

  Discovery of Aminoquinazolines as Potent, Orally Bioavailable Inhibitors of Lck:  Synthesis, SAR, and in Vivo Anti-Inflammatory Activity

  摘要：

  The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. Screening of our kinase-preferred collection identified aminoquinazoline 1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminoquinazolines possessing in vitro mechanism-based potency. Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory activity (ED50 of 22 and 11 mg/kg, respectively) in the anti-CD3-induced production of interleukin-2 (IL-2) in mice.

  DOI：

  10.1021/jm0605482
• 作为产物：
  描述：

  3-碘-4-甲基苯甲酸 在 氯化亚砜 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 4-methyl-N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide
  参考文献：
  名称：

  Discovery of Aminoquinazolines as Potent, Orally Bioavailable Inhibitors of Lck:  Synthesis, SAR, and in Vivo Anti-Inflammatory Activity

  摘要：

  The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. Screening of our kinase-preferred collection identified aminoquinazoline 1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminoquinazolines possessing in vitro mechanism-based potency. Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory activity (ED50 of 22 and 11 mg/kg, respectively) in the anti-CD3-induced production of interleukin-2 (IL-2) in mice.

  DOI：

  10.1021/jm0605482

文献信息

• Discovery of Aminoquinazolines as Potent, Orally Bioavailable Inhibitors of Lck:  Synthesis, SAR, and in Vivo Anti-Inflammatory Activity
  作者：Erin F. DiMauro、John Newcomb、Joseph J. Nunes、Jean E. Bemis、Christina Boucher、John L. Buchanan、William H. Buckner、Victor J. Cee、Lilly Chai、Holly L. Deak、Linda F. Epstein、Ted Faust、Paul Gallant、Stephanie D. Geuns-Meyer、Anu Gore、Yan Gu、Brad Henkle、Brian L. Hodous、Faye Hsieh、Xin Huang、Joseph L. Kim、Josie H. Lee、Matthew W. Martin、Craig E. Masse、David C. McGowan、Daniela Metz、Deanna Mohn、Kurt A. Morgenstern、Antonio Oliveira-dos-Santos、Vinod F. Patel、David Powers、Paul E. Rose、Stephen Schneider、Susan A. Tomlinson、Yan-Yan Tudor、Susan M. Turci、Andrew A. Welcher、Ryan D. White、Huilin Zhao、Li Zhu、Xiaotian Zhu

  DOI：10.1021/jm0605482

  日期：2006.9.1

  The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. Screening of our kinase-preferred collection identified aminoquinazoline 1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminoquinazolines possessing in vitro mechanism-based potency. Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory activity (ED50 of 22 and 11 mg/kg, respectively) in the anti-CD3-induced production of interleukin-2 (IL-2) in mice.