(S)-N-(2-(1-methoxypropan-2-ylamino)pyrimidin-4-yl)-N-(piperidin-4-ylmethyl)-2,3-dihydrobenzofuran-5-carboxamide | 1224600-35-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: (S)-N-(2-(1-methoxypropan-2-ylamino)pyrimidin-4-yl)-N-(piperidin-4-ylmethyl)-2,3-dihydrobenzofuran-5-carboxamide
• 英文别名: N-[2-[[(2S)-1-methoxypropan-2-yl]amino]pyrimidin-4-yl]-N-(piperidin-4-ylmethyl)-2,3-dihydro-1-benzofuran-5-carboxamide
• CAS: 1224600-35-4
• 化学式: C₂₃H₃₁N₅O₃
• 分子量: 425.531
• InChiKey: NBGUZGNZRGJWIS-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  88.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-叔丁氧羰基-4-氨甲基哌啶 在 palladium diacetate 、 sodium hydride 、 potassium carbonate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-N-(2-(1-methoxypropan-2-ylamino)pyrimidin-4-yl)-N-(piperidin-4-ylmethyl)-2,3-dihydrobenzofuran-5-carboxamide
  参考文献：
  名称：

  Amide-based inhibitors of p38α MAP kinase. Part 2: Design, synthesis and SAR of potent N-pyrimidyl amides

  摘要：

  Optimization of a tri-substituted N-pyridyl amide led to the discovery of a new class of potent N-pyrimidyl amide based p38 alpha MAP kinase inhibitors. Initial SAR studies led to the identification of 5-dihydrofuran as an optimal hydrophobic group. Additional side chain modi. cations resulted in the introduction of hydrogen bond interactions. Through extensive SAR studies, analogs bearing free amino groups and alternatives to the parent (S)-alpha-methyl benzyl moiety were identified. These compounds exhibited improved cellular activities and maintained balance between p38a and CYP3A4 inhibition. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.090

文献信息

• Amide-based inhibitors of p38α MAP kinase. Part 2: Design, synthesis and SAR of potent N-pyrimidyl amides
  作者：Richland Tester、Xuefei Tan、Gregory R. Luedtke、Imad Nashashibi、Kurt Schinzel、Weiling Liang、Joon Jung、Sundeep Dugar、Albert Liclican、Jocelyn Tabora、Daniel E. Levy、Steven Do

  DOI：10.1016/j.bmcl.2010.02.090

  日期：2010.4

  Optimization of a tri-substituted N-pyridyl amide led to the discovery of a new class of potent N-pyrimidyl amide based p38 alpha MAP kinase inhibitors. Initial SAR studies led to the identification of 5-dihydrofuran as an optimal hydrophobic group. Additional side chain modi. cations resulted in the introduction of hydrogen bond interactions. Through extensive SAR studies, analogs bearing free amino groups and alternatives to the parent (S)-alpha-methyl benzyl moiety were identified. These compounds exhibited improved cellular activities and maintained balance between p38a and CYP3A4 inhibition. (C) 2010 Elsevier Ltd. All rights reserved.