N-acetyl-2-[(5S)-9-fluoro-2-[4-(pyrrolidine-1-carbonyl)phenyl]-5H-chromeno[2,3-b]pyridin-5-yl]-2-methylpropanamide | 1620483-42-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-acetyl-2-[(5S)-9-fluoro-2-[4-(pyrrolidine-1-carbonyl)phenyl]-5H-chromeno[2,3-b]pyridin-5-yl]-2-methylpropanamide
• CAS: 1620483-42-2
• 化学式: C₂₉H₂₈FN₃O₄
• 分子量: 501.557
• InChiKey: NAYFBOYXQBLIBL-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  88.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-2-(2-chloro-9-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanoic acid 在 potassium phosphate 、 四(三苯基膦)钯 、 sodium hexamethyldisilazane 、 氯化铵 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-acetyl-2-[(5S)-9-fluoro-2-[4-(pyrrolidine-1-carbonyl)phenyl]-5H-chromeno[2,3-b]pyridin-5-yl]-2-methylpropanamide
  参考文献：
  名称：

  Discovery of acylurea isosteres of 2-acylaminothiadiazole in the azaxanthene series of glucocorticoid receptor agonists

  摘要：

  Acylureas and acyclic imides are found to be excellent isosteres for 2-acylamino-1,3,4-thiadiazole in the azaxanthene-based series of glucocorticoid receptor (GR) agonists. The results reported herein show that primary acylureas maintain high affinity and selectivity for GR while providing improved CYP450 inhibition and pharmacokinetic profile over 2-acylamino-1,3,4-thiadiazoles. General methods for synthesis of a variety of acylureas and acyclic imides from a carboxylic acid were utilized and are described. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.06.010

文献信息

• Discovery of acylurea isosteres of 2-acylaminothiadiazole in the azaxanthene series of glucocorticoid receptor agonists
  作者：Hua Gong、Michael Yang、Zili Xiao、Arthur M. Doweyko、Mark Cunningham、Jinhong Wang、Sium Habte、Deborah Holloway、Christine Burke、David Shuster、Ling Gao、Julie Carman、John E. Somerville、Steven G. Nadler、Luisa Salter-Cid、Joel C. Barrish、David S. Weinstein

  DOI：10.1016/j.bmcl.2014.06.010

  日期：2014.8

  Acylureas and acyclic imides are found to be excellent isosteres for 2-acylamino-1,3,4-thiadiazole in the azaxanthene-based series of glucocorticoid receptor (GR) agonists. The results reported herein show that primary acylureas maintain high affinity and selectivity for GR while providing improved CYP450 inhibition and pharmacokinetic profile over 2-acylamino-1,3,4-thiadiazoles. General methods for synthesis of a variety of acylureas and acyclic imides from a carboxylic acid were utilized and are described. (C) 2014 Elsevier Ltd. All rights reserved.