(1R,2R)-4-(5-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-4-hydroxy-N-(2-hydroxycyclopentyl)-2-oxobut-3-enamide | 1445954-00-6

• 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: (1R,2R)-4-(5-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-4-hydroxy-N-(2-hydroxycyclopentyl)-2-oxobut-3-enamide
• 英文别名: (1R,2R)-4-(5-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-2-hydroxy-N-(2-hydroxycyclopentyl)-4-oxobut-2-enamide；4-[5-[(2,4-difluorophenyl)methyl]-1-[(2-fluorophenyl)methyl]-2-oxopyridin-3-yl]-4-hydroxy-N-[(1R,2R)-2-hydroxycyclopentyl]-2-oxobut-3-enamide
• CAS: 1445954-00-6
• 化学式: C₂₈H₂₅F₃N₂O₅
• 分子量: 526.512
• InChiKey: XHMXPFAWUFEBCJ-DNQXCXABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-(2,4-difluorobenzyl)-3-iodopyridin-2(1H)-one 在 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 (1R,2R)-4-(5-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-4-hydroxy-N-(2-hydroxycyclopentyl)-2-oxobut-3-enamide
  参考文献：
  名称：

  Notable difference in anti-HIV activity of integrase inhibitors as a consequence of geometric and enantiomeric configurations

  摘要：

  While some examples are known of integrase inhibitors that exhibit potent anti-HIV activity, there are very few cases reported of integrase inhibitors that show significant differences in anti-HIV activity that result from distinctions in cis- and trans-configurations as well as enantiomeric stereostructure. We describe here the design and synthesis of two enantiomeric trans-hydroxycyclopentyl carboxamides which exhibit notable difference in anti-HIV activity. This difference is explained through their binding interactions within the active site of the HIV-1 integrase intasome. The more active enantiomer 3 (EC50 25 nM) was relatively stable in human liver microsomes. Kinetic data revealed that its impact on key cytochrome P450 isozymes, as either an inhibitor or an activator, was minor, suggesting a favorable CYP profile. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.050