5-(4-methoxybenzyl)-5-(8-methylnonyl)pyrimidine-2,4,6(1H,3H,5H)-trione | 1138154-90-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(4-methoxybenzyl)-5-(8-methylnonyl)pyrimidine-2,4,6(1H,3H,5H)-trione
• 英文别名: 5-[(4-Methoxyphenyl)methyl]-5-(8-methylnonyl)-1,3-diazinane-2,4,6-trione；5-[(4-methoxyphenyl)methyl]-5-(8-methylnonyl)-1,3-diazinane-2,4,6-trione
• CAS: 1138154-90-1
• 化学式: C₂₂H₃₂N₂O₄
• 分子量: 388.507
• InChiKey: JSEADFAWCUECMR-UHFFFAOYSA-N

物化性质

• 密度：
  1.082±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-benzyloxy-5-methylnonane 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 52.5h， 生成 5-(4-methoxybenzyl)-5-(8-methylnonyl)pyrimidine-2,4,6(1H,3H,5H)-trione
  参考文献：
  名称：

  Validating the 1,2-Difluoro Motif As a Hybrid Bioisostere of CF₃ and Et Using Matrix Metalloproteinases As Structural Probes

  摘要：

  Matrix metalloproteinases (MMPs) are involved in a spectrum of physiological processes, rendering them attractive targets for small-molecule drug discovery. Strategies to achieve selective inhibition continue to be intensively pursued, facilitated by advances in structural biology. Herein, we harness MMPs 2, 8, 9, and 13 to validate the vicinal difluoro motif as a hybrid bioisostere of CF3 and Et (BITE) in a series of modified barbiturate inhibitors. Crystallographic analyses of representative structures reveal conformations of the vicinal difluoro motif that manifest stabilizing hyperconjugative interactions consistent with the stereoelectronic gauche effect. Detailed docking studies of a potent difluorinated probe with MMP-9 are also disclosed and indicate that the structural basis of inhibition is a consequence of the anisotropic nature of the motif. Significant selectivity of MMP 13 versus MMP-2 can be achieved by subtle chain contraction in a BITE-modified inhibitor.

  DOI：

  10.1021/acs.jmedchem.0c00648

文献信息

• Validating the 1,2-Difluoro Motif As a Hybrid Bioisostere of CF₃ and Et Using Matrix Metalloproteinases As Structural Probes
  作者：Nathalie Erdeljac、Christian Thiehoff、Ravindra P. Jumde、Constantin G. Daniliuc、Sandra Höppner、Andreas Faust、Anna K. H. Hirsch、Ryan Gilmour

  DOI：10.1021/acs.jmedchem.0c00648

  日期：2020.6.11

  Matrix metalloproteinases (MMPs) are involved in a spectrum of physiological processes, rendering them attractive targets for small-molecule drug discovery. Strategies to achieve selective inhibition continue to be intensively pursued, facilitated by advances in structural biology. Herein, we harness MMPs 2, 8, 9, and 13 to validate the vicinal difluoro motif as a hybrid bioisostere of CF3 and Et (BITE) in a series of modified barbiturate inhibitors. Crystallographic analyses of representative structures reveal conformations of the vicinal difluoro motif that manifest stabilizing hyperconjugative interactions consistent with the stereoelectronic gauche effect. Detailed docking studies of a potent difluorinated probe with MMP-9 are also disclosed and indicate that the structural basis of inhibition is a consequence of the anisotropic nature of the motif. Significant selectivity of MMP 13 versus MMP-2 can be achieved by subtle chain contraction in a BITE-modified inhibitor.