N-{4-[(4-hydroxypiperidin-1-yl)methyl]benzyl}-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-5-carboxamide | 1456890-41-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-{4-[(4-hydroxypiperidin-1-yl)methyl]benzyl}-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-5-carboxamide
• 英文别名: N-[[4-[(4-hydroxypiperidin-1-yl)methyl]phenyl]methyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-5-carboxamide
• CAS: 1456890-41-7
• 化学式: C₂₀H₂₂N₄O₃S
• 分子量: 398.486
• InChiKey: OKPGIPAOSZELSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(1,3-dioxacyclopent-2-yl)benzylamine 在 titanium(IV) isopropylate 、 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 49.0h， 生成 N-{4-[(4-hydroxypiperidin-1-yl)methyl]benzyl}-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-5-carboxamide
  参考文献：
  名称：

  Selective Inhibitors of Bacterial t-RNA-(N¹G37) Methyltransferase (TrmD) That Demonstrate Novel Ordering of the Lid Domain

  摘要：

  The tRNA-(N(1)G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.

  DOI：

  10.1021/jm400718n

文献信息

• Selective Inhibitors of Bacterial t-RNA-(N¹G37) Methyltransferase (TrmD) That Demonstrate Novel Ordering of the Lid Domain
  作者：Pamela J. Hill、Ayome Abibi、Robert Albert、Beth Andrews、Moriah M. Gagnon、Ning Gao、Tyler Grebe、Laurel I. Hajec、Jian Huang、Stephania Livchak、Sushmita D. Lahiri、David C. McKinney、Jason Thresher、Hongming Wang、Nelson Olivier、Ed T. Buurman

  DOI：10.1021/jm400718n

  日期：2013.9.26

  The tRNA-(N(1)G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.