tert-Butyl 4-[4-({[(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)carbonyl]amino}methyl) benzyl]piperazine-1-carboxylate | 1456890-54-2

• 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: tert-Butyl 4-[4-({[(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)carbonyl]amino}methyl) benzyl]piperazine-1-carboxylate
• CAS: 1456890-54-2
• 化学式: C₂₄H₂₉N₅O₄S
• 分子量: 483.591
• InChiKey: YLUYSOLGDTVLNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  34.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  107.63
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-Butyl 4-[4-({[(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)carbonyl]amino}methyl) benzyl]piperazine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 为溶剂， 反应 40.0h， 生成 tert-butyl (2-{4-[4-({[(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)carbonyl]amino}methyl)benzyl]piperazin-1-yl}ethyl)carbamate
  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
• 作为产物：
  描述：

  N-[[4-(1,3-dioxolan-2-yl)phenyl]methyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-5-carboxamide 在 titanium(IV) isopropylate 、 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 37.0h， 生成 tert-Butyl 4-[4-({[(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)carbonyl]amino}methyl) benzyl]piperazine-1-carboxylate
  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