ethyl (2E)-2-cyano-3-(1-methyl-1H-pyrazol-4-yl)but-2-enoate | 1456890-46-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (2E)-2-cyano-3-(1-methyl-1H-pyrazol-4-yl)but-2-enoate
• 英文别名: ethyl (E)-2-cyano-3-(1-methylpyrazol-4-yl)but-2-enoate
• CAS: 1456890-46-2
• 化学式: C₁₁H₁₃N₃O₂
• 分子量: 219.243
• InChiKey: KDVXDYLXESRPSJ-CSKARUKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  氰乙酸乙酯 、 1-(1-甲基吡唑)乙酮 在 ammonium acetate 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 18.0h， 生成 ethyl (2E)-2-cyano-3-(1-methyl-1H-pyrazol-4-yl)but-2-enoate
  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