(5S)-5-(adamantan-1-yl)-2-amino-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (5S)-5-(adamantan-1-yl)-2-amino-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
• 英文别名: (5S)-2-amino-3-methyl-5-phenyl-5-[(3S,5S,7S)-tricyclo[3.3.1.1~3,7~]dec-1-yl]-3,5-dihydro-4H-imidazol-4-one；(5S)-5-(1-adamantyl)-2-amino-3-methyl-5-phenylimidazol-4-one
• 化学式: C₂₀H₂₅N₃O
• 分子量: 323.438
• InChiKey: BEDDENNXVBITIQ-ZYUPVANMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  58.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-乙炔基金刚烷 在 bis-triphenylphosphine-palladium(II) chloride 、 ammonium hydroxide 、 potassium permanganate 、 copper(l) iodide 、 二氧化碳 、 碳酸氢钠 、 magnesium sulfate 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 丙酮 、 乙腈 为溶剂， 反应 24.08h， 生成 (5R)-5-(adamantan-1-yl)-2-amino-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one 、 (5S)-5-(adamantan-1-yl)-2-amino-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
  参考文献：
  名称：

  Allosteric Modulation of Protein Arginine Methyltransferase 5 (PRMT5)

  摘要：

  Protein arginine methyltransferase 5 (PRMT5) belongs to a family of enzymes that regulate the posttranslational modification of histones and other proteins via methylation of arginine. Methylation of histones is linked to an increase in transcription and regulates a manifold of functions such as signal transduction and transcriptional regulation. PRMT5 has been shown to be upregulated in the tumor environment of several cancer types, and the inhibition of PRMT5 activity was identified as a potential way to reduce tumor growth. Previously, four different modes of PRMT5 inhibition were known-competing (covalently or non-covalently) with the essential cofactor Sadenosyl methionine (SAM), blocking the substrate binding pocket, or blocking both simultaneously. Herein we describe an unprecedented conformation of PRMT5 in which the formation of an allosteric binding pocket abrogates the enzyme's canonical binding site and present the discovery of potent small molecule allosteric PRMT5 inhibitors.

  DOI：

  10.1021/acsmedchemlett.9b00525