5-acetamido-4-amino-2,6-anhydro-3,4,5-trideoxy-6-((phenylamino)methyl)-L-gluco-hex-2-enonic acid | 1428441-18-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-acetamido-4-amino-2,6-anhydro-3,4,5-trideoxy-6-((phenylamino)methyl)-L-gluco-hex-2-enonic acid
• 英文别名: (2S,3R,4S)-3-acetamido-4-amino-2-(anilinomethyl)-3,4-dihydro-2H-pyran-6-carboxylic acid
• CAS: 1428441-18-2
• 化学式: C₁₅H₁₉N₃O₄
• 分子量: 305.334
• InChiKey: PYBCZACBPIQGQG-FPMFFAJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  114
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  methyl 5-acetamido-2,6-anhydro-4-azido-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enonic acid 在 sodium periodate 、 氢气 、 sodium cyanoborohydride 、 溶剂黄146 、 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 1.5h， 生成 5-acetamido-4-amino-2,6-anhydro-3,4,5-trideoxy-6-((phenylamino)methyl)-L-gluco-hex-2-enonic acid
  参考文献：
  名称：

  Identification of Selective Inhibitors for Human Neuraminidase Isoenzymes Using C4,C7-Modified 2-Deoxy-2,3-didehydro-N-acetylneuraminic Acid (DANA) Analogues

  摘要：

  In the past two decades, human neuraminidases (human sialidases, hNEUs) have been found to be involved in numerous pathways in biology. The development of selective and potent inhibitors of these enzymes will provide critical tools for glycobiology, help to avoid undesired side effects of antivirals, and may reveal new small-molecule therapeutic targets for human cancers. However, because of the high active site homology of the hNEU isoenzymes, little progress in the design and synthesis of selective inhibitors has been realized. Guided by our previous studies of human NEU3 inhibitors, we designed a series of C4,C7-modified analogues of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA) and tested them against the full panel of hNEU isoenzymes (NEU1, NEU2, NEU3, NEU4). We identified inhibitors with up to 38-fold selectivity for NEU3 and 12-fold selectivity for NEU2 over all other isoenzymes. We also identified compounds that targeted NEU2 and NEU3 with similar potency.

  DOI：

  10.1021/jm301892f

文献信息

• Identification of Selective Inhibitors for Human Neuraminidase Isoenzymes Using C4,C7-Modified 2-Deoxy-2,3-didehydro-<i>N</i>-acetylneuraminic Acid (DANA) Analogues
  作者：Yi Zhang、Amgad Albohy、Yao Zou、Victoria Smutova、Alexey V. Pshezhetsky、Christopher W. Cairo

  DOI：10.1021/jm301892f

  日期：2013.4.11

  In the past two decades, human neuraminidases (human sialidases, hNEUs) have been found to be involved in numerous pathways in biology. The development of selective and potent inhibitors of these enzymes will provide critical tools for glycobiology, help to avoid undesired side effects of antivirals, and may reveal new small-molecule therapeutic targets for human cancers. However, because of the high active site homology of the hNEU isoenzymes, little progress in the design and synthesis of selective inhibitors has been realized. Guided by our previous studies of human NEU3 inhibitors, we designed a series of C4,C7-modified analogues of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA) and tested them against the full panel of hNEU isoenzymes (NEU1, NEU2, NEU3, NEU4). We identified inhibitors with up to 38-fold selectivity for NEU3 and 12-fold selectivity for NEU2 over all other isoenzymes. We also identified compounds that targeted NEU2 and NEU3 with similar potency.