6-(4-fluorophenoxy)-4-methylpyridin-3-amine | 753921-02-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(4-fluorophenoxy)-4-methylpyridin-3-amine
• 英文别名: 6-(4-Fluorophenoxy)-4-methylpyridin-3-amine
• CAS: 753921-02-7
• 化学式: C₁₂H₁₁FN₂O
• 分子量: 218.231
• InChiKey: VKCAUUBNQFRHTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  48.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4-fluorophenoxy)-4-methylpyridin-3-amine 在 盐酸 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 N,N-二异丙基乙胺 、 sodium nitrite 作用下， 以 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 18.5h， 生成 4-(1-(6-(4-fluorophenoxy)-4-methylpyridin-3-yl)-1H-1,2,3-triazol-4-yl)benzoic acid
  参考文献：
  名称：

  Hit-to-lead optimization of a latency-associated nuclear antigen inhibitor against Kaposi’s sarcoma-associated herpesvirus infections

  摘要：

  The Latency-associated nuclear antigen (LANA) plays a central role for the latent persistence of the Kaposi's Sarcoma Herpesvirus (KSHV) in the human host and helps to establish lifelong infections. Herein, we report our efforts towards hit-to-lead generation starting from a previously discovered LANADNA inhibitor. By tethering the viral genome to the host nucleosomes, LANA ensures the segregation and persistence of the viral DNA during mitosis. LANA is also required for the replication of the latent viral episome during the S phase of the cell cycle. We aim to inhibit the interaction between LANA and the viral genome to prevent the latent persistence of KSHV in the host organism. Medicinal chemistry-driven optimization studies and structure-activity-relationship investigation led to the discovery of an improved LANA inhibitor. The functional activity of our compounds was evaluated using a fluorescence polarization (FP)-based interaction inhibition assay and electrophoretic mobility shift assay (EMSA). Even though a crystal structure of the ligand protein complex was not available, we successfully conducted hit optimization toward a low micromolar protein-nucleic acid-interaction inhibitor. Additionally, we applied STD-NMR studies to corroborate target binding and to gain insights into the binding orientation of our most potent inhibitor, providing opportunities for further rational design of more efficient LANAtargeting anti KSHV agents in future studies. (C) 2020 The Author(s). Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2020.112525
• 作为产物：
  描述：

  Pyridine,2-(4-fluorophenoxy)-4-methyl-5-nitro- 在 palladium dihydroxide 甲酸铵 作用下， 以 乙醇 为溶剂， 生成 6-(4-fluorophenoxy)-4-methylpyridin-3-amine
  参考文献：
  名称：

  P38 inhibitors and methods of use thereof

  摘要：

  这项发明涉及p38的抑制剂，以及生产这些抑制剂的方法。该发明还提供了包括该发明中的抑制剂的药物组合物，以及利用这些抑制剂和药物组合物在治疗和预防由p38介导的各种疾病中的方法。

  公开号：

  US20040176325A1