4-叠氮基-3-甲基吡啶 | 95680-54-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 4-叠氮基-3-甲基吡啶
• 英文名称: 4-azido-3-methylpyridine
• CAS: 95680-54-9
• 化学式: C₆H₆N₄
• 分子量: 134.14
• InChiKey: SMEQYUMYGAHTCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  27.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-乙炔基苯甲酸 、 4-叠氮基-3-甲基吡啶 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 为溶剂， 反应 16.0h， 以77%的产率得到4-(1-(3-methylpyridin-4-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：

  3-甲基-4-氨基吡啶 在 盐酸 、 sodium nitrite 、 sodium azide 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 2.5h， 生成 4-叠氮基-3-甲基吡啶
  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

文献信息

• Ohba, Yoshihiro; Matsukura, Ikuo; Fukazawa, Yoshimasa, Heterocycles, 1985, vol. 23, # 2, p. 287 - 290
  作者：Ohba, Yoshihiro、Matsukura, Ikuo、Fukazawa, Yoshimasa、Nishiwaki, Tarozaemon

  DOI：——

  日期：——
• Sawanishi, Hiroyuki; Tajima, Kayoko; Tsuchiya, Takashi, Chemical and pharmaceutical bulletin, 1987, vol. 35, # 8, p. 3175 - 3181
  作者：Sawanishi, Hiroyuki、Tajima, Kayoko、Tsuchiya, Takashi

  DOI：——

  日期：——
• Sawanishi, Hiroyuki; Tajima, Kayoko; Osada, Makoto, Chemical and pharmaceutical bulletin, 1984, vol. 32, # 11, p. 4694 - 4697
  作者：Sawanishi, Hiroyuki、Tajima, Kayoko、Osada, Makoto、Tsuchiya, Takashi

  DOI：——

  日期：——
• SAWANISHI, HIROYUKI;TAJIMA, KAYOKO;OSADA, MAKOTO;TSUCHIYA, TAKASHI, CHEM. AND PHARM. BULL., 1984, 32, N 11, 4694-4697
  作者：SAWANISHI, HIROYUKI、TAJIMA, KAYOKO、OSADA, MAKOTO、TSUCHIYA, TAKASHI

  DOI：——

  日期：——
• SAWANISHI, HIROYUKI;TAJIMA, KAYOKO;TSUCHIYA, TAKASHI, CHEM. AND PHARM. BULL., 35,(1987) N 8, 3175-3181
  作者：SAWANISHI, HIROYUKI、TAJIMA, KAYOKO、TSUCHIYA, TAKASHI

  DOI：——

  日期：——