6-(2-fluorophenoxy)-4-methylpyridin-3-amine | 307309-26-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(2-fluorophenoxy)-4-methylpyridin-3-amine
• 英文别名: 6-(2-Fluorophenoxy)-4-methylpyridin-3-amine
• CAS: 307309-26-8
• 化学式: C₁₂H₁₁FN₂O
• 分子量: 218.231
• InChiKey: WAVJHELNNJFOHK-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-(2-fluorophenoxy)-4-methylpyridin-3-amine 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 5-azido-2-(2-fluorophenoxy)-4-methylpyridine
  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：

  2-溴-4-甲基-5-氨基吡啶 、 2-氟苯酚 在 copper(l) iodide 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以88%的产率得到6-(2-fluorophenoxy)-4-methylpyridin-3-amine
  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

• AMINOPYRAZOLE DERIVATIVES
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP3312172A1

  公开（公告）日：2018-04-25

  An objective of the present invention is to provide low-molecular-weight compounds that can inhibit Src family kinases. The present invention relates to compounds represented by general formula (I) or pharmacologically acceptable salts thereof. In the formula, Ar1 is optionally substituted C6-10 arylene or 5- to 10-membered heteroarylene, and Ar2 is optionally substituted C6-10 aryl or 5- to 10-membered heteroaryl. R1 and R2 are defined as described in the specification.

  本发明的目的是提供可抑制 Src 家族激酶的低分子量化合物。本发明涉及通式（I）所代表的化合物或其药理学上可接受的盐类。式中，Ar1为任选取代的C6-10芳基或5-10元杂芳基，Ar2为任选取代的C6-10芳基或5-10元杂芳基。R1 和 R2 的定义如说明书所述。
• Aminopyrazole derivatives
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US10479780B2

  公开（公告）日：2019-11-19

  An objective of the present invention is to provide low-molecular-weight compounds that can inhibit Src family kinases. The present invention relates to compounds represented by general formula (I) or pharmacologically acceptable salts thereof. In the formula, Ar1 is optionally substituted C6-10 arylene or 5- to 10-membered heteroarylene, and Ar2 is optionally substituted C6-10 aryl or 5- to 10-membered heteroaryl. R1 and R2 are defined as described in the specification.

  本发明的目的是提供可抑制 Src 家族激酶的低分子量化合物。本发明涉及通式（I）所代表的化合物或其药理学上可接受的盐类。式中，Ar1为任选取代的C6-10芳基或5-10元杂芳基，Ar2为任选取代的C6-10芳基或5-10元杂芳基。R1 和 R2 的定义如说明书所述。
• [EN] AMINOPYRAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'AMINOPYRAZOLE<br/>[JA] アミノピラゾール誘導体
  申请人：CHUGAI PHARMACEUTICAL CO LTD

  公开号：WO2016204261A1

  公开（公告）日：2016-12-22

  本発明は、Ｓｒｃファミリーキナーゼを阻害することができる低分子化合物を提供することを課題とする。本発明は、下記一般式（Ｉ）： で表される化合物、またはその薬理学的に許容される塩に関する。式中、Ａｒ１は置換されていてもよいＣ６－１０アリーレンまたは５～１０員ヘテロアリーレンであり、Ａｒ２は置換されていてもよいＣ６－１０アリールまたは５～１０員ヘテロアリールである。Ｒ１、Ｒ２は明細書に記載の定義と同意義である。
• Hit-to-lead optimization of a latency-associated nuclear antigen inhibitor against Kaposi’s sarcoma-associated herpesvirus infections
  作者：Philine Kirsch、Saskia C. Stein、Aylin Berwanger、Julia Rinkes、Valentin Jakob、Thomas F. Schulz、Martin Empting

  DOI：10.1016/j.ejmech.2020.112525

  日期：2020.9

  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.