(4,5-dihydro-1H-imidazol-2-yl)-(4-methyl-naphthalen-1-yl)-amine | 36314-68-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (4,5-dihydro-1H-imidazol-2-yl)-(4-methyl-naphthalen-1-yl)-amine
• 英文别名: N-(4-methylnaphthalen-1-yl)-4,5-dihydro-1H-imidazol-2-amine；(4,5-dihydro-1H-imidazol-2-yl)-(4-methyl-naphthalen-1-yl)-amine；2-<4-Methyl-naphthyl-(1)-amino>-1,3-diazacyclopenten
• CAS: 36314-68-8
• 化学式: C₁₄H₁₅N₃
• 分子量: 225.293
• InChiKey: LAMODLLJXBPJBV-UHFFFAOYSA-N

物化性质

• 沸点：
  389.3±35.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  17.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  36.42
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (4,5-dihydro-1H-imidazol-2-yl)-(4-methyl-naphthalen-1-yl)-amine 在 溴 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以35%的产率得到N-(2-bromo-4-methylnaphthalen-1-yl)-4,5-dihydro-1H-imidazol-2-amine
  参考文献：
  名称：

  Discovery of 4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a Diverse Array of Complement Mediated Diseases

  摘要：

  The alternative pathway (AP) of the complement system is a key contributor to the pathogenesis of several human diseases including age-related macular degeneration, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and various glomerular diseases. The serine protease factor B (FB) is a key node in the AP and is integral to the formation of C3 and C5 convertase. Despite the prominent role of FB in the AP, selective orally bioavailable inhibitors, beyond our own efforts, have not been reported previously. Herein we describe in more detail our efforts to identify FB inhibitors by high-throughput screening (HTS) and leveraging insights from several X-ray cocrystal structures during optimization efforts. This work culminated in the discovery of LNP023 (41), which is currently being evaluated clinically in several diverse AP mediated indications.

  DOI：

  10.1021/acs.jmedchem.9b01870
• 作为产物：
  描述：

  4-甲基萘-1-胺 、 4,5-二氢-1H-咪唑-2-磺酸 以 异丁醇 为溶剂， 反应 4.0h， 以23%的产率得到(4,5-dihydro-1H-imidazol-2-yl)-(4-methyl-naphthalen-1-yl)-amine
  参考文献：
  名称：

  Discovery of 4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a Diverse Array of Complement Mediated Diseases

  摘要：

  The alternative pathway (AP) of the complement system is a key contributor to the pathogenesis of several human diseases including age-related macular degeneration, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and various glomerular diseases. The serine protease factor B (FB) is a key node in the AP and is integral to the formation of C3 and C5 convertase. Despite the prominent role of FB in the AP, selective orally bioavailable inhibitors, beyond our own efforts, have not been reported previously. Herein we describe in more detail our efforts to identify FB inhibitors by high-throughput screening (HTS) and leveraging insights from several X-ray cocrystal structures during optimization efforts. This work culminated in the discovery of LNP023 (41), which is currently being evaluated clinically in several diverse AP mediated indications.

  DOI：

  10.1021/acs.jmedchem.9b01870