2-chloro-4-methylnaphthalen-1-amine | 51670-76-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-chloro-4-methylnaphthalen-1-amine
• 英文别名: 2-Chloro-4-methyl-1-naphthylamine
• CAS: 51670-76-9
• 化学式: C₁₁H₁₀ClN
• mdl: MFCD20542933
• 分子量: 191.66
• InChiKey: HGXKKSNLWFCUBT-UHFFFAOYSA-N

物化性质

• 沸点：
  332.7±27.0 °C(Predicted)
• 密度：
  1.244±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-chloro-4-methylnaphthalen-1-amine 在 2-氯-1,3-二甲基氯化咪唑啉 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 0.5h， 生成 N-(2-chloro-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 在 N-氯代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以46%的产率得到2-chloro-4-methylnaphthalen-1-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

文献信息

• DE2323956
  申请人：——

  公开号：——

  公开（公告）日：——
• METALLKOMPLEXE
  申请人：Merck Patent GmbH

  公开号：EP3044284B1

  公开（公告）日：2019-11-13
• [DE] METALLKOMPLEXE<br/>[EN] METAL COMPLEXES<br/>[FR] COMPLEXES MÉTALLIQUES
  申请人：MERCK PATENT GMBH

  公开号：WO2015036074A1

  公开（公告）日：2015-03-19

  Die vorliegende Erfindung betrifft Metallkomplexe sowie elektronische Vorrichtungen, insbesondere organische Elektrolumineszenzvorrichtungen, enthaltend diese Metallkomplexe.
• Discovery of 4-((2<i>S</i>,4<i>S</i>)-4-Ethoxy-1-((5-methoxy-7-methyl-1<i>H</i>-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
  作者：Nello Mainolfi、Takeru Ehara、Rajeshri G. Karki、Karen Anderson、Aengus Mac Sweeney、Sha-Mei Liao、Upendra A. Argikar、Keith Jendza、Chun Zhang、James Powers、Daniel W. Klosowski、Maura Crowley、Toshio Kawanami、Jian Ding、Myriam April、Cornelia Forster、Michael Serrano-Wu、Michael Capparelli、Rrezarta Ramqaj、Catherine Solovay、Frederic Cumin、Thomas M. Smith、Luciana Ferrara、Wendy Lee、Debby Long、Melissa Prentiss、Andrea De Erkenez、Louis Yang、Fang Liu、Holger Sellner、Finton Sirockin、Eric Valeur、Paulus Erbel、Daniela Ostermeier、Paul Ramage、Bernd Gerhartz、Anna Schubart、Stefanie Flohr、Nathalie Gradoux、Roland Feifel、Barbara Vogg、Christian Wiesmann、Jürgen Maibaum、Jörg Eder、Richard Sedrani、Richard A. Harrison、Muneto Mogi、Bruce D. Jaffee、Christopher M. Adams

  DOI：10.1021/acs.jmedchem.9b01870

  日期：2020.6.11

  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.