4-(2,2-dibromovinyl)-5,7-dimethyl-1-tosyl-1H-indole | 1481633-78-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(2,2-dibromovinyl)-5,7-dimethyl-1-tosyl-1H-indole
• 英文别名: 4-(2,2-Dibromovinyl)-5,7-dimethyl-1-tosyl-1H-indole；4-(2,2-dibromoethenyl)-5,7-dimethyl-1-(4-methylphenyl)sulfonylindole
• CAS: 1481633-78-6
• 化学式: C₁₉H₁₇Br₂NO₂S
• 分子量: 483.223
• InChiKey: ZXFCZURLIYEHBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(2,2-dibromovinyl)-5,7-dimethyl-1-tosyl-1H-indole 在 三乙烯二胺 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 反应 20.0h， 生成 2-((5,7-dimethyl-1H-indol-4-yl)methyl)-1H-benzo[d]imidazole
  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：

  5,7-dimethyl-4-nitro-1-tosyl-1 H-indole 在 盐酸 、 正丁基锂 、 溶剂黄146 、 三苯基膦 、 锌 、 sodium nitrite 作用下， 以 甲醇 、 正己烷 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-(2,2-dibromovinyl)-5,7-dimethyl-1-tosyl-1H-indole
  参考文献：
  名称：

  Complement pathway modulators and uses thereof

  摘要：

  本发明提供了一种化合物I的方法：制造本发明化合物的方法及其治疗用途。本发明还提供了一种药理活性剂的组合以及一种药物组成。

  公开号：

  US20130296377A1

文献信息

• Complement pathway modulators and uses thereof
  申请人：ADAMS Christopher Michael

  公开号：US20130296377A1

  公开（公告）日：2013-11-07

  The present invention provides a compound of formula I: a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种化合物I的方法：制造本发明化合物的方法及其治疗用途。本发明还提供了一种药理活性剂的组合以及一种药物组成。
• COMPLEMENT PATHWAY MODULATORS AND USES THEREOF
  申请人：Novartis AG

  公开号：EP2855456B1

  公开（公告）日：2017-03-29
• US9056874B2
  申请人：——

  公开号：US9056874B2

  公开（公告）日：2015-06-16
• [EN] COMPLEMENT PATHWAY MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DES VOIES DU COMPLÉMENT ET LEURS UTILISATIONS
  申请人：NOVARTIS AG

  公开号：WO2013164802A1

  公开（公告）日：2013-11-07

  The present invention provides a compound of formula I: (I) a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
• 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.