ELND006 | 959997-22-9

• 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: ELND006
• 英文别名: (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline；(R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo(4,3-c)quinoline；(4R)-4-cyclopropyl-7,8-difluoro-5-[4-(trifluoromethyl)phenyl]sulfonyl-1,4-dihydropyrazolo[4,3-c]quinoline
• CAS: 959997-22-9
• 化学式: C₂₀H₁₄F₅N₃O₂S
• 分子量: 455.408
• InChiKey: XODSHWXKSMPDRP-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  74.4
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (R)-1-tert-butyl-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline 在 甲酸 、 水 作用下， 反应 1.5h， 以99%的产率得到ELND006
  参考文献：
  名称：

  [EN] PROCESS FOR THE PRODUCTION OF FUSED, TRICYCLIC SULFONAMIDES
  [FR] PROCÉDÉ DE PRODUCTION DE SULFONAMIDES TRICYCLIQUES FUSIONNÉS

  摘要：

  公开号：

  WO2010111418A3

文献信息

• Process for the Production of Fused, Tricyclic Sulfonamides
  申请人：Dappen Michael S.

  公开号：US20110034691A1

  公开（公告）日：2011-02-10

  The present invention provides methods, i.e., scalable or large-scale processes for the production of fused, tricyclic sulfonamido analogs, such as substituted or unsubstituted 5-(aryl-sulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolines and 5-(heteroaryl-sulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolines. Exemplary methods of the invention include an intra-molecular cyclization step, in which a carbon-nitrogen bond is formed, and which employs a copper-based catalyst that contains at least one organic ligand, such as DMEDA. The invention further provides compounds, which are useful as intermediates in the methods of the invention.

  本发明提供了一种生产熔合的、三环磺酰胺类似物的可扩展或大规模过程的方法，例如取代或未取代的5-（芳基磺酰基）-4,5-二氢-1H-吡唑并[4,3-c]喹啉和5-（杂环芳基磺酰基）-4,5-二氢-1H-吡唑并[4,3-c]喹啉。本发明的示例方法包括一种分子内环化步骤，其中形成一种碳-氮键，并使用至少含有一种有机配体（例如DMEDA）的铜基催化剂。本发明还提供了化合物，其在本发明的方法中作为中间体有用。
• Discovery of (<i>R</i>)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1<i>H</i>-pyrazolo[4,3-<i>c</i>]quinoline (ELND006) and (<i>R</i>)-4-Cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2<i>H</i>-pyrazolo[4,3-<i>c</i>]quinoline (ELND007): Metabolically Stable γ-Secretase Inhibitors that Selectively Inhibit the Production of Amyloid-β over Notch
  作者：Gary Probst、Danielle L. Aubele、Simeon Bowers、Darren Dressen、Albert W. Garofalo、Roy K. Hom、Andrei W. Konradi、Jennifer L. Marugg、Matthew N. Mattson、Martin L. Neitzel、Chris M. Semko、Hing L. Sham、Jenifer Smith、Minghua Sun、Anh P. Truong、Xiaocong M. Ye、Ying-zi Xu、Michael S. Dappen、Jacek J. Jagodzinski、Pamela S. Keim、Brian Peterson、Lee H. Latimer、David Quincy、Jing Wu、Erich Goldbach、Daniel K. Ness、Kevin P. Quinn、John-Michael Sauer、Karina Wong、Hongbin Zhang、Wes Zmolek、Elizabeth F. Brigham、Dora Kholodenko、Kang Hu、Grace T. Kwong、Michael Lee、Anna Liao、Ruth N. Motter、Patricia Sacayon、Pamela Santiago、Christopher Willits、Frédérique Bard、Michael P. Bova、Susanna S. Hemphill、Lam Nguyen、Lany Ruslim、Kevin Tanaka、Pearl Tanaka、William Wallace、Ted A. Yednock、Guriqbal S. Basi

  DOI：10.1021/jm301741t

  日期：2013.7.11

  Herein, we describe our strategy to design metabolically stable gamma-secretase inhibitors which are selective for inhibition of A beta generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006) and 34 (ELND007) both entered human clinical trials. The in vitro and in vivo characteristics for these two compounds are described. A comparison of inhibition of A beta generation in vivo between 30, 34, Semagacestat 41, Begacestat 42, and Avagacestat 43 in mice is made. 30 lowered A in the CSF of healthy human volunteers.
• PROCESS FOR THE PRODUCTION OF FUSED, TRICYCLIC SULFONAMIDES
  申请人：Elan Pharmaceuticals Inc.

  公开号：EP2411388A2

  公开（公告）日：2012-02-01
• [EN] PROCESS FOR THE PRODUCTION OF FUSED, TRICYCLIC SULFONAMIDES<br/>[FR] PROCÉDÉ DE PRODUCTION DE SULFONAMIDES TRICYCLIQUES FUSIONNÉS
  申请人：ELAN PHARM INC

  公开号：WO2010111418A3

  公开（公告）日：2010-12-02