(R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline | 959996-46-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline
• 英文别名: ELND007；Unii-vku3jvl7UC；(4R)-4-cyclopropyl-8-fluoro-5-[6-(trifluoromethyl)pyridin-3-yl]sulfonyl-1,4-dihydropyrazolo[4,3-c]quinoline
• CAS: 959996-46-4
• 化学式: C₁₉H₁₄F₄N₄O₂S
• 分子量: 438.405
• InChiKey: LBJYPLZODCWHKE-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 乙酸乙酯 为溶剂， 反应 1.5h， 生成 (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline
  参考文献：
  名称：

  Fused, Tricyclic Sulfonamide Inhibitors of Gamma Secretase

  摘要：

  该发明提供了公式I的化合物： 或其药用盐，其中R 1 ，R 2 和A、B和C环如本文所定义。公式I的化合物在治疗或预防认知障碍，如阿尔茨海默病方面是有用的。该发明还涵盖了包括公式I的化合物或盐的药物组合物，制备所需化合物的方法，以及使用公式I的化合物或盐治疗认知障碍，如阿尔茨海默病的方法。

  公开号：

  US20080021056A1

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。
• Fused, tricyclic sulfonamide inhibitors of gamma secretase
  申请人：Elan Pharmaceuticals Inc.

  公开号：EP2450358A1

  公开（公告）日：2012-05-09

  The invention provides compounds of formula I: or pharmaceutically salts thereof, where R1, R2 and the A, B, and C-rings are as defined herein. Compounds of formula I are useful in treating or preventing cognitive disorders, such as Alzheimer's disease. The invention also encompasses pharmaceutical compositions comprising compounds or salts of formula I, methods of preparing the desired compunds, and methods of treating cognitive disorders, such as Alzheimer's disease, using the compounds or salts of formula I.

  本发明提供了式 I 的化合物： 或其药用盐，其中 R1、R2 和 A、B 及 C 环如本文所定义。式 I 的化合物可用于治疗或预防认知障碍，如阿尔茨海默病。本发明还包括包含式 I 化合物或盐的药物组合物、制备所需组合物的方法以及使用式 I 化合物或盐治疗认知障碍（如阿尔茨海默病）的方法。
• METHODS FOR DETERMINING CELLS SUCH AS CIRCULATING CANCER OR FETAL CELLS
  申请人：Analiza, Inc.

  公开号：EP3702783A1

  公开（公告）日：2020-09-02

  Some embodiments of the present invention generally relate to devices and methods for determining and/or isolating cells. For example, one aspect is generally directed to methods and devices for detecting, identifying, counting, and/or potentially sorting cells of interest in blood or other biological sample. In some embodiments, blood samples (or other biological fluids) may be treated with signaling entities, such as pH-sensitive entities, that change color or otherwise produce a signal in suitable internal environments. For example, certain cells, such as cancer or fetal cells, may have differences in intracellular pH compared to other cells, which can be detected using pH-sensitive entities. In certain embodiments, the cells may be sorted based on such signaling entities; for example, illumination of cells in a suitable machine for sorting cells (e. g., using fluorescent light) may allow determination of the cells, which may also be recovered or isolated for further manipulation in some cases.

  本发明的一些实施方案一般涉及用于确定和/或分离细胞的装置和方法。例如，一个方面一般涉及用于检测、识别、计数和/或可能分选血液或其他生物样本中相关细胞的方法和装置。在某些实施方案中，血液样本（或其他生物液体）可以用信号实体（如 pH 敏感实体）处理，这些实体会变色或在合适的内部环境中产生信号。例如，某些细胞（如癌细胞或胎儿细胞）与其他细胞相比，细胞内 pH 值可能存在差异，可使用 pH 值敏感实体进行检测。在某些实施方案中，可根据此类信号实体对细胞进行分选；例如，在用于分选细胞的合适机器中对细胞进行照射（如使用荧光灯），可对细胞进行测定，在某些情况下，还可对细胞进行回收或分离，以便进一步操作。
• Devices and methods for determining and/or isolating cells such as circulating cancer or fetal cells
  申请人：Analiza, Inc.

  公开号：US10928405B2

  公开（公告）日：2021-02-23

  Some embodiments of the present invention generally relate to devices and methods for determining and/or isolating cells. For example, one aspect is generally directed to methods and devices for detecting, identifying, counting, and/or potentially sorting cells of interest in blood or other biological sample. In some embodiments, blood samples (or other biological fluids) may be treated with signaling entities, such as pH-sensitive entities, that change color or otherwise produce a signal in suitable internal environments. For example, certain cells, such as cancer or fetal cells, may have differences in intracellular pH compared to other cells, which can be detected using pH-sensitive entities. In certain embodiments, the cells may be sorted based on such signaling entities; for example, illumination of cells in a suitable machine for sorting cells (e.g., using fluorescent light) may allow determination of the cells, which may also be recovered or isolated for further manipulation in some cases.

  本发明的一些实施方案一般涉及用于确定和/或分离细胞的装置和方法。例如，一个方面一般涉及用于检测、识别、计数和/或可能分选血液或其他生物样本中相关细胞的方法和装置。在某些实施方案中，血液样本（或其他生物液体）可以用信号实体（如 pH 敏感实体）处理，这些实体会变色或在合适的内部环境中产生信号。例如，某些细胞（如癌细胞或胎儿细胞）与其他细胞相比，细胞内 pH 值可能存在差异，可使用 pH 值敏感实体进行检测。在某些实施方案中，可根据此类信号实体对细胞进行分选；例如，在用于分选细胞的合适机器中对细胞进行照射（如使用荧光灯），可对细胞进行测定，在某些情况下，还可对细胞进行回收或分离，以便进一步操作。
• 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.