2,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(pyridin-2-ylsulfonylamino)benzamide | 1186608-22-9

• 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: 2,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(pyridin-2-ylsulfonylamino)benzamide
• CAS: 1186608-22-9
• 化学式: C₁₉H₁₄F₂N₆O₄S
• 分子量: 460.421
• InChiKey: GBQVAOYSISRAJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  147
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,6-二氟-3-硝基苯甲酸 在 吡啶 、 tin(II) chloride dihdyrate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 2,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(pyridin-2-ylsulfonylamino)benzamide
  参考文献：
  名称：

  Pyrazolopyridine inhibitors of B-RafV600E. Part 2: Structure–activity relationships

  摘要：

  Structure-activity relationships around a novel series of B-Raf(V600E) inhibitors are reported. The enzymatic and cellular potencies of inhibitors derived from two related hinge-binding groups were compared and 3-methoxypyrazolopyridine proved to be superior. The 3-alkoxy group of lead B-Raf(V600E) inhibitor 1 was extended and minimally affected potency. The propyl sulfonamide tail of compound 1, which occupies the small lipophilic pocket formed by an outward shift of the alpha C-helix, was expanded to a series of arylsulfonamides. X-ray crystallography revealed that this lipophilic pocket unexpectedly enlarges to accommodate the bulkier aryl group. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.097

文献信息

• [EN] PYRAZOLE [3, 4-B] PYRIDINE RAF INHIBITORS<br/>[FR] INHIBITEURS DE RAF DE PYRAZOLE[3,4-B]PYRIDINE
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2009111279A1

  公开（公告）日：2009-09-11

  Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  公式I的化合物对于抑制Raf激酶很有用。本文揭示了利用公式I的化合物及其立体异构体、互变异构体、前药和药学上可接受的盐，在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗此类疾病或相关病理条件的方法。
• PYRAZOLE [3, 4-B] PYRIDINE RAF INHIBITORS
  申请人：Ahrendt Kateri A.

  公开号：US20110092479A1

  公开（公告）日：2011-04-21

  Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  公式I的化合物对于抑制Raf激酶非常有用。本文揭示了使用公式I及其立体异构体、互变异构体、前药和药学上可接受的盐，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗相关病理状况的方法。
• PYRAZOLE [3, 4-B]PYRIDINE RAF INHIBITORS
  申请人：Array Biopharma, Inc.

  公开号：EP2265610B1

  公开（公告）日：2012-12-12
• US8394795B2
  申请人：——

  公开号：US8394795B2

  公开（公告）日：2013-03-12
• Pyrazolopyridine inhibitors of B-RafV600E. Part 2: Structure–activity relationships
  作者：Steve Wenglowsky、Kateri A. Ahrendt、Alex J. Buckmelter、Bainian Feng、Susan L. Gloor、Stefan Gradl、Jonas Grina、Joshua D. Hansen、Ellen R. Laird、Paul Lunghofer、Simon Mathieu、David Moreno、Brad Newhouse、Li Ren、Tyler Risom、Joachim Rudolph、Jeongbeob Seo、Hillary L. Sturgis、Walter C. Voegtli、Zhaoyang Wen

  DOI：10.1016/j.bmcl.2011.06.097

  日期：2011.9

  Structure-activity relationships around a novel series of B-Raf(V600E) inhibitors are reported. The enzymatic and cellular potencies of inhibitors derived from two related hinge-binding groups were compared and 3-methoxypyrazolopyridine proved to be superior. The 3-alkoxy group of lead B-Raf(V600E) inhibitor 1 was extended and minimally affected potency. The propyl sulfonamide tail of compound 1, which occupies the small lipophilic pocket formed by an outward shift of the alpha C-helix, was expanded to a series of arylsulfonamides. X-ray crystallography revealed that this lipophilic pocket unexpectedly enlarges to accommodate the bulkier aryl group. (C) 2011 Elsevier Ltd. All rights reserved.