2,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide | 1186499-89-7

• 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: 2,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide
• 英文别名: 2,6-difluoro-3-(propylsulfonylamino)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide
• CAS: 1186499-89-7
• 化学式: C₁₇H₁₆F₂N₄O₃S
• 分子量: 394.402
• InChiKey: LVJGJCRNAGZHGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 氯仿 为溶剂， 以82%的产率得到N-(3-bromo-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide
  参考文献：
  名称：

  Pyrazolopyridine Inhibitors of B-Raf^V600E. Part 1: The Development of Selective, Orally Bioavailable, and Efficacious Inhibitors

  摘要：

  The V600E mutation of B-Raf kinase results in constitutive activation of the MAPK signaling pathway and is present in approximately 7% of all cancers. Using structure-based design, a novel series of pyrazolopyridine inhibitors of B-Raf(V600E) was developed. Optimization led to the identification of 3-methoxy pyrazolopyridines 17 and 19, potent, selective, and orally bioavailable agents that inhibited tumor growth in a mouse xenograft model driven by B-Raf(V600E) with no effect on body weight. On the basis of their in vivo efficacy and preliminary safety profiles, 17 and 19 were selected for further preclinical evaluation.

  DOI：

  10.1021/ml200025q
• 作为产物：
  描述：

  5-氨基-7-氮杂吲哚 、 唯罗菲妮中间体 在 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 N,N-二甲基甲酰胺 为溶剂， 以53%的产率得到2,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide
  参考文献：
  名称：

  Pyrazolopyridine Inhibitors of B-Raf^V600E. Part 1: The Development of Selective, Orally Bioavailable, and Efficacious Inhibitors

  摘要：

  The V600E mutation of B-Raf kinase results in constitutive activation of the MAPK signaling pathway and is present in approximately 7% of all cancers. Using structure-based design, a novel series of pyrazolopyridine inhibitors of B-Raf(V600E) was developed. Optimization led to the identification of 3-methoxy pyrazolopyridines 17 and 19, potent, selective, and orally bioavailable agents that inhibited tumor growth in a mouse xenograft model driven by B-Raf(V600E) with no effect on body weight. On the basis of their in vivo efficacy and preliminary safety profiles, 17 and 19 were selected for further preclinical evaluation.

  DOI：

  10.1021/ml200025q

文献信息

• RAF INHIBITOR COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Ahrendt et al. Kateri A.

  公开号：US20110110889A1

  公开（公告）日：2011-05-12

  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.

  式(I)的化合物可用于抑制Raf激酶。本文揭示了使用式(I)的化合物及其立体异构体、互变异构体、前药和药物可接受的盐，在哺乳动物细胞的体外、体内诊断、预防或治疗相关的病理情况的方法。
• Raf inhibitor compounds and methods of use thereof
  申请人：Array BioPharma Inc.

  公开号：US08338452B2

  公开（公告）日：2012-12-25

  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）的化合物及其立体异构体、互变异构体、前药和药物可接受的盐，用于哺乳动物细胞中的体外、体内诊断、预防或治疗这些疾病或相关病理条件的方法。
• US8338452B2
  申请人：——

  公开号：US8338452B2

  公开（公告）日：2012-12-25
• [EN] RAF INHIBITOR COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS INHIBITEURS DE KINASES RAF ET PROCÉDÉS D'UTILISATION
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2009111278A2

  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.
• Pyrazolopyridine Inhibitors of B-Raf^V600E. Part 1: The Development of Selective, Orally Bioavailable, and Efficacious Inhibitors
  作者：Steve Wenglowsky、Li Ren、Kateri A. Ahrendt、Ellen R. Laird、Ignacio Aliagas、Bruno Alicke、Alex J. Buckmelter、Edna F. Choo、Victoria Dinkel、Bainian Feng、Susan L. Gloor、Stephen E. Gould、Stefan Gross、Janet Gunzner-Toste、Joshua D. Hansen、Georgia Hatzivassiliou、Bonnie Liu、Kim Malesky、Simon Mathieu、Brad Newhouse、Nicholas J. Raddatz、Yingqing Ran、Sumeet Rana、Nikole Randolph、Tyler Risom、Joachim Rudolph、Scott Savage、LeAnn T. Selby、Michael Shrag、Kyung Song、Hillary L. Sturgis、Walter C. Voegtli、Zhaoyang Wen、Brandon S. Willis、Richard D. Woessner、Wen-I Wu、Wendy B. Young、Jonas Grina

  DOI：10.1021/ml200025q

  日期：2011.5.12

  The V600E mutation of B-Raf kinase results in constitutive activation of the MAPK signaling pathway and is present in approximately 7% of all cancers. Using structure-based design, a novel series of pyrazolopyridine inhibitors of B-Raf(V600E) was developed. Optimization led to the identification of 3-methoxy pyrazolopyridines 17 and 19, potent, selective, and orally bioavailable agents that inhibited tumor growth in a mouse xenograft model driven by B-Raf(V600E) with no effect on body weight. On the basis of their in vivo efficacy and preliminary safety profiles, 17 and 19 were selected for further preclinical evaluation.