N-(2-cyano-4-fluoro-3-(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yloxy)phenyl)propane-1-sulfonamide | 1396310-66-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(2-cyano-4-fluoro-3-(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yloxy)phenyl)propane-1-sulfonamide
• 英文别名: N-[2-cyano-4-fluoro-3-(3-methyl-4-oxoquinazolin-6-yl)oxyphenyl]propane-1-sulfonamide
• CAS: 1396310-66-9
• 化学式: C₁₉H₁₇FN₄O₄S
• 分子量: 416.433
• InChiKey: QBAKJEJGYGSTPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,3,6-三氟苯腈 、 6-羟基-3-甲基喹唑啉-4(3h)-酮 在 sodium hydride 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2-cyano-4-fluoro-3-(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yloxy)phenyl)propane-1-sulfonamide
  参考文献：
  名称：

  [EN] HETEROCYCLIC SULFONAMIDES AS RAF INHIBITORS
  [FR] SULFONAMIDES HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE RAF

  摘要：

  化合物的化学式（I）对于抑制Raf激酶很有用。本文披露了使用化合物的方法（I），立体异构体，互变异构体及其药用可接受的盐，用于体外、体内和体内诊断、预防或治疗哺乳动物细胞中的这类疾病，或相关的病理状况。

  公开号：

  WO2012118492A1

文献信息

• [EN] HETEROCYCLIC SULFONAMIDES AS RAF INHIBITORS<br/>[FR] SULFONAMIDES HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE RAF
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2012118492A1

  公开（公告）日：2012-09-07

  Compounds of Formula (I) are useful for inhibition of Raf kinases. Methods of using compounds of Formula (I), stereoisomers, tautomers 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.

  化合物的化学式（I）对于抑制Raf激酶很有用。本文披露了使用化合物的方法（I），立体异构体，互变异构体及其药用可接受的盐，用于体外、体内和体内诊断、预防或治疗哺乳动物细胞中的这类疾病，或相关的病理状况。
• [EN] NEW METHYLQUINAZOLINONE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE MÉTHYLQUINAZOLINONE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2021116055A1

  公开（公告）日：2021-06-17

  The invention provides a novel compound having the general formula (I) (I), or a pharmaceutically acceptable salt thereof. The compound of formula (I) can be used as a medicament.

  该发明提供了一种具有一般式(I) (I)或其药学上可接受的盐的新化合物。式(I)的化合物可用作药物。
• [EN] NEW SOLID FORMS OF (3R)-N-[2-CYANO-4-FLUORO-3-(3-METHYL-4-OXO-QUINAZOLIN-6-YL)OXY-PHENYL]-3-FLUORO-PYRROLIDINE-1-SULFONAMIDE<br/>[FR] NOUVELLES FORMES SOLIDES DE (3R)-N-[2-CYANO-4-FLUORO-3-(3-MÉTHYL-4-OXO-QUINAZOLIN-6-YL)OXY-PHÉNYL]-3-FLUORO-PYRROLIDINE-1-SULFONAMIDE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2022258584A1

  公开（公告）日：2022-12-15

  The present invention provides solid forms of (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide and solvates thereof, as well as therapeutic uses and processes to manufacture the new solid forms.

  本发明提供了(3R)-N-[2-氰基-4-氟-3-(3-甲基-4-氧基-喹唑啉-6-基)氧基-苯基]-3-氟-吡咯烷-1-磺酰胺及其溶剂结晶体固体形式，以及其治疗用途和制造新固体形式的过程。
• [EN] COMBINATION OF A PARTICULAR BRAF INHIBITOR (PARADOX BREAKER) AND A PD-1 AXIS BINDING ANTAGONIST FOR USE IN THE TREATMENT OF CANCER<br/>[FR] ASSOCIATION D'UN INHIBITEUR DE BRAF PARTICULIER ("PARADOX BREAKER") ET D'UN ANTAGONISTE DE LIAISON À L'AXE PD-1 POUR UNE UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：HOFFMANN LA ROCHE

  公开号：WO2022258600A1

  公开（公告）日：2022-12-15

  The present invention is directed to a combination of the BRAF inhibitor N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy- phenyl]-3-fluoro-pyrrolidine-l-sulfonamide or a pharmaceutically acceptable salt or solvate thereof with a PD-1 axis binding antagonist, and to the use of the combination as a medicament, in particular for the therapeutic and/or prophylactic treatment of cancer.

  本发明涉及一种BRAF抑制剂N-[2-氰基-4-氟-3-(3-甲基-4-氧-喹唑啉-6-基)氧基苯基]-3-氟-吡咯烷-1-磺酰胺或其药学上可接受的盐或溶剂与PD-1轴结合拮抗剂的组合物，并将该组合物用作药物，特别用于治疗和/或预防癌症。
• Highly potent and selective 3-N-methylquinazoline-4(3H)-one based inhibitors of B-RafV600E kinase
  作者：Steve Wenglowsky、Li Ren、Jonas Grina、Joshua D. Hansen、Ellen R. Laird、David Moreno、Victoria Dinkel、Susan L. Gloor、Gregg Hastings、Sumeet Rana、Kevin Rasor、Hillary L. Sturgis、Walter C. Voegtli、Guy Vigers、Brandon Willis、Simon Mathieu、Joachim Rudolph

  DOI：10.1016/j.bmcl.2014.03.007

  日期：2014.4

  Herein we describe the design of a novel series of ATP competitive B-Raf inhibitors via structure-based methods. These 3-N-methylquinazoline-4(3H)-one based inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 16, a potent, selective and orally available agent with excellent pharmacokinetic properties and robust tumor growth inhibition in xenograft studies. Our work also demonstrates that by replacing an aryl amide with an aryl sulfonamide, a multikinase inhibitor such as AZ-628, can be converted to a selective B-Raf inhibitor, a finding that should have broad application in kinase drug discovery. (C) 2014 Elsevier Ltd. All rights reserved.