N-(3-(2-bromo-2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide | 1622082-84-1

• 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: N-(3-(2-bromo-2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide
• 英文别名: N-[3-[2-bromo-2-(2-chloropyrimidin-4-yl)acetyl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide
• CAS: 1622082-84-1
• 化学式: C₁₈H₁₀BrClF₃N₃O₃S
• 分子量: 520.714
• InChiKey: SJWGEWAEPJZUFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  97.4
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(3-(2-bromo-2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide 在 盐酸 、 2,2,2-三氟乙醇 作用下， 以 水 为溶剂， 生成 B-Raf IN 18
  参考文献：
  名称：

  Development of potent B-RafV600E inhibitors containing an arylsulfonamide headgroup

  摘要：

  A potent series of inhibitors against the B-RafV600E kinase have been developed that show excellent activity in cellular assays and good oral bioavailability in rats. The key structural features of the series are an arylsulfonamide headgroup, a thiazole core, and a fluorine ortho to the sulfonamide nitrogen. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.021
• 作为产物：
  描述：

  3-溴-2-氟苯甲酸 在 吡啶 、 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 N-溴代丁二酰亚胺(NBS) 、 硫酸 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 3.25h， 生成 N-(3-(2-bromo-2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide
  参考文献：
  名称：

  Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors

  摘要：

  Hyperactive signaling of the MAP kinase pathway resulting from the constitutively active B-Raf(v600E) mutated enzyme has been observed in a number of human tumors, including melanomas. Herein we report the discovery and biological evaluation of GSK2118436, a selective inhibitor of Raf kinases with potent in vitro activity in oncogenic B-Raf-driven melanoma and colorectal carcinoma cells and robust in vivo antitumor and pharmacodynamic activity in mouse models of B-Raf(v600E) human melanoma. GSK2118436 was identified as a development candidate, and early clinical results have shown significant activity in patients with B-Raf mutant melanoma.

  DOI：

  10.1021/ml4000063

文献信息

• [EN] COMBINATIONS OF AN ANTI-PD-L1 ANTIBODY AND A MEK INHIBITOR AND/OR A BRAF INHIBITOR<br/>[FR] COMBINAISONS D'UN ANTICORPS ANTI-PD-L1 ET D'UN INHIBITEUR DE MEK ET/OU D'UN INHIBITEUR DE BRAF
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2014195852A1

  公开（公告）日：2014-12-11

  A novel combination comprising the MEK inhibitor N-3-[3-cyclopropyl-5-(2-fluoro- 4-iodo-phenylamino)6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3- d]pyrimidin-1 -yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, and/or a B-Raf inhibitor, particularly N-3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1 - dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, and an anti-PD-L1 antibody; pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and/or B-Raf and/or neutralizing or inhibiting the interaction between PD-L1 and its receptor, e.g. PD-1, is beneficial, eg. cancer.

  一种新型组合物，包括MEK抑制剂N-3-[3-环丙基-5-(2-氟-4-碘苯胺基)6,8-二甲基-2,4,7-三氧代-3,4,6,7-四氢-2H-吡啶并[4,3-d]嘧啶-1-基]苯基}乙酰胺，或其药用可接受的盐或溶剂，和/或B-Raf抑制剂，特别是N-3-[5-(2-氨基-4-嘧啶基)-2-(1,1-二甲基乙基)-1,3-噻唑-4-基]-2-氟苯基}-2,6-二氟苯磺酰胺或其药用可接受的盐，以及一种抗PD-L1抗体；包括这些组合物的药物组合物和使用这些组合物和组合物治疗MEK和/或B-Raf的抑制和/或PD-L1及其受体之间的中和或抑制相互作用有益的疾病条件的方法，例如癌症。
• 苯磺酰胺噁唑和噻唑激酶抑制剂
  申请人：通化济达医药有限公司

  公开号：CN103965180B

  公开（公告）日：2016-09-07

  本发明属于医药技术领域，具体涉及通式(Ⅰ)所示的苯磺酰胺噁唑和噻唑激酶抑制剂、其药学上可接受的盐或其立体异构体，其中环A、R1、R2、R3、X、m、n和p如说明书中所定义。本发明还涉及这些化合物的制备方法，含有这些化合物的药物制剂和药物组合物，以及该化合物、其药学上可接受的盐或其立体异构体在制备治疗和/或预防由b‑RAF突变引起的癌症相关或非癌症相关疾病的药物中的应用。
• SULFONAMIDO DERIVATIVES AS CYCLIN-DEPENDENT KINASE 2 INHIBITORS
  申请人：NiKang Therapeutics, Inc.

  公开号：US20230303509A1

  公开（公告）日：2023-09-28

  The present disclosure provides certain sulfonamido derivatives that are Cyclin-dependent kinase 2 (CDK2) inhibitors of Formula (I): for the treatment of diseases treatable by inhibition of CDK2. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.