3-(1-cyano-1-methylethyl)-N-[3-({2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)phenyl]benzamide | 1123580-77-7

• 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: 3-(1-cyano-1-methylethyl)-N-[3-({2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)phenyl]benzamide
• 英文别名: 3-(2-cyanopropan-2-yl)-N-[3-[[2-(cyclopropanecarbonylamino)-1,3-benzothiazol-6-yl]oxy]phenyl]benzamide
• CAS: 1123580-77-7
• 化学式: C₂₈H₂₄N₄O₃S
• 分子量: 496.59
• InChiKey: JLENBMPQLPGHFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-[3-(4-aminophenoxy)phenyl]-3-(1-cyano-1-methylethyl)benzamide 在 吡啶 、 4-二甲氨基吡啶 、 溶剂黄146 作用下， 反应 10.75h， 生成 3-(1-cyano-1-methylethyl)-N-[3-({2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)phenyl]benzamide
  参考文献：
  名称：

  Design and Synthesis of Novel DFG-Out RAF/Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Inhibitors. 1. Exploration of [5,6]-Fused Bicyclic Scaffolds

  摘要：

  To develop RAF/VEGFR2 inhibitors that bind to the inactive DFG-out conformation, we conducted structure-based drug design using the X-ray cocrystal structures of BRAF, starting from an imidazo[1,2-b]pyridazine derivative. We designed various [5,6]-fused bicyclic scaffolds (ring A, 1-6) possessing an anilide group that forms two hydrogen bond interactions with Cys532. Stabilizing the planarity of this anilide and the nitrogen atom on the six-membered ring of the scaffold was critical for enhancing BRAF inhibition. The selected [1,3]thiazolo[5,4-b]pyridine derivative 6d showed potent inhibitory activity in both BRAF and VEGFR2. Solid dispersion formulation of 6d (6d-SD) maximized its oral absorption in rats and showed significant suppression of ERK1/2 phosphorylation in an A375 melanoma xenograft model in rats by single administration. Tumor regression (T/C = -7.0%) in twice-daily repetitive studies at a dose of 50 mg/kg in rats confirmed that 6d is a promising RAF/VEGFR2 inhibitor showing potent anticancer activity.

  DOI：

  10.1021/jm300126x

文献信息

• HETEROCYCLIC COMPOUND AND USE THEREOF
  申请人：Hirose Masaaki

  公开号：US20110172245A1

  公开（公告）日：2011-07-14

  Provided is a heterocyclic compound showing strong Raf inhibitory activity. A compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof.

  提供的是一种具有强烈Raf抑制活性的杂环化合物。该化合物由以下式表示：其中每个符号如规范中定义，或其盐。
• Heterocyclic compound and use thereof
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US08324395B2

  公开（公告）日：2012-12-04

  Provided is a heterocyclic compound showing strong Raf inhibitory activity. A compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof.

  提供的是一种具有较强Raf抑制活性的杂环化合物。该化合物由下式所表示：其中每个符号如规范中所定义，或其盐。
• 2-Carbonylaminobenzothiazoles and their use for the prophylaxis and treatment of cancer
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2181987B9

  公开（公告）日：2014-09-03
• US8324395B2
  申请人：——

  公开号：US8324395B2

  公开（公告）日：2012-12-04