methyl 2-chloro-3-(cyanomethyl)benzoate | 1123582-06-8

• 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: methyl 2-chloro-3-(cyanomethyl)benzoate
• CAS: 1123582-06-8
• 化学式: C₁₀H₈ClNO₂
• 分子量: 209.632
• InChiKey: WVFIHDPLIIBBFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-chloro-3-(cyanomethyl)benzoate 在 氯化亚砜 、 lithium hydroxide monohydrate 、 水 、 铁粉 、 sodium hydride 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 、 calcium chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 61.08h， 生成 N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2-fluorophenyl}-2-chloro-3-(1-cyanocyclopropyl)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
• 作为产物：
  描述：

  2-氯-3-甲基苯甲酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 反应 16.0h， 生成 methyl 2-chloro-3-(cyanomethyl)benzoate
  参考文献：
  名称：

  EP3889156

  摘要：

  公开号：

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。
• NITROGEN-CONTAINING HETEROCYCLIC COMPOUND AND COMPOSITION THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
  申请人：Shanghai Pharmaceuticals Holding Co., Ltd.

  公开号：EP3889156A1

  公开（公告）日：2021-10-06

  Disclosed by the present invention are a nitrogen-containing heterocyclic compound, and a composition thereof, a preparation method therefor and an application thereof. The structure of the nitrogen-containing heterocyclic compound according to the present invention is shown in Formula I. The nitrogen-containing heterocyclic compound according to the present invention or a pharmaceutically acceptable salt thereof has better inhibitory activity on p38 protein kinase and/or higher bioavailability. In addition, the preparation method is simple.

  本发明公开了一种含氮杂环化合物及其组合物、制备方法和应用。根据本发明的含氮杂环化合物的结构如式 I 所示。根据本发明的含氮杂环化合物或其药学上可接受的盐对 p38 蛋白激酶具有更好的抑制活性和/或更高的生物利用度。此外，制备方法简单。
• 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
• Nitrogen-containing Heterocyclic Compound and Composition Thereof, Preparation Method Therefor, and Application Thereof
  申请人：SHANGHAI PHARMACEUTICALS HOLDING CO., LTD.

  公开号：US20220048915A1

  公开（公告）日：2022-02-17

  Disclosed by the present invention are a nitrogen-containing heterocyclic compound, and a composition thereof, a preparation method therefor and an application thereof. The structure of the nitrogen-containing heterocyclic compound according to the present invention is shown in Formula I. The nitrogen-containing heterocyclic compound according to the present invention or a pharmaceutically acceptable salt thereof has better inhibitory activity on p38 protein kinase and/or higher bioavailability. In addition, the preparation method is simple.