2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-5-(trifluoromethyl)pyridine | 1355052-60-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-5-(trifluoromethyl)pyridine
• 英文别名: 2-[4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]-5-(trifluoromethyl)pyridine；2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]-5-(trifluoromethyl)pyridine
• CAS: 1355052-60-6
• 化学式: C₁₈H₁₉BF₃NO₃
• 分子量: 365.16
• InChiKey: GVLWZZFHUAKXSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.19
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-5-(trifluoromethyl)pyridine 在 bis-triphenylphosphine-palladium(II) chloride sodium carbonate 、 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 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 26.0h， 生成 methyl (2S)-2-[[6-[4-[5-(trifluoromethyl)pyridin-2-yl]oxyphenyl]pyridine-2-carbonyl]amino]propanoate
  参考文献：
  名称：

  [EN] PYRIDINE COMPOUNDS AS SODIUM CHANNEL BLOCKERS
  [FR] COMPOSÉS PYRIDINES COMME BLOQUEURS DES CANAUX SODIQUES

  摘要：

  该发明涉及公式I的取代吡啶化合物：(I)或其药学上可接受的盐、前药或溶剂化合物，其中A1、X、A2、R1a、R1b、R1c、G和z的定义如规范中所述。该发明还涉及利用公式I的化合物治疗对钠通道阻滞有响应的疾病。本发明的化合物特别适用于治疗疼痛。

  公开号：

  WO2012007836A1
• 作为产物：
  描述：

  2-碘-5-三氟甲基吡啶 在 2-吡啶甲酸 、 potassium phosphate 、 copper(l) iodide 、 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 potassium acetate 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-5-(trifluoromethyl)pyridine
  参考文献：
  名称：

  Discovery, Synthesis, and Optimization of Antimalarial 4(1H)-Quinolone-3-Diarylethers

  摘要：

  The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by a novel chemical route and assessed for in vitro activity against multidrug resistant strains of Plasmodium falciparum and against malaria infections in mice. Here we describe the pathway to discovery of a potent class of orally active antimalarial 4(1H)-quinolone-3-diarylethers. The initial prototype, ELQ-233, exhibited low nanomolar IC50 values against all tested strains including clinical isolates harboring resistance to atovaquone. ELQ-271 represented the next critical step in the iterative optimization process, as it was stable to metabolism and highly effective in vivo. Continued analoging revealed that the substitution pattern on the benzenoid ring of the quinolone core significantly influenced reactivity with the host enzyme. This finding led to the rational design of highly selective ELQs with outstanding oral efficacy against murine malaria that is superior to established antimalarials chloroquine and atovaquone.

  DOI：

  10.1021/jm500147k

文献信息

• TRIAZINE CARBOXAMIDES AS SODIUM CHANNEL BLOCKERS
  申请人：Purdue Pharma L.P.

  公开号：US20140249128A1

  公开（公告）日：2014-09-04

  The present disclosure provides substituted triazine carboxamides of Formula I: and the pharmaceutically acceptable salts and solvates thereof, wherein A 1 , X, A 2 , E, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.

  本公开提供了式I的替代三嗪羧酰胺化合物：和其药用可接受的盐和溶剂，其中A1、X、A2、E和Z的定义如规范中所述。本公开还涉及使用式I的化合物来治疗对钠通道阻滞有响应的疾病。本公开的化合物特别适用于治疗疼痛。
• [EN] PYRIDINE COMPOUNDS AS SODIUM CHANNEL BLOCKERS<br/>[FR] COMPOSÉS PYRIDINES COMME BLOQUEURS DES CANAUX SODIQUES
  申请人：PURDUE PHARMA LP

  公开号：WO2012007836A1

  公开（公告）日：2012-01-19

  The invention relates to substituted pyridine compounds of Formula I: (I) or a pharmaceutically acceptable salt, prodrug, or solvate thereof, wherein A1, X, A2, R1a, R1b, R1c, G, and z are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain.

  该发明涉及公式I的取代吡啶化合物：(I)或其药学上可接受的盐、前药或溶剂化合物，其中A1、X、A2、R1a、R1b、R1c、G和z的定义如规范中所述。该发明还涉及利用公式I的化合物治疗对钠通道阻滞有响应的疾病。本发明的化合物特别适用于治疗疼痛。
• Discovery, Synthesis, and Optimization of Antimalarial 4(1<i>H</i>)-Quinolone-3-Diarylethers
  作者：Aaron Nilsen、Galen P. Miley、Isaac P. Forquer、Michael W. Mather、Kasiram Katneni、Yuexin Li、Sovitj Pou、April M. Pershing、Allison M. Stickles、Eileen Ryan、Jane Xu Kelly、J. Stone Doggett、Karen L. White、David J. Hinrichs、Rolf W. Winter、Susan A. Charman、Lev N. Zakharov、Ian Bathurst、Jeremy N. Burrows、Akhil B. Vaidya、Michael K. Riscoe

  DOI：10.1021/jm500147k

  日期：2014.5.8

  The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by a novel chemical route and assessed for in vitro activity against multidrug resistant strains of Plasmodium falciparum and against malaria infections in mice. Here we describe the pathway to discovery of a potent class of orally active antimalarial 4(1H)-quinolone-3-diarylethers. The initial prototype, ELQ-233, exhibited low nanomolar IC50 values against all tested strains including clinical isolates harboring resistance to atovaquone. ELQ-271 represented the next critical step in the iterative optimization process, as it was stable to metabolism and highly effective in vivo. Continued analoging revealed that the substitution pattern on the benzenoid ring of the quinolone core significantly influenced reactivity with the host enzyme. This finding led to the rational design of highly selective ELQs with outstanding oral efficacy against murine malaria that is superior to established antimalarials chloroquine and atovaquone.