5-氯-6-氟吡啶-3-基硼酸 | 1366482-32-7

• 物质功能分类: 有机原料 - 有机氟化合物 - 氟吡啶系列
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 5-氯-6-氟吡啶-3-基硼酸
• 中文别名: 5-氯-6-氟吡啶-3-硼酸
• 英文名称: (5-chloro-6-fluoropyridin-3-yl)boronic acid
• 英文别名: (5-Chloro-6-fluoropyridin-3-YL)boronic acid
• CAS: 1366482-32-7
• 化学式: C₅H₄BClFNO₂
• 分子量: 175.355
• InChiKey: YYFMQBOVWLWZQO-UHFFFAOYSA-N

物化性质

• 沸点：
  341.2±52.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.45
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  53.4
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312+P330,P302+P352,P304+P340+P312,P305+P351+P338,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  5-氯-6-氟吡啶-3-基硼酸 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 (R)-1-((3-chloro-5-(pyrazolo[1,5-a]pyrimidin-7-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine
  参考文献：
  名称：

  [EN] BIARYL KINASE INHIBITORS
  [FR] INHIBITEURS BIARYLES DE KINASES

  摘要：

  本公开涉及公式（I）的联苯化合物，可以抑制AAK1（适配器相关激酶1），包括这种化合物的组合物以及它们用于治疗疼痛、阿尔茨海默病、帕金森病和精神分裂症等的用途。

  公开号：

  WO2017059080A1

文献信息

• [EN] BIARYL KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASES À BASE DE BIARYLE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2017059085A1

  公开（公告）日：2017-04-06

  The present disclosure is directed to biaryl compounds of formula (I) which can inhibit AAKl (adaptor associated kinase 1), compositions comprising such compounds and their use for treating e.g. pain, Alzheimer's disease, Parkinson's disease and schizophrenia.

  本公开涉及式(I)的双芳基化合物，该化合物能够抑制AAK1（适配器相关激酶1），包含此类化合物的组合物以及它们用于治疗例如疼痛、阿尔茨海默病、帕金森病和精神分裂症。
• Discovery of potent, selective, and metabolically stable 4-(pyridin-3-yl)cinnolines as novel phosphodiesterase 10A (PDE10A) inhibitors
  作者：Essa Hu、Roxanne K. Kunz、Shannon Rumfelt、Ning Chen、Roland Bürli、Chun Li、Kristin L. Andrews、Jiandong Zhang、Samer Chmait、Jeffrey Kogan、Michelle Lindstrom、Stephen A. Hitchcock、James Treanor

  DOI：10.1016/j.bmcl.2012.01.086

  日期：2012.3

  We report the discovery of 6,7-dimethoxy-4-(pyridin-3-yl)cinnolines as novel inhibitors of phosphodiesterase 10A (PDE10A). Systematic examination and analyses of structure–activity-relationships resulted in single digit nM potency against PDE10A. X-ray co-crystal structure revealed the mode of binding in the enzyme’s catalytic domain and the source of selectivity against other PDEs. High in vivo clearance

  我们报告发现6,7-二甲氧基-4-（吡啶-3-基）cinnolines作为磷酸二酯酶10A（PDE10A）的新型抑制剂。对结构-活性关系的系统检查和分析导致抗PDE10A的位数为nM。X射线共晶体结构揭示了酶催化结构域中的结合模式以及对其他PDE的选择性来源。借助代谢物鉴定（ID）研究解决了大鼠体内高清除率的问题。这些发现共同产生了化合物39，它是一种有前途的有效PDE10A抑制剂，在大鼠中具有良好的体内代谢稳定性，并在啮齿动物行为模型中具有功效。
• [EN] BIARYL ACYL-SULFONAMIDE COMPOUNDS AS SODIUM CHANNEL INHIBITORS<br/>[FR] COMPOSÉS D'ACYLSULFONAMIDE DE BIARYLE EN TANT QU'INHIBITEURS DES CANAUX SODIQUES
  申请人：AMGEN INC

  公开号：WO2015051043A1

  公开（公告）日：2015-04-09

  The present invention provides compounds of Formula (Ia), and pharmaceutically acceptable salts thereof. The compounds are useful as inhibitors of voltage-gated sodium channels, in particular Nav 1.7. (Ia); as described in the specification. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention, as well as intermediates and processes useful for making the compounds.

  本发明提供了化合物(Ia)及其药用可接受的盐。这些化合物可用作电压门控钠通道的抑制剂，特别是Nav 1.7。（Ia）；如规范中所述。这些化合物可用于治疗通过抑制钠通道可治疗的疾病，如疼痛性疾病。还提供了含有本发明化合物的药物组合物，以及用于制备这些化合物的中间体和工艺。
• Biaryl Acyl-Sulfonamide Compounds as Sodium Channel Inhibitors
  申请人：AMEGEN INC.

  公开号：US20160214971A1

  公开（公告）日：2016-07-28

  The present invention provides compounds of Formula (Ia), and pharmaceutically acceptable salts thereof. The compounds are useful as inhibitors of voltage-gated sodium channels, in particular Nav 1.7. as described in the specification. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention, as well as intermediates and processes useful for making the compounds.

  本发明提供了公式（Ia）的化合物及其药学上可接受的盐。这些化合物可用作电压门控钠通道的抑制剂，特别是Nav 1.7，如规范中所述。这些化合物可用于治疗可通过抑制钠通道治疗的疾病，例如疼痛障碍。还提供了含有本发明化合物的制药组合物，以及制造这些化合物的中间体和工艺。
• 1,2,4-Triazolsulfone: A novel isosteric replacement of acylsulfonamides in the context of Na V 1.7 inhibition
  作者：Alessandro A. Boezio、Kristin Andrews、Christiane Boezio、Margaret Chu-Moyer、Katrina W. Copeland、Erin F. DiMauro、Robert S. Foti、Robert T. Fremeau、Hua Gao、Stephanie Geuns-Meyer、Russell F. Graceffa、Hakan Gunaydin、Hongbing Huang、Daniel S. La、Joseph Ligutti、Bryan D. Moyer、Emily A. Peterson、Violeta Yu、Matthew M. Weiss

  DOI：10.1016/j.bmcl.2018.04.035

  日期：2018.6

  Recently, the identification of several classes of aryl sulfonamides and acyl sulfonamides that potently inhibit Na(v)1.7 and demonstrate high levels of selectivity over other Na-v isoforms have been reported. The fully ionizable nature of these inhibitors has been shown to be an important part of the pharmacophore for the observed potency and isoform selectivity. The requirement of this functionality, however, has presented challenges associated with optimization toward inhibitors with drug-like properties and minimal off-target activity. In an effort to obviate these challenges, we set out to develop an orally bioavailable, selective Na(v)1.7 inhibitor, lacking these acidic functional groups. Herein, we report the discovery of a novel series of inhibitors wherein a triazolesulfone has been designed to serve as a bioisostere for the acyl sulfonamide. This work culminated in the delivery of a potent series of inhibitors which demonstrated good levels of selectivity over Na v 1.5 and favorable pharmacokinetics in rodents. (C) 2018 Elsevier Ltd. All rights reserved.