6-chloro-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonyl chloride | 5791-09-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 6-chloro-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonyl chloride
• 英文别名: 6-chloro-3-oxo-4H-1,4-benzoxazine-7-sulfonyl chloride
• CAS: 5791-09-3
• 化学式: C₈H₅Cl₂NO₄S
• mdl: MFCD07774179
• 分子量: 282.104
• InChiKey: YIYLLOZTGTXGTM-UHFFFAOYSA-N

物化性质

• 熔点：
  258 °C (decomp)
• 沸点：
  483.8±45.0 °C(Predicted)
• 密度：
  1.674±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonyl chloride 在 硼烷四氢呋喃络合物 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 19.17h， 生成 6-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide
  参考文献：
  名称：

  [EN] DIHYDROBENZOXAZINE AND TETRAHYDROQUINOXALINE SODIUM CHANNEL INHIBITORS
  [FR] INHIBITEURS DES CANAUX SODIQUES DE TYPE DIHYDROBENZOXAZINE ET TÉTRAHYDROQUINOXALINE

  摘要：

  本发明提供了式I的化合物或其药学上可接受的盐，这些化合物是电压门控钠通道的抑制剂，特别是Nav 1.7。这些化合物对于治疗可通过抑制钠通道治疗的疾病，如疼痛障碍，是有用的。还提供了含有本发明化合物的药物组合物。

  公开号：

  WO2013122897A1

文献信息

• DIHYDROBENZOXAZINE AND TETRAHYDROQUINOXALINE SODIUM CHANNEL INHIBITORS
  申请人：AMGEN INC.

  公开号：US20150057271A1

  公开（公告）日：2015-02-26

  The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. 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.

  本发明提供了I式化合物或其药学上可接受的盐，其是电压门控钠通道的抑制剂，特别是Nav1.7。这些化合物对于治疗可通过钠通道抑制治疗的疾病如疼痛症状是有用的。还提供了含有本发明化合物的药物组合物。
• Dihydrobenzoxazine and tetrahydroquinoxaline sodium channel inhibitors
  申请人：AMGEN INC.

  公开号：US09346798B2

  公开（公告）日：2016-05-24

  The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. 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.

  本发明提供了I式化合物或其药学上可接受的盐，这些化合物是电压门控钠通道的抑制剂，特别是Nav 1.7。这些化合物对于治疗可通过抑制钠通道治疗的疾病，如疼痛障碍，是有用的。还提供了含有本发明化合物的制药组合物。
• Curable composition including epoxy resin and curable solid filler
  申请人：3M INNOVATIVE PROPERTIES COMPANY

  公开号：US11078358B2

  公开（公告）日：2021-08-03

  The present disclosure provides a curable composition. The curable composition includes a liquid epoxy resin component a curative component, and a curable resin filler component. At least a portion of curable resin filler is dispersed in the liquid epoxy resin and solid at about 25° C. According to various examples, the curable composition can produce a film having good tackiness and improved handling characteristics. Additionally, according to some examples, a cured product of the curable composition can have a Wet Glass Transition Temperature and a Dry Glass Transition Temperature that are substantially the same.

  本公开提供了一种可固化组合物。固化组合物包括液态环氧树脂组分、固化剂组分和固化树脂填料组分。至少有一部分可固化树脂填料分散在液态环氧树脂中，并在约 25°C 时固化。根据不同的实例，该可固化组合物可以生产出具有良好粘性和更佳处理特性的薄膜。此外，根据某些实例，可固化组合物的固化产物的湿玻璃转化温度和干玻璃转化温度基本相同。
• The discovery of benzoxazine sulfonamide inhibitors of Na V 1.7: Tools that bridge efficacy and target engagement
  作者：Daniel S. La、Emily A. Peterson、Christiane Bode、Alessandro A. Boezio、Howard Bregman、Margaret Y. Chu-Moyer、James Coats、Erin F. DiMauro、Thomas A. Dineen、Bingfan Du、Hua Gao、Russell Graceffa、Hakan Gunaydin、Angel Guzman-Perez、Robert Fremeau、Xin Huang、Christopher Ilch、Thomas J. Kornecook、Charles Kreiman、Joseph Ligutti、Min-Hwa Jasmine Lin、Jeff S. McDermott、Isaac Marx、David J. Matson、Stefan I. McDonough、Bryan D. Moyer、Hanh Nho Nguyen、Kristin Taborn、Violeta Yu、Matthew M. Weiss

  DOI：10.1016/j.bmcl.2017.05.070

  日期：2017.8

  The voltage-gated sodium channel Na(V)1.7 has received much attention from the scientific community due to compelling human genetic data linking gain-and loss-of-function mutations to pain phenotypes. Despite this genetic validation of Na(V)1.7 as a target for pain, high quality pharmacological tools facilitate further understanding of target biology, establishment of target coverage requirements and subsequent progression into the clinic. Within the sulfonamide class of inhibitors, reduced potency on rat Na(V)1.7 versus human Na(V)1.7 was observed, rendering in vivo rat pharmacology studies challenging. Herein, we report the discovery and optimization of novel benzoxazine sulfonamide inhibitors of human, rat and mouse Na(V)1.7 which enabled pharmacological assessment in traditional behavioral rodent models of pain and in turn, established a connection between formalin-induced pain and histamine-induced pruritus in mice. The latter represents a simple and efficient means of measuring target engagement. (C) 2017 Elsevier Ltd. All rights reserved.
• 2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase
  作者：Martin J. Walsh、Kyle R. Brimacombe、Henrike Veith、James M. Bougie、Thomas Daniel、William Leister、Lewis C. Cantley、William J. Israelsen、Matthew G. Vander Heiden、Min Shen、Douglas S. Auld、Craig J. Thomas、Matthew B. Boxer

  DOI：10.1016/j.bmcl.2011.08.114

  日期：2011.11

  Compared to normal differentiated cells, cancer cells have altered metabolic regulation to support biosynthesis and the expression of the M2 isozyme of pyruvate kinase (PKM2) plays an important role in this anabolic metabolism. While the M1 isoform is a highly active enzyme, the alternatively spliced M2 variant is considerably less active and expressed in tumors. While the exact mechanism by which decreased pyruvate kinase activity contributes to anabolic metabolism remains unclear, it is hypothesized that activation of PKM2 to levels seen with PKM1 may promote a metabolic program that is not conducive to cell proliferation. Here we report the third chemotype in a series of PKM2 activators based on the 2-oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamide scaffold. The synthesis, structure activity relationships, selectivity and notable physiochemical properties are described. Published by Elsevier Ltd.