3-(4-bromo-2-fluorophenoxy)-2-(4-methanesulfonylphenyl)-6-methylpyran-4-one | 361381-15-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(4-bromo-2-fluorophenoxy)-2-(4-methanesulfonylphenyl)-6-methylpyran-4-one
• 英文别名: 3-(4-Bromo-2-fluoro-phenoxy)-2-(4-methanesulfonyl-phenyl)-6-methyl-pyran-4-one；3-(4-bromo-2-fluorophenoxy)-6-methyl-2-(4-methylsulfonylphenyl)pyran-4-one
• CAS: 361381-15-9
• 化学式: C₁₉H₁₄BrFO₅S
• 分子量: 453.286
• InChiKey: SGZPDQDNNJQFNW-UHFFFAOYSA-N

物化性质

• 熔点：
  215 °C
• 沸点：
  609.8±55.0 °C(Predicted)
• 密度：
  1.560±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  四甲基锡 、 3-(4-bromo-2-fluorophenoxy)-2-(4-methanesulfonylphenyl)-6-methylpyran-4-one 在 palladium diacetate 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 以64%的产率得到3-(2-fluoro-4-methylphenoxy)-2-(4-methanesulfonylphenyl)-6-methylpyran-4-one
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2-Phenylpyran-4-ones:  A New Class of Orally Active Cyclooxygenase-2 Inhibitors

  摘要：

  A series of 2-phenylpyran-4-ones were prepared and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). Extensive structure-activity relationship work was carried out within this series, and a number of potent and selective COX-2 inhibitors were identified. Compounds having a p-methylsulfone group at the 2-phenyl ring showed the best COX-2 inhibitory activity. The introduction of a substituted phenoxy ring at position 3 enhanced both the in vitro and in vivo activity within the series. A selected group of 3-phenoxypyran-4-ones exhibited excellent activity in an experimental model of pyresis. The in vivo antiinflammatory activity of these compounds was confirmed with the evaluation of their antiarthritic and analgesic effectiveness. Moreover, their pharmacokinetic profile in rats is compatible with a once a day administration by oral route in humans. Within this novel series, compounds 21, 31, 34, and 35 have been selected for further preclinical. and clinical evaluation.

  DOI：

  10.1021/jm049882t
• 作为产物：
  描述：

  4-溴-2-氟苯酚 在 Oxone 、 PPA 、 四丁基硫酸氢铵 、 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 24.0h， 生成 3-(4-bromo-2-fluorophenoxy)-2-(4-methanesulfonylphenyl)-6-methylpyran-4-one
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2-Phenylpyran-4-ones:  A New Class of Orally Active Cyclooxygenase-2 Inhibitors

  摘要：

  A series of 2-phenylpyran-4-ones were prepared and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). Extensive structure-activity relationship work was carried out within this series, and a number of potent and selective COX-2 inhibitors were identified. Compounds having a p-methylsulfone group at the 2-phenyl ring showed the best COX-2 inhibitory activity. The introduction of a substituted phenoxy ring at position 3 enhanced both the in vitro and in vivo activity within the series. A selected group of 3-phenoxypyran-4-ones exhibited excellent activity in an experimental model of pyresis. The in vivo antiinflammatory activity of these compounds was confirmed with the evaluation of their antiarthritic and analgesic effectiveness. Moreover, their pharmacokinetic profile in rats is compatible with a once a day administration by oral route in humans. Within this novel series, compounds 21, 31, 34, and 35 have been selected for further preclinical. and clinical evaluation.

  DOI：

  10.1021/jm049882t

文献信息

• 2-Phenylpyran-4-one derivatives
  申请人：——

  公开号：US20030232880A1

  公开（公告）日：2003-12-18

  The present invention relates to 2-(4-sulphonylphenyl)pyran-4-one derivatives of general formula 1 processes for their preparation, pharmaceutical compositions containing them, and their medical uses.

  本发明涉及通式为1的2-(4-磺酰基苯基)吡喃-4-酮衍生物的制备方法、含有它们的制药组合物以及它们的医药用途。
• Combinations comprising DHODH inhibitors and COX inhibitors
  申请人：Almirall, S.A.

  公开号：EP2444086A1

  公开（公告）日：2012-04-25

  Combinations comprising (a) DHODH inhibitors and (b) COX inhibitors and their use in treating skin diseases or disorders are disclosed.

  本研究公开了由(a) DHODH 抑制剂和(b) COX 抑制剂组成的组合物及其在治疗皮肤疾病或失调中的用途。
• 2-PHENYLPYRAN-4-ONE DERIVATIVES
  申请人：Almirall Prodesfarma AG

  公开号：EP1263751B1

  公开（公告）日：2004-06-16
• PHARMACEUTICAL COMPOSITIONS COMPRISING DIMETHYL FUMARATE
  申请人：Almirall S.A.

  公开号：EP3079666A1

  公开（公告）日：2016-10-19
• Pharmaceutical Compositions Comprising Dimethyl Fumarate
  申请人：Almirall, S.A.

  公开号：US20200197348A1

  公开（公告）日：2020-06-25

  Pharmaceutical compositions are described comprising (a) dimethyl fumarate, (b) a diluent selected from monosaccharides, disaccharides, starch and starch derivatives, calcium and magnesium inorganic salts, sugar alcohols, and mixtures thereof, (c) microcrystalline cellulose and (d) croscarmellose sodium, wherein the dimethyl fumarate is not covered with a gastroresistant coating. These compositions are intended for the treatment of some inflammatory autoimmune diseases or disorders.