3-fluorophenyl 2-(4-methylthiophenyl)(3-pyridyl) ketone | 654059-05-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-fluorophenyl 2-(4-methylthiophenyl)(3-pyridyl) ketone
• 英文别名: Methanone, (3-fluorophenyl)[2-[4-(methylthio)phenyl]-3-pyridinyl]-；(3-fluorophenyl)-[2-(4-methylsulfanylphenyl)pyridin-3-yl]methanone
• CAS: 654059-05-9
• 化学式: C₁₉H₁₄FNOS
• 分子量: 323.391
• InChiKey: XWORUDPRYTWNFO-UHFFFAOYSA-N

物化性质

• 熔点：
  91-92 °C
• 沸点：
  517.5±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  55.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-fluorophenyl 2-(4-methylthiophenyl)(3-pyridyl) ketone 在 potassium hydrogensulfate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以99%的产率得到3-fluorophenyl 2-[(4-methylsulfonyl)phenyl](3-pyridyl) ketone
  参考文献：
  名称：

  3-[4-(Methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) Phenyl Ketone as a Potent and Orally Active Cyclooxygenase-2 Selective Inhibitor:  Synthesis and Biological Evaluation

  摘要：

  Incorporation of a spacer group between the central scaffold and the aryl ring resulted in a new cyclooxygenase-2 (COX-2) selective inhibitor core structure, 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone (20), with COX-2 IC50 = 0.25 mu M and COX-1 IC50 = 14 mu M (human whole blood assay). Compound 20 was orally active in the rat air pouch model of inflammation, inhibiting white blood cell infiltration and COX-2-derived PG production. Our data support the identification of a novel COX-2 selective inhibitor core structure exemplified by 20.

  DOI：

  10.1021/jm0582064
• 作为产物：
  描述：

  间溴氟苯 在 四(三苯基膦)钯 、 碘 、 sodium carbonate 、 magnesium 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 0.25h， 生成 3-fluorophenyl 2-(4-methylthiophenyl)(3-pyridyl) ketone
  参考文献：
  名称：

  3-[4-(Methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) Phenyl Ketone as a Potent and Orally Active Cyclooxygenase-2 Selective Inhibitor:  Synthesis and Biological Evaluation

  摘要：

  Incorporation of a spacer group between the central scaffold and the aryl ring resulted in a new cyclooxygenase-2 (COX-2) selective inhibitor core structure, 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone (20), with COX-2 IC50 = 0.25 mu M and COX-1 IC50 = 14 mu M (human whole blood assay). Compound 20 was orally active in the rat air pouch model of inflammation, inhibiting white blood cell infiltration and COX-2-derived PG production. Our data support the identification of a novel COX-2 selective inhibitor core structure exemplified by 20.

  DOI：

  10.1021/jm0582064

文献信息

• Cyclooxygenase-2 selective inhibitors, compositions and methods of use
  申请人：NitroMed, Inc.

  公开号：US20040072883A1

  公开（公告）日：2004-04-15

  The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  本发明描述了新型环氧合酶2（COX-2）选择性抑制剂和包含至少一种环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及可选地，至少一种捐赠、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮衍生松弛因子水平或是一氧化氮合酶底物的化合物，和/或至少一种治疗剂。本发明还提供了包含至少一种COX-2选择性抑制剂、可选地亚硝化和/或亚硝酰化，以及可选地至少一种一氧化氮给体和/或至少一种治疗剂的新型试剂盒。本发明的新型环氧合酶2选择性抑制剂可选择性地亚硝化和/或亚硝酰化。本发明还提供了治疗炎症、疼痛和发热的方法；用于治疗和/或改善COX-2选择性抑制剂的胃肠道特性；促进伤口愈合的方法；用于治疗和/或预防肾脏和/或呼吸毒性的方法；用于治疗和/或预防由于环氧合酶-2水平升高而引起的其他疾病的方法；以及用于改善COX-2选择性抑制剂的心血管特性的方法。
• CYCLOOXYGENASE- 2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE
  申请人：Nitromed, Inc.

  公开号：EP1542972A2

  公开（公告）日：2005-06-22
• EP1542972A4
  申请人：——

  公开号：EP1542972A4

  公开（公告）日：2008-01-23
• US7244753B2
  申请人：——

  公开号：US7244753B2

  公开（公告）日：2007-07-17
• [EN] CYCLOOXYGENASE- 2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE<br/>[FR] INHIBITEURS SELECTIFS DE LA CYCLO-OXYGENASE-2, COMPOSITIONS ET PROCEDES D'UTILISATION
  申请人：NITROMED INC

  公开号：WO2004010945A2

  公开（公告）日：2004-02-05

  The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium­derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.