3-[2-(2,6-Difluoro-phenylamino)-pyrimidin-4-yl]-2-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-[2-(2,6-Difluoro-phenylamino)-pyrimidin-4-yl]-2-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one
• 英文别名: 7-[2-(2,6-difluoroanilino)pyrimidin-4-yl]-6-(4-fluorophenyl)-2,3-dihydro-1H-pyrazolo[1,2-a]pyrazol-5-one
• 化学式: C₂₂H₁₆F₃N₅O
• 分子量: 423.397
• InChiKey: RTEPGYYCYOJXTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  61.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(methylsulfanyl)pyrimidine-4-carbonyl chloride 在 Oxone 、 sodium hydroxide 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.58h， 生成 3-[2-(2,6-Difluoro-phenylamino)-pyrimidin-4-yl]-2-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one
  参考文献：
  名称：

  Development of Orally Bioavailable Bicyclic Pyrazolones as Inhibitors of Tumor Necrosis Factor-α Production

  摘要：

  2-Aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-alpha) inhibitors, which contain a novel bicyclic pyrazolope core, are described. Many showed low-nanomolar activity against lipopolysaccharide-induced TNF-alpha production in monocytic cells. Secondary screening data are presented for the pyrimidinyl bicyclic pyrazolones. Several of these analogues showed good oral bioavailability in rat and efficacy in the rat iodoacetate in vivo model.

  DOI：

  10.1021/jm049968m

文献信息

• 6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines
  申请人：The Procter & Gamble Company

  公开号：US20040038971A1

  公开（公告）日：2004-02-26

  The present invention relates to compounds which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: 1 wherein R 1 is substituted aryl; R 4 is substituted or unsubstituted aryl or heteroaryl.

  本发明涉及能够预防炎症细胞因子的细胞外释放的化合物，这些化合物包括所有对映异构体和二面体异构体形式以及其药学上可接受的盐，其化学式为：1其中R1为取代芳基；R4为取代或未取代的芳基或杂环芳基。
• 6,7-DIHYDRO-5H-PYRAZOLO[1,2-A] PYRAZOL-1-ONES WHICH CONTROL INFLAMMATORY CYTOKINES
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP1539761A1

  公开（公告）日：2005-06-15
• 6,7-DIHYDRO-5H-PYRAZOLO¬1,2-A PYRAZOL-1-ONES WHICH CONTROL INFLAMMATORY CYTOKINES
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP1539761B1

  公开（公告）日：2009-04-22
• US6849627B2
  申请人：——

  公开号：US6849627B2

  公开（公告）日：2005-02-01
• [EN] 6,7-DIHYDRO-5H-PYRAZOLO[1,2-a]PYRAZOL-1-ONES WHICH CONTROL INFLAMMATORY CYTOKINES<br/>[FR] DERIVES DE 6,7-DIHYDRO-5H-PYRAZOLO[1,2-A]PYRAZOL-1-ONES CONTROLANT LES CYTOKINES INFLAMMATOIRES
  申请人：PROCTER & GAMBLE

  公开号：WO2004026878A1

  公开（公告）日：2004-04-01

  The present invention relates to compounds which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula (I) wherein R1 is substituted aryl; R4 is substituted or unsubstituted aryl or heteroaryl.