6-(2,4-difluorophenoxy)-2-methylsulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one | 1280218-26-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(2,4-difluorophenoxy)-2-methylsulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one
• CAS: 1280218-26-9
• 化学式: C₁₄H₉F₂N₃O₄S
• 分子量: 353.306
• InChiKey: SQTBTHQSUMKEOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-氨基四氢吡喃 、 6-(2,4-difluorophenoxy)-2-methylsulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one 以 N-甲基吡咯烷酮 为溶剂， 反应 0.08h， 以49%的产率得到6-(2,4-difluorophenoxy)-8H-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one
  参考文献：
  名称：

  Discovery of 6-(2,4-Difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (Pamapimod) and 6-(2,4-Difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as Orally Bioavailable and Highly Selective Inhibitors of p38α Mitogen-Activated Protein Kinase

  摘要：

  The development of a new series of p38 alpha inhibitors resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. The original lead, an lck inhibitor that also potently inhibited p38a, was a screening hit from our kinase inhibitor library. This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties.

  DOI：

  10.1021/jm101423y
• 作为产物：
  描述：

  4-氨基-2-甲巯基嘧啶-5-甲醛 在 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 6-(2,4-difluorophenoxy)-2-methylsulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Discovery of 6-(2,4-Difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (Pamapimod) and 6-(2,4-Difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as Orally Bioavailable and Highly Selective Inhibitors of p38α Mitogen-Activated Protein Kinase

  摘要：

  The development of a new series of p38 alpha inhibitors resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. The original lead, an lck inhibitor that also potently inhibited p38a, was a screening hit from our kinase inhibitor library. This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties.

  DOI：

  10.1021/jm101423y

文献信息

• US7348331B2
  申请人：——

  公开号：US7348331B2

  公开（公告）日：2008-03-25