6-(2,4-difluorophenoxy)-2-methylsulfanyl-8-(3-methylsulfanylpropyl)-8H-pyrido[2,3-d]pyrimidin-7-one | 1280218-35-0

• 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-methylsulfanyl-8-(3-methylsulfanylpropyl)-8H-pyrido[2,3-d]pyrimidin-7-one
• CAS: 1280218-35-0
• 化学式: C₁₈H₁₇F₂N₃O₂S₂
• 分子量: 409.481
• InChiKey: RSHGZLDFYRIYLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  27.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  57.01
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  6-(2,4-difluorophenoxy)-2-methylsulfanyl-8-(3-methylsulfanylpropyl)-8H-pyrido[2,3-d]pyrimidin-7-one 在 Oxone 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 6-(2,4-difluorophenoxy)-2-methanesulfonyl-8-(3-methanesulfonylpropyl)-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
• 作为产物：
  描述：

  4-氨基-2-甲巯基嘧啶-5-甲醛 在 三丁基膦 、 potassium carbonate 、 偶氮二甲酸二乙酯 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 168.0h， 生成 6-(2,4-difluorophenoxy)-2-methylsulfanyl-8-(3-methylsulfanylpropyl)-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