6-(2,4-difluorophenoxy)-2-(2-hydroxy-1,1-dimethylethylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one | 759451-95-1

• 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-(2-hydroxy-1,1-dimethylethylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one
• 英文别名: 6-(2,4-Difluorophenoxy)-2-(2-hydroxy-1,1-dimethyl-ethylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one；6-(2,4-difluorophenoxy)-2-[(1-hydroxy-2-methylpropan-2-yl)amino]-8-methylpyrido[2,3-d]pyrimidin-7-one
• CAS: 759451-95-1
• 化学式: C₁₈H₁₈F₂N₄O₃
• 分子量: 376.363
• InChiKey: JKNVMEDXAYWIMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  87.6
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-(2,4-difluorophenoxy)-2-(2-hydroxy-1,1-dimethylethylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one 在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 1.0h， 以2.5 g的产率得到6-(2,4-difluorophenoxy)-2-(2-hydroxy-1,1-dimethylethylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one hydrochloride
  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-甲胺基-2-甲硫基-5-嘧啶甲酸乙酯 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 甲酸 、 双氧水 、 potassium carbonate 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 二氯甲烷 、 水 为溶剂， 反应 42.75h， 生成 6-(2,4-difluorophenoxy)-2-(2-hydroxy-1,1-dimethylethylamino)-8-methyl-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

• 6-Substituted pyrido-pyrimidines
  申请人：Chen Jeffrey Jian

  公开号：US20070135458A1

  公开（公告）日：2007-06-14

  The present invention provides compounds of the Formula I and II: wherein R 1 , R 3 , W, Z, X 1 , X 2 , Ar 1 , R 8 and R 9 are as defined herein, and methods and intermediates for their preparation and uses thereof.

  本发明提供了公式I和II的化合物：其中R1、R3、W、Z、X1、X2、Ar1、R8和R9如本文所定义，以及它们的制备方法和中间体以及它们的用途。
• US7169794B2
  申请人：——

  公开号：US7169794B2

  公开（公告）日：2007-01-30
• US7449581B2
  申请人：——

  公开号：US7449581B2

  公开（公告）日：2008-11-11