6-(4-fluorophenoxy)-8-methyl-2-methylsulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one | 449811-75-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(4-fluorophenoxy)-8-methyl-2-methylsulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one
• 英文别名: 6-(4-fluorophenoxy)-8-methyl-2-(methylsulfonyl) pyrido[2,3-d]pyrimidin-7(8H)-one；6-(4-fluorophenoxy)-8-methyl-2-methylsulfonylpyrido[2,3-d]pyrimidin-7-one
• CAS: 449811-75-0
• 化学式: C₁₅H₁₂FN₃O₄S
• 分子量: 349.342
• InChiKey: QCZSRZUYYORFDG-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：
  0.13
• 拓扑面积：
  97.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-(4-fluorophenoxy)-8-methyl-2-methylsulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one 在 盐酸 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 乙醚 为溶剂， 反应 3.0h， 生成 6-(4-fluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-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 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 26.75h， 生成 6-(4-fluorophenoxy)-8-methyl-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

• 6-Substituted pyrido-pyrimidines
  申请人：——

  公开号：US20030171584A1

  公开（公告）日：2003-09-11

  The present invention provides compounds of the Formula I and II: 1 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.

  本发明提供了化合物I和II的结构：其中R1、R3、W、Z、X1、X2、Ar1、R8和R9如本文所定义，并提供它们的制备方法和中间体以及它们的用途。
• 6-substituted pyrido-pyrimidines
  申请人：Roche Palo Alto LLC

  公开号：US07169794B2

  公开（公告）日：2007-01-30

  The present invention provides compounds of the Formula I and II: wherein R1, R3, W, Z, X1, X2, Ar1, R8 and R9 are as defined herein, and methods and intermediates for their preparation and uses thereof.

  本发明提供了式I和式II的化合物：其中R1，R3，W，Z，X1，X2，Ar1，R8和R9如本文所定义，并提供了它们的制备方法和中间体，以及它们的用途。
• 6-SUBSTITUTED PYRIDO-PYRIMIDINES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1361880A2

  公开（公告）日：2003-11-19
• US6696566B2
  申请人：——

  公开号：US6696566B2

  公开（公告）日：2004-02-24
• US7169794B2
  申请人：——

  公开号：US7169794B2

  公开（公告）日：2007-01-30