8-methyl-2-methylsulfonyl-6-phenoxy-8H-pyrido[2,3-d]pyrimidin-7-one | 449808-46-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 8-methyl-2-methylsulfonyl-6-phenoxy-8H-pyrido[2,3-d]pyrimidin-7-one
• 英文别名: 6-phenoxy-8-methyl-2-(methylsulfonyl) pyrido[2,3-d]pyrimidin-7(8H)-one；6-Phenoxy-8-methyl-2-(methylsulfonyl)pyrido[2,3-d]pyrimidin-7(8h)-one；8-methyl-2-methylsulfonyl-6-phenoxypyrido[2,3-d]pyrimidin-7-one
• CAS: 449808-46-2
• 化学式: C₁₅H₁₃N₃O₄S
• 分子量: 331.352
• InChiKey: KODHFNKJIPBAEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  23
• 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：
  6

反应信息

• 作为反应物：
  描述：

  8-methyl-2-methylsulfonyl-6-phenoxy-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-(phenoxy)-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 58.25h， 生成 8-methyl-2-methylsulfonyl-6-phenoxy-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
• 作为试剂：
  描述：

  6-(2-fluorophenoxy)-8-methyl-2-methylsulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one 、 氨 在 氮气 、 SiO2 、 8-methyl-2-methylsulfonyl-6-phenoxy-8H-pyrido[2,3-d]pyrimidin-7-one 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 4.0h， 以provided 0.33 g of the amine (Mass spec. M+1=287, MP=240.8-242.6° C.)的产率得到2-amino-6-(2-fluorophenoxy)-8-methyl-pyrido[2,3-d]pyrimidin-7(8H)-one
  参考文献：
  名称：

  6-Substituted pyrido-pyrimidines

  摘要：

  本发明提供公式I和II的化合物：1其中R1、R3、W、Z、X1、X2、Ar1、R8和R9如本文所定义，以及其制备方法和中间体以及它们的用途。

  公开号：

  US20040116698A1

文献信息

• 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
• US7449581B2
  申请人：——

  公开号：US7449581B2

  公开（公告）日：2008-11-11
• [EN] 6-SUBSTITUTED PYRIDO-PYRIMIDINES<br/>[FR] PYRIDO-PYRIMIDINES SUBSTITUEES EN POSITION 6
  申请人：HOFFMANN LA ROCHE

  公开号：WO2002064594A2

  公开（公告）日：2002-08-22

  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, processes and intermediates for their preparation and their use for the treatment of p38 mediated disorders.