6-(2,4-difluorobenzyl)-8-methyl-2-(methylsulfonyl)pyrido[2,3-d]pyrimidin-7(8H)-one | 1280218-25-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 6-(2,4-difluorobenzyl)-8-methyl-2-(methylsulfonyl)pyrido[2,3-d]pyrimidin-7(8H)-one
• 英文别名: 6-[(2,4-Difluorophenyl)methyl]-8-methyl-2-methylsulfonylpyrido[2,3-d]pyrimidin-7-one
• CAS: 1280218-25-8
• 化学式: C₁₆H₁₃F₂N₃O₃S
• 分子量: 365.36
• InChiKey: RBUXBZUGTLGCCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  88.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-(2,4-difluorobenzyl)-8-methyl-2-(methylsulfonyl)pyrido[2,3-d]pyrimidin-7(8H)-one 在 盐酸 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 乙醚 为溶剂， 反应 1.0h， 生成 6-(2,4-difluorobenzyl)-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 40.25h， 生成 6-(2,4-difluorobenzyl)-8-methyl-2-(methylsulfonyl)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

文献信息

• Discovery of 6-(2,4-Difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8<i>H</i>-pyrido[2,3-<i>d</i>]pyrimidin-7-one (Pamapimod) and 6-(2,4-Difluorophenoxy)-8-methyl-2-(tetrahydro-2<i>H</i>-pyran-4-ylamino)pyrido[2,3-<i>d</i>]pyrimidin-7(8<i>H</i>)-one (R1487) as Orally Bioavailable and Highly Selective Inhibitors of p38α Mitogen-Activated Protein Kinase
  作者：David M. Goldstein、Michael Soth、Tobias Gabriel、Nolan Dewdney、Andreas Kuglstatter、Humberto Arzeno、Jeffrey Chen、William Bingenheimer、Stacie A. Dalrymple、James Dunn、Robert Farrell、Sandra Frauchiger、JoAnn La Fargue、Manjiri Ghate、Bradford Graves、Ronald J. Hill、Fujun Li、Renee Litman、Brad Loe、Joel McIntosh、Daniel McWeeney、Eva Papp、Jaehyeon Park、Harlan F. Reese、Richard T. Roberts、David Rotstein、Bong San Pablo、Keshab Sarma、Martin Stahl、Man-Ling Sung、Rebecca T. Suttman、Eric B. Sjogren、Yunchou Tan、Alejandra Trejo、Mary Welch、Paul Weller、Brian R. Wong、Hasim Zecic

  DOI：10.1021/jm101423y

  日期：2011.4.14

  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.