6-(2,4-difluorobenzyl)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one | 705249-21-4

• 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-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one
• 英文别名: 6-[(2,4-difluorophenyl)methyl]-8-methyl-2-(oxan-4-ylamino)pyrido[2,3-d]pyrimidin-7-one
• CAS: 705249-21-4
• 化学式: C₂₀H₂₀F₂N₄O₂
• 分子量: 386.401
• InChiKey: CXVKBXOZBZAXOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-(2,4-difluorobenzyl)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one 在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 0.5h， 以0.266 g的产率得到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 40.75h， 生成 6-(2,4-difluorobenzyl)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)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

• 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
• 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.