6-(2,4-difluorophenoxy)-2-isopropylamino-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one | 852022-92-5

• 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-isopropylamino-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one
• 英文别名: 6-(2,4-difluorophenoxy)-8-methyl-2-[(1-methylethyl)amino]pyrido[2,3-d]pyrimidin-7(8H)-one；6-(2,4-difluorophenoxy)-8-methyl-2-(propan-2-ylamino)pyrido[2,3-d]pyrimidin-7-one
• CAS: 852022-92-5
• 化学式: C₁₇H₁₆F₂N₄O₂
• 分子量: 346.336
• InChiKey: HAVJVJFXQRMACG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 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-difluorophenoxy)-2-isopropylamino-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 0.5h， 以0.317 g的产率得到6-(2,4-difluorophenoxy)-2-isopropylamino-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 43.25h， 生成 6-(2,4-difluorophenoxy)-2-isopropylamino-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

• Hydroxyalkyl substituted pyrido-7-pyrimidin-7-ones
  申请人：Goldstein Michael David

  公开号：US20080119497A1

  公开（公告）日：2008-05-22

  Compounds of the Formula: where X 1 , Ar 1 , R 1 , and R 2 are as defined herein, and compositions comprising the same. Also provided are methods for using compounds of Formula I in treating p38 mediated disorders in a patient.

  本发明提供了以下公式的化合物：其中X1，Ar1，R1和R2如定义所述，并且包括这些化合物的组合物。还提供了使用公式I的化合物治疗患者的p38介导的疾病的方法。
• US7348331B2
  申请人：——

  公开号：US7348331B2

  公开（公告）日：2008-03-25
• US7750016B2
  申请人：——

  公开号：US7750016B2

  公开（公告）日：2010-07-06
• 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.