3-Chloro-1-(2,6-difluorophenyl)-4-[(2,4-difluorophenyl)methoxy]-6-[(dimethylamino)methyl]pyridin-2-one | 586386-51-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-Chloro-1-(2,6-difluorophenyl)-4-[(2,4-difluorophenyl)methoxy]-6-[(dimethylamino)methyl]pyridin-2-one
• CAS: 586386-51-8
• 化学式: C₂₁H₁₇ClF₄N₂O₂
• 分子量: 440.825
• InChiKey: IBAUPDOUTIJFLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	3-chloro-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-6-(hydroxymethyl)pyridine-2(1H)-one	586379-29-5	C19H12ClF4NO3	413.756
  ——	1-(2,6-Difluorophenyl)-4-[(2,4-difluorophenyl)methoxy]-6-methylpyridin-2-one	586387-35-1	C19H13F4NO2	363.311
  ——	4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-6-(hydroxymethyl)pyridin-2(1H)-one	586379-27-3	C19H13F4NO3	379.311
  ——	4-[(2,4-Difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-6-oxo-1,6-dihydropyridine-2-carbaldehyde	586379-26-2	C19H11F4NO3	377.295

反应信息

• 作为产物：
  描述：

  1-(2,6-Difluorophenyl)-4-[(2,4-difluorophenyl)methoxy]-6-methylpyridin-2-one 在 selenium(IV) oxide 、 sodium tetrahydroborate 、 N-氯代丁二酰亚胺 、 三乙酰氧基硼氢化钠 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 溶剂黄146 、 乙腈 为溶剂， 反应 13.5h， 生成 3-Chloro-1-(2,6-difluorophenyl)-4-[(2,4-difluorophenyl)methoxy]-6-[(dimethylamino)methyl]pyridin-2-one
  参考文献：
  名称：

  Design, synthesis and activity of a potent, selective series of N -aryl pyridinone inhibitors of p38 kinase

  摘要：

  A series of N-aryl pyridinone inhibitors of p38 mitogen activated protein (MAP) kinase were designed and prepared based on the screening hit SC-25028 (1) and structural comparisons to VX-745 (5). The focus of the investigation targeted the dependence of potency and metabolic stability on the benzyloxy connectivity, the role of the C-6 position and the substitution pattern on the N-phenyl ring. Further optimization produced the highly selective and potent pyridinones 2 and 3. These inhibitors exhibited activity in both acute and chronic models of inflammation. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.120

文献信息

• Substituted pyridinones
  申请人：Devadas Balekudru

  公开号：US20050176775A1

  公开（公告）日：2005-08-11

  Disclosed are compounds of Formula I and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 , and R 5 are defined herein. These compounds are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP Kinase and/or TNF activity. Pharmaceutical compositions containing the compounds, methods of preparing the compounds and methods of treatment using the compounds are also disclosed.

  本发明涉及式I的化合物及其药学上可接受的盐，其中R1、R2、R3、R4和R5在此被定义。这些化合物可用于治疗由未调节的p38 MAP激酶和/或TNF活性引起或加剧的疾病和状况。本发明还涉及含有这些化合物的药物组合物、制备这些化合物的方法以及使用这些化合物的治疗方法。
• SUBSTITUTED PYRIDINONES AS MODULATORS OF P38 MAP KINASE
  申请人：Pharmacia Corporation

  公开号：EP1490064B1

  公开（公告）日：2009-11-18
• US7067540B2
  申请人：——

  公开号：US7067540B2

  公开（公告）日：2006-06-27
• US7629363B2
  申请人：——

  公开号：US7629363B2

  公开（公告）日：2009-12-08
• [EN] SUBSTITUTED PYRIDINONES<br/>[FR] PYRIDINONES SUBSTITUES
  申请人：PHARMACIA CORP

  公开号：WO2005018557A2

  公开（公告）日：2005-03-03

  Disclosed are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, and R5 are defined herein. These compounds are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP Kinase and/or TNF activity. Pharmaceutical compositions containing the compounds, methods of preparing the compounds and methods of treatment using the compounds are also disclosed.