13-(2,4-difluoroanilino)-N-(2-methylsulfanylethyl)-2-oxotricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene-5-carboxamide | 1417404-34-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: 13-(2,4-difluoroanilino)-N-(2-methylsulfanylethyl)-2-oxotricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene-5-carboxamide
• CAS: 1417404-34-2
• 化学式: C₂₅H₂₂F₂N₂O₂S
• 分子量: 452.525
• InChiKey: DIRVUWQATBAJMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  83.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Oxone 、 13-(2,4-difluoroanilino)-N-(2-methylsulfanylethyl)-2-oxotricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene-5-carboxamide 以 四氢呋喃 、 水 为溶剂， 以64%的产率得到13-(2,4-difluoroanilino)-N-(2-methylsulfonylethyl)-2-oxotricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene-5-carboxamide
  参考文献：
  名称：

  Dibenzosuberones as p38 Mitogen-Activated Protein Kinase Inhibitors with Low ATP Competitiveness and Outstanding Whole Blood Activity

  摘要：

  p38 alpha mitogen-activated protein (MAP) kinase is a main target in drug research concerning inflammatory diseases. Nevertheless, no inhibitor of p38 alpha MAP kinase has been introduced to the market. This might be attributed to the fact that there is no inhibitor which combines outstanding activity in biological systems and selectivity. Herein an approach to the development of such inhibitors on the basis of the highly selective molecular probe Skepinone-L is described. Introduction of a "deep pocket" moiety addressing the DFG motif led to an increased activity of the compounds. Hydrophilic moieties, addressing the solvent-exposed area adjacent to hydrophilic region II, conserved a high activity of the compounds in a whole blood assay. Combined with their outstanding selectivity and low ATP competitiveness, these inhibitors are very interesting candidates for use in biological systems and in therapy.

  DOI：

  10.1021/jm301539x
• 作为产物：
  描述：

  4-甲基-异酞腈 在 盐酸 、 aluminum (III) chloride 、 正丁基锂 、 氯化亚砜 、 硫酸 、 potassium tert-butylate 、 水 、 palladium diacetate 、 二异丙胺 、 potassium hydroxide 、 sodium hydroxide 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 甲苯 、 叔丁醇 、 二乙二醇 为溶剂， 反应 143.83h， 生成 13-(2,4-difluoroanilino)-N-(2-methylsulfanylethyl)-2-oxotricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene-5-carboxamide
  参考文献：
  名称：

  Dibenzosuberones as p38 Mitogen-Activated Protein Kinase Inhibitors with Low ATP Competitiveness and Outstanding Whole Blood Activity

  摘要：

  p38 alpha mitogen-activated protein (MAP) kinase is a main target in drug research concerning inflammatory diseases. Nevertheless, no inhibitor of p38 alpha MAP kinase has been introduced to the market. This might be attributed to the fact that there is no inhibitor which combines outstanding activity in biological systems and selectivity. Herein an approach to the development of such inhibitors on the basis of the highly selective molecular probe Skepinone-L is described. Introduction of a "deep pocket" moiety addressing the DFG motif led to an increased activity of the compounds. Hydrophilic moieties, addressing the solvent-exposed area adjacent to hydrophilic region II, conserved a high activity of the compounds in a whole blood assay. Combined with their outstanding selectivity and low ATP competitiveness, these inhibitors are very interesting candidates for use in biological systems and in therapy.

  DOI：

  10.1021/jm301539x

文献信息

• Dibenzosuberones as p38 Mitogen-Activated Protein Kinase Inhibitors with Low ATP Competitiveness and Outstanding Whole Blood Activity
  作者：Stefan Fischer、Heike K. Wentsch、Svenja C. Mayer-Wrangowski、Markus Zimmermann、Silke M. Bauer、Kirsten Storch、Raimund Niess、Solveigh C. Koeberle、Christian Grütter、Frank M. Boeckler、Daniel Rauh、Stefan A. Laufer

  DOI：10.1021/jm301539x

  日期：2013.1.10

  p38 alpha mitogen-activated protein (MAP) kinase is a main target in drug research concerning inflammatory diseases. Nevertheless, no inhibitor of p38 alpha MAP kinase has been introduced to the market. This might be attributed to the fact that there is no inhibitor which combines outstanding activity in biological systems and selectivity. Herein an approach to the development of such inhibitors on the basis of the highly selective molecular probe Skepinone-L is described. Introduction of a "deep pocket" moiety addressing the DFG motif led to an increased activity of the compounds. Hydrophilic moieties, addressing the solvent-exposed area adjacent to hydrophilic region II, conserved a high activity of the compounds in a whole blood assay. Combined with their outstanding selectivity and low ATP competitiveness, these inhibitors are very interesting candidates for use in biological systems and in therapy.