R-2-(2,4-difluorophenylamino)-8-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-10,11-dihydro-dibenzo[a,d]cyclohepten-5-one | 1383443-36-4

• 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: R-2-(2,4-difluorophenylamino)-8-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-10,11-dihydro-dibenzo[a,d]cyclohepten-5-one
• 英文别名: 6-(2,4-difluoroanilino)-13-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]tricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-one
• CAS: 1383443-36-4
• 化学式: C₂₇H₂₅F₂NO₄
• 分子量: 465.497
• InChiKey: BSJHGNQUVPKGIL-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  R-2-(2,4-difluorophenylamino)-8-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-10,11-dihydro-dibenzo[a,d]cyclohepten-5-one 在 对甲苯磺酸 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 以87.5%的产率得到S-2-(2,4-difluorophenylamino)-8-(2,3-dihydroxypropoxy)-10,11-dihydro-dibenzo-[a,d]cyclohepten-5-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Disubstituted Dibenzosuberones as Highly Potent and Selective Inhibitors of p38 Mitogen Activated Protein Kinase

  摘要：

  Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical properties as well as potency. Extremely potent inhibitors were obtained, with half-maximal inhibitory concentration (IC50) values in the low nM range in a whole blood assay measuring the inhibition of cytokine release. The high potency of the target compounds together with the outstanding selectivity of this novel class of compounds toward p38 mitogen activated protein (MAP) kinase compared to other kinases indicate them to be most applicable as tools in pharmacological research and eventually they may foster a new generation of anti-inflammatory drugs.

  DOI：

  10.1021/jm300327h
• 作为产物：
  描述：

  4-甲氧基-2-甲基苯甲酸 在 N-溴代丁二酰亚胺(NBS) 、 氯化亚砜 、 偶氮二异丁腈 、 palladium on activated charcoal 、 氢溴酸 、 氢气 、 palladium diacetate 、 potassium carbonate 、 溶剂黄146 、 三苯基膦 、 sodium t-butanolate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 氯苯 、 丙酮 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， 反应 47.0h， 生成 R-2-(2,4-difluorophenylamino)-8-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-10,11-dihydro-dibenzo[a,d]cyclohepten-5-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Disubstituted Dibenzosuberones as Highly Potent and Selective Inhibitors of p38 Mitogen Activated Protein Kinase

  摘要：

  Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical properties as well as potency. Extremely potent inhibitors were obtained, with half-maximal inhibitory concentration (IC50) values in the low nM range in a whole blood assay measuring the inhibition of cytokine release. The high potency of the target compounds together with the outstanding selectivity of this novel class of compounds toward p38 mitogen activated protein (MAP) kinase compared to other kinases indicate them to be most applicable as tools in pharmacological research and eventually they may foster a new generation of anti-inflammatory drugs.

  DOI：

  10.1021/jm300327h