[2-Chloro-4-(2-nitro-phenylamino)-phenyl]-o-tolyl-methanone | 210966-95-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [2-Chloro-4-(2-nitro-phenylamino)-phenyl]-o-tolyl-methanone
• 英文别名: [2-chloro-4-(2-nitroanilino)phenyl]-(2-methylphenyl)methanone
• CAS: 210966-95-3
• 化学式: C₂₀H₁₅ClN₂O₃
• 分子量: 366.804
• InChiKey: WOUBHHLWOZLESX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [2-Chloro-4-(2-nitro-phenylamino)-phenyl]-o-tolyl-methanone 在 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以89%的产率得到{2-chloro-4-[(2-aminophenyl)amino]phenyl}(2-methylphenyl)methanone
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Aminobenzophenones. A Novel Class of p38 MAP Kinase Inhibitors with High Antiinflammatory Activity

  摘要：

  We wish to report the synthesis and structure-activity relationship (SAR) of a series of 4-aminobenzophenones, as a novel compound class with high antiinflammatory activity. Our initial lead, {4-[(2-aminophenyl)amino]phenyl}(phenyl)methanone (3), was systematically optimized and resulted in compounds that potently inhibited the release of the proinflammatory cytokines IL-1beta and TNF-alpha in human peripheral blood mononuclear cells stimulated by LPS. One of the most potent compounds, among others, was {4-[(2-aminophenyl)amino]-2-chlorophenyl}(2-methylphenyl)methanone (45) with IC50 values of 14 and 6 nM for the inhibition of IL-1beta and TNF-alpha, respectively. Furthermore, we found these types of compounds to be potent and selective p38 MAP kinase inhibitors, e.g. 45 had an IC50 value of 10 nM. Molecular modeling was used to rationalize our SAR data and to propose a model for the interaction of compound 45 with the p38 MAP kinase. The model involved a favorable hydrogen bond between the carbonyl group of the benzophenone and the NH of Met-109, positioning ring A in the hydrophobic pocket I of the enzyme. Good antiinflammatory effects were demonstrated in two murine models of dermatitis after topical application (oxazolone and TPA model).

  DOI：

  10.1021/jm030851s
• 作为产物：
  描述：

  (2-氯-4-硝基苯基)(2-甲苯基)甲酮 在 potassium tert-butylate 、 tin(ll) chloride 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 22.0h， 生成 [2-Chloro-4-(2-nitro-phenylamino)-phenyl]-o-tolyl-methanone
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Aminobenzophenones. A Novel Class of p38 MAP Kinase Inhibitors with High Antiinflammatory Activity

  摘要：

  We wish to report the synthesis and structure-activity relationship (SAR) of a series of 4-aminobenzophenones, as a novel compound class with high antiinflammatory activity. Our initial lead, {4-[(2-aminophenyl)amino]phenyl}(phenyl)methanone (3), was systematically optimized and resulted in compounds that potently inhibited the release of the proinflammatory cytokines IL-1beta and TNF-alpha in human peripheral blood mononuclear cells stimulated by LPS. One of the most potent compounds, among others, was {4-[(2-aminophenyl)amino]-2-chlorophenyl}(2-methylphenyl)methanone (45) with IC50 values of 14 and 6 nM for the inhibition of IL-1beta and TNF-alpha, respectively. Furthermore, we found these types of compounds to be potent and selective p38 MAP kinase inhibitors, e.g. 45 had an IC50 value of 10 nM. Molecular modeling was used to rationalize our SAR data and to propose a model for the interaction of compound 45 with the p38 MAP kinase. The model involved a favorable hydrogen bond between the carbonyl group of the benzophenone and the NH of Met-109, positioning ring A in the hydrophobic pocket I of the enzyme. Good antiinflammatory effects were demonstrated in two murine models of dermatitis after topical application (oxazolone and TPA model).

  DOI：

  10.1021/jm030851s

文献信息

• AMINOBENZOPHENONES AS INHIBITORS OF INTERLEUKIN AND TNF
  申请人：LEO PHARMA A/S (with secondary name: LEO PHARMACEUTICAL PRODUCTS LTD. A/S)

  公开号：EP0966424B1

  公开（公告）日：2004-06-23
• US6313174B1
  申请人：——

  公开号：US6313174B1

  公开（公告）日：2001-11-06