{4-[(4-溴-2-硝基苯基)氨基]-2-氯苯基}(2-甲基苯基)甲酮 | 321378-18-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: {4-[(4-溴-2-硝基苯基)氨基]-2-氯苯基}(2-甲基苯基)甲酮
• 英文名称: {4-[(4-bromo-2-nitrophenyl)amino]-2-chlorophenyl}(2-methylphenyl)methanone
• 英文别名: [4-(4-Bromo-2-nitroanilino)-2-chlorophenyl]-(2-methylphenyl)methanone
• CAS: 321378-18-1
• 化学式: C₂₀H₁₄BrClN₂O₃
• 分子量: 445.7
• InChiKey: IVDOSCGQIQWNFE-UHFFFAOYSA-N

物化性质

• 熔点：
  136-137 °C(Solv: ethanol (64-17-5))
• 沸点：
  525.9±50.0 °C(Predicted)
• 密度：
  1.537±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  27
• 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：

  {4-[(4-溴-2-硝基苯基)氨基]-2-氯苯基}(2-甲基苯基)甲酮 在 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以98%的产率得到{4-[(2-氨基-4-溴苯基)氨基]-2-氯苯基}(2-甲基苯基)甲酮
  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 {4-[(4-溴-2-硝基苯基)氨基]-2-氯苯基}(2-甲基苯基)甲酮
  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

• [EN] NOVEL AMINOBENZOPHENONES<br/>[FR] NOUVELLES AMINOBENZOPHENONES
  申请人：LEO PHARM PROD LTD

  公开号：WO2001005744A1

  公开（公告）日：2001-01-25

  The present invention relates to compounds of formula (I) wherein R1 represents one or more, similar or different substituents; R2 represents hydrogen, hydroxy, halogen, alkyl, alkoxy, alkylthio, or cyano; R3 represents one or more, similar or different substituents; and R6 represents hydrogen or methyl; and salts thereof with pharmaceutically acceptable acids, hydrates, and solvates, and to the use of compounds of general formula (II) in which formula R1 and R2 independently represent one or more, similar or different substituents; R3 represents hydrogen, halogen, hydroxy, mercapto, trifluoromethyl, amino, alkyl, alkoxy, alkylthio, alkylamino, or alkoxycarbonyl, phenyl, cyano, carboxy, or carbamoyl; R4, R5 and R6 represent independently hydrogen, trifluorormethyl, alkyl, carbamoyl, alkoxycarbonyl, or alkaloyl; X represents oxygen, N-OH, and N-O-alkyl, dialkoxy, cyclic dialkoxy, dialkylthio, or cyclic dialkylthio, and salts thereof with pharmaceutically acceptable, non-toxic acids. The compounds of the invention are useful in the human and veterinary practice.

  本发明涉及式（I）的化合物，其中R1代表一个或多个相似或不同的取代基；R2代表氢，羟基，卤素，烷基，烷氧基，烷硫基或氰基；R3代表一个或多个相似或不同的取代基；R6代表氢或甲基；以及与药学上可接受的酸盐，水合物和溶剂化物的盐，以及在通式（II）中使用通式R1和R2分别独立地代表一个或多个相似或不同的取代基；R3代表氢，卤素，羟基，巯基，三氟甲基，氨基，烷基，烷氧基，烷硫基，烷基氨基或烷氧羰基，苯基，氰基，羧基或氨基甲酰基；R4，R5和R6分别独立地代表氢，三氟甲基，烷基，氨基甲酰基，烷氧羰基或烷酰基；X代表氧，N-OH和N-O-烷基，二烷氧基，环二烷氧基，二烷基硫基或环二烷基硫基，以及与药学上可接受的无毒酸的盐。本发明的化合物在人类和兽医实践中有用。
• NOVEL AMINOBENZOPHENONES
  申请人：LEO PHARMACEUTICAL PRODUCTS LTD. A/S(LOVENS KEMISKE FABRIK PRODUKTIONSAKTIESELSKAB)

  公开号：EP1202954A1

  公开（公告）日：2002-05-08
• US6624199B1
  申请人：——

  公开号：US6624199B1

  公开（公告）日：2003-09-23
• Synthesis and Structure−Activity Relationship of Aminobenzophenones. A Novel Class of p38 MAP Kinase Inhibitors with High Antiinflammatory Activity
  作者：Erik Rytter Ottosen、Morten Dahl Sørensen、Fredrik Björkling、Tine Skak-Nielsen、Marianne Scheel Fjording、Helle Aaes、Lise Binderup

  DOI：10.1021/jm030851s

  日期：2003.12.1

  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).