{4-[(2-氨基-4-溴苯基)氨基]-2-氯苯基}(2-甲基苯基)甲酮 | 321351-00-2

• 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-[(2-氨基-4-溴苯基)氨基]-2-氯苯基}(2-甲基苯基)甲酮
• 英文名称: {4-[(2-amino-4-bromophenyl)amino]-2-chlorophenyl}(2-methylphenyl)methanone
• 英文别名: (4-((2-Amino-4-bromophenyl)amino)-2-chlorophenyl)-(2-methylphenyl)methanone；4-(2-amino-4-bromophenylamino)-2-chloro-2'-methylbenzophenone；EO 1428；(4-((2-Amino-4-bromophenyl)amino)-2-chlorophenyl)(2-methylphenyl)methanone；[4-(2-amino-4-bromoanilino)-2-chlorophenyl]-(2-methylphenyl)methanone
• CAS: 321351-00-2
• 化学式: C₂₀H₁₆BrClN₂O
• 分子量: 415.717
• InChiKey: HDCLCHNAEZNGNV-UHFFFAOYSA-N

物化性质

• 溶解度：
  在 DMSO 中溶解度为 100 mM，在乙醇中溶解度为 50 mM

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  25
• 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：
  55.1
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2922399090
• 储存条件：
  -20°C，密闭保存，干燥环境

制备方法与用途

EO 1428是一种氨基二苯甲酮类p38的高度特异性抑制剂。研究显示，EO 1428（1 μM）能显著减少脂多糖(LPS)诱导的肿瘤坏死因子α转化酶(TACE)活性上调。

反应信息

• 作为反应物：
  描述：

  氯甲酸氯甲酯 、 {4-[(2-氨基-4-溴苯基)氨基]-2-氯苯基}(2-甲基苯基)甲酮 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 1.5h， 生成 1-Chloromethyl N-[5-bromo-2-[3-chloro-4-(2-methylbenzoyl)-phenylamino]-phenyl]carbamate
  参考文献：
  名称：

  AMINOBENZOPHENONES AS INHIBITORS OF IL-1-BETA AND TNF-ALPHA

  摘要：

  公开号：

  EP1202959B1
• 作为产物：
  描述：

  (4-氨基-2-氯苯基)(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-[(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

文献信息

• Novel aminobenzoephenones
  申请人：——

  公开号：US20030119902A1

  公开（公告）日：2003-06-26

  The invention relates to a novel class of aminobenzophenones derivatives, to pharmaceutical preparations comprising said compounds, to dosage units of such preparations, to methods of treating patients comprising administering said compounds, and to the use of said compounds in the manufacture of pharmaceutical preparations.

  该发明涉及一种新型的氨基苯并酮衍生物类别，涉及包含该类化合物的药物制剂，涉及这种制剂的剂量单位，涉及包括给予该类化合物的治疗方法，以及涉及使用该类化合物制造药物制剂。
• [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 aminobenzophenone compounds
  申请人：Ottosen Rytter Erik

  公开号：US20060058380A1

  公开（公告）日：2006-03-16

  The invention provides novel compounds according to formula I relates to compounds with the general formula I said compounds being useful, e.g. in the treatment of inflammatory diseases.

  本发明提供了一种新的化合物，其符合公式I的化合物，所述化合物在治疗炎症性疾病等方面具有有用性。
• Aminobenzoephenones
  申请人：Leo Pharma A/S

  公开号：US07034015B2

  公开（公告）日：2006-04-25

  The invention relates to a novel class of aminobenzophenones derivatives, to pharmaceutical preparations comprising said compounds, to dosage units of such preparations, to methods of treating patients comprising administering said compounds, and to the use of said compounds in the manufacture of pharmaceutical preparations.

  本发明涉及一种新型的氨基苯并酮衍生物类，涉及包含该化合物的药物制剂、该制剂的剂量单位、包括给患者施用该化合物的治疗方法，以及在制造药物制剂时使用该化合物的用途。
• Dermal anti-inflammatory composition
  申请人：——

  公开号：US20020165286A1

  公开（公告）日：2002-11-07

  A pharmaceutical composition for dermal application comprises a lipophilic anti-inflammatory compound and a pharmaceutically acceptable vehicle comprising a lipophilic excipient capable of solubilizing the anti-inflammatory compound and targeting said compound to the pilosebaceous ducts on application of the composition on the skin. The composition may be used in the treatment of dermal inflammatory conditions, in particular acne.

  一种用于皮肤应用的制剂，包括一个亲脂性抗炎化合物和一种药学上可接受的载体，该载体包括一种亲脂性赋形剂，能够溶解抗炎化合物并将该化合物靶向应用于皮肤上的毛囊皮脂导管。该制剂可用于治疗皮肤炎症状况，特别是痤疮。