(4-aminophenyl)(1,1'-biphenyl-2-yl)methanone | 210967-32-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (4-aminophenyl)(1,1'-biphenyl-2-yl)methanone
• 英文别名: (4-Aminophenyl)[1,1'-biphenyl]-2-ylmethanone；(4-aminophenyl)-(2-phenylphenyl)methanone
• CAS: 210967-32-1
• 化学式: C₁₉H₁₅NO
• 分子量: 273.334
• InChiKey: WKLKSQGGMLLLTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4-aminophenyl)(1,1'-biphenyl-2-yl)methanone 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-Amino-phenylamino)-phenyl]-biphenyl-2-yl-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-溴联苯 在 正丁基锂 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， 反应 6.33h， 生成 (4-aminophenyl)(1,1'-biphenyl-2-yl)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

• [EN] AMINOBENZOPHENONES AS INHIBITORS OF INTERLEUKIN AND TNF<br/>[FR] AMINOBENZOPHENONES EN TANT QU'INHIBITEURS D'INTERLEUKINE ET DE TNF
  申请人：LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LØVENS KEMISKE FABRIK PRODUKTIONSAKTIESELSKAB)

  公开号：WO1998032730A1

  公开（公告）日：1998-07-30

  (EN) The compounds of the present invention are represented by general formula (I) in which formula R1 and R2 stand independently for one or more, similar or different substituents selected from the group consisting of hydrogen, halogen, hydroxy, mercapto, trifluoromethyl, amino, alkyl, alkoxy, alkylthio, alkylamino, or alkoxycarbonyl, the C-content of which can be from 1 to 5, cyano, carboxy, carbamoyl, phenyl, or nitro; R3 stands for hydrogen, halogen, hydroxy, mercapto, trifluoromethyl, amino, alkyl, alkoxy, alkylthio, alkylamino, or alkoxycarbonyl, the C-content of which can be from 1 to 5, phenyl, cyano, carboxy, or carbamoyl; R4, R5 and R6 stand independently for hydrogen, trifluoromethyl, alkyl, carbamoyl, alkoxycarbonyl, or alkyloxo, the C-content of which can be from 1 to 5; X stands for oxygen, N-OH, N-O-alkyl, dialkoxy, cyclic dialkoxy, dialkylthio, or cyclic dialkylthio, the C-content of which can be from 1 to 5. The present compounds are of value in the human and veterinary practice as systemic and topical therapeutic agents for the treatment and prophylaxis of asthma, allergy, rheumatoid arthritis, spondyloarthritis, gout, atherosclerosis, chronic inflammatory bowel disease, proliferative and inflammatory skin disorders, such as psoriasis, and atopic dermatitis.(FR) Composés représentés par la formule suivante (I) dans laquelle R1 et R2 représentent indépendamment un ou plusieurs substituants semblables ou différents sélectionnés dans le groupe constitué par hydrogène, halogène, hydroxy, mercapto, trifluorométhyle, amino, alkyle, alkoxy, alkylthio, alkylamino ou alkoxycarbonyle, dont la teneur en C peut être de 1 à 5, cyano, carboxy, carbamoyle, phényle ou nitro; R3 représente hydrogène, halogène, hydroxy, mercapto, trifluorométhyle, amino, alkyle, alkoxy, alkylthio, alkylamino ou alkoxycarbonyle, dont la teneur en C peut être de 1 à 5, phényle, cyano, carboxy ou carbamoyle; R4, R5 et R6 représentent indépendamment hydrogène, trifluorométhyle, alkyle, carbamoyle, alkoxycarbonyle ou alkyloxo, dont la teneur en C peut être de 1 à 5; X représente oxygène, N-OH, N-O- alkyle, dialkoxy, dialkoxy cyclique, dialkylthio ou dialkylthio cyclique, dont la teneur en C peut être de 1 à 5. Ces composés sont utiles dans les domaines médicaux et vétérinaires en tant qu'agents thérapeutiques systémiques et topiques pour le traitement et la prophylaxie de l'asthme, de l'allergie, de la polyarthrite rhumatoïde, de la spondylarthrite, de la goutte, de l'athérosclérose, de la maladie chronique intestinale inflammatoire, de maladies de la peau prolifératives et inflammatoires, telles que le psoriasis et l'eczéma constitutionnel.

  本发明的化合物由一般式（I）表示，其中R1和R2分别代表氢、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等一种或多种相似或不同的取代基，其C含量可以为1至5，还可以是氰基、羧基、氨基甲酰基、苯基或硝基；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等一种或多种相似或不同的取代基，其C含量可以为1至5，还可以是苯基、氰基、羧基或氨基甲酰基；R4、R5和R6分别代表氢、三氟甲基、烷基、氨基甲酰基、烷氧羰基或烷氧基等一种或多种相似或不同的取代基，其C含量可以为1至5；X代表氧、N-OH、N-O-烷基、二烷氧基、环状二烷氧基、二烷基硫或环状二烷基硫等一种或多种相似或不同的取代基，其C含量可以为1至5。这些化合物在人类和兽医实践中作为系统和局部治疗剂，用于治疗和预防哮喘、过敏、类风湿性关节炎、脊柱关节炎、痛风、动脉硬化、慢性炎症性肠病、增生性和炎症性皮肤疾病，如银屑病和特应性皮炎等，具有重要的价值。
• AMINOBENZOPHENONES AS INHIBITORS OF INTERLEUKIN AND TNF
  申请人：LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS KEMISKE FABRIK PRODUKTIONSAKTIESELSKAB)

  公开号：EP0966424A1

  公开（公告）日：1999-12-29
• 7-ARYLSULFONAMIDO-2,3,4,5-TETRAHYDRO-1H-BENZO[D]AZEPINE DERIVATIVES WITH 5-HT6 RECEPTOR AFFINITY FOR THE TREATMENT OF CNS DISORDERS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1487801A1

  公开（公告）日：2004-12-22
• US6313174B1
  申请人：——

  公开号：US6313174B1

  公开（公告）日：2001-11-06
• [EN] 7-ARYLSULFONAMIDO-2,3,4,5-TETRAHYDRO-1H-BENZO'DIAZEPINE DERIVATIVES WITH 5-HT6 RECEPTOR AFFINITY FOR THE REATMENT OF CNS DISORDERS<br/>[FR] DERIVES DE 7-ARYLSULFONAMIDO-2,3,4,5-TETRAHYDRO-1H-BENZO'DIAZEPINE PRESENTANT UNE AFFINITE POUR LE RECEPTEUR 5-HT6, DESTINES AU TRAITEMENT DE TROUBLES DU SNC
  申请人：GLAXO GROUP LTD

  公开号：WO2003068751A1

  公开（公告）日：2003-08-21

  The present invention relates to novel sulfonamide compounds having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of CNS and other disorders.