(4-氨基-2-氯苯基)(2-甲苯基)甲酮 | 210967-34-3

• 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-氨基-2-氯苯基)(2-甲苯基)甲酮
• 英文名称: (4-amino-2-chlorophenyl)(2-methylphenyl)methanone
• 英文别名: (4-amino-2-chlorophenyl)-(2-methylphenyl)methanone
• CAS: 210967-34-3
• 化学式: C₁₄H₁₂ClNO
• 分子量: 245.708
• InChiKey: KWMMPYUINBQSLM-UHFFFAOYSA-N

物化性质

• 熔点：
  94-96 °C
• 沸点：
  396.3±32.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 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-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 {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-硝基苯甲酰氯 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-氨基-2-氯苯基)(2-甲苯基)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。
• Aminobenzophenones as inhibitors of il 1b and tnf
  申请人：——

  公开号：US20030013770A1

  公开（公告）日：2003-01-16

  A compound of the general formula I 1 wherein R 1 represents a substituent selected from the group consisting of halogen, hydroxy, mercapto, trifluoromethyl, amino, (C 1 -C 3 )alkyl, (C 2 -C 3 )olefinic group, (C 1 -C 3 )alkoxy, (C 1 -C 3 )alkylthio, (C 1 -C 6 )alkylamino, (C 1 -C 3 )alkoxycarbonyl, cyano, —CONH 2 , phenyl, and nitro; R 2 represents one or more, same or different substituents selected from the group consisting of hydrogen, halogen, hydroxy, mercapto, trifluoromethyl, amino, (C 1 -C 3 )alkyl, (C 2 -C 3 )olefinic group, (C 1 -C 3 )alkoxy, (C 1 -C 3 )alkylthio, (C 1 -C 6 )alkylamino, (C 1 -C 3 )alkoxycarbonyl, cyano, —CONH 2 , phenyl, and nitro; R 3 represents one or more, same or different substituents selected from the group consisting of hydrogen, halogen, hydroxy, mercapto, trifluoromethyl, cyano, carboxy, carbamoyl, (C 1 -C 10 )alkyl, (C 2 -C 10 )olefinic group, (C 3 -C 8 )monocyclic hydrocarbon group, (C 1 -C 10 )alkoxy, (C 1 -C 10 )alkylthio, (C 1 -C 10 )alkoxycarbonyl, and phenyl; R 4 represents hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )olefinic group, or (C 3 -C 6 )monocyclic hydrocarbon group; R 5 represents one or more, same or different substituents selected from the group consisting of hydrogen and R 1 ; X represents oxygen, sulphur, or N—OH; and salts thereof with pharmaceutically acceptable acids, hydrates and solvates, may be used in the prophylaxis or treatment of inflammatory diseases.

  一种通式为I1的化合物，其中R1代表从卤素、羟基、巯基、三氟甲基、氨基、(C1-C3)烷基、(C2-C3)烯基、(C1-C3)烷氧基、(C1-C3)烷硫基、(C1-C6)烷基氨基、(C1-C3)烷氧羰基、氰基、-CONH2、苯基和硝基中选择的取代基；R2代表从氢、卤素、羟基、巯基、三氟甲基、氨基、(C1-C3)烷基、(C2-C3)烯基、(C1-C3)烷氧基、(C1-C3)烷硫基、(C1-C6)烷基氨基、(C1-C3)烷氧羰基、氰基、-CONH2、苯基和硝基中选择的一个或多个相同或不同的取代基；R3代表从氢、卤素、羟基、巯基、三氟甲基、氰基、羧基、氨基、(C1-C10)烷基、(C2-C10)烯基、(C3-C8)单环碳氢基团、(C1-C10)烷氧基、(C1-C10)烷硫基、(C1-C10)烷氧羰基和苯基中选择的一个或多个相同或不同的取代基；R4代表氢、(C1-C6)烷基、(C2-C6)烯基或(C3-C6)单环碳氢基团；R5代表从氢和R1中选择的一个或多个相同或不同的取代基；X代表氧、硫或N-OH；以及其与药学上可接受的酸盐、水合物和溶剂化合物，可用于预防或治疗炎症性疾病。
• Benzophenones as inhibitors of IL-1beta and TNF-alpha
  申请人：——

  公开号：US20020016347A1

  公开（公告）日：2002-02-07

  Heteroaryl aminobenzophenones of general formula I inhibit interleukin-1&bgr; and TNF-&agr; and may therefore be useful in the therapy of inflammatory diseases and conditions.

  通式为I的杂环氨基苯酮抑制白细胞介素-1β和TNF-α，因此可能在治疗炎症性疾病和状况中有用。
• [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。
• 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。