{2-chloro-4-[(2-aminophenyl)amino]phenyl}(2-methylphenyl)methanone | 210966-22-6

• 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-aminophenyl)amino]phenyl}(2-methylphenyl)methanone
• 英文别名: 4-(2-aminophenylamino)-2-chloro-2'-methylbenzophenone；[4-(2-aminoanilino)-2-chlorophenyl]-(2-methylphenyl)methanone
• CAS: 210966-22-6
• 化学式: C₂₀H₁₇ClN₂O
• 分子量: 336.821
• InChiKey: MSXZXFPYTVQJIL-UHFFFAOYSA-N

物化性质

• 熔点：
  113-114 °C
• 沸点：
  486.3±45.0 °C(Predicted)
• 密度：
  1.275±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  24
• 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

反应信息

• 作为反应物：
  描述：

  {2-chloro-4-[(2-aminophenyl)amino]phenyl}(2-methylphenyl)methanone 在 苯磺酰氯 作用下， 以 吡啶 为溶剂， 生成 N-(2-{[3-Chloro-4-(2-methylbenzoyl)phenyl]amino}phenyl)-benzenesulfonamide
  参考文献：
  名称：

  Novel aminobenzoephenones

  摘要：

  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。

  公开号：

  US20030119902A1
• 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 26.0h， 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

文献信息

• Novel aminophenyl ketone derivatives
  申请人：——

  公开号：US20030073832A1

  公开（公告）日：2003-04-17

  Novel heteroaryl aminophenyl ketone derivatives which are inhibitors of MAP kinases, in particular the p38 MAP kinase, are useful as anti-inflammatory agents in the prophylaxis or treatment of inflammatory diseases or conditions.

  新颖的杂环烷基氨基苯酮衍生物是MAP激酶的抑制剂，特别是p38 MAP激酶，在预防或治疗炎症性疾病或症状中作为抗炎药物是有用的。
• [EN] NOVEL AMINOBENZOPHENONE COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES D'AMINOBENZOPHENONE
  申请人：LEO PHARMA AS

  公开号：WO2005009940A1

  公开（公告）日：2005-02-03

  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, ophthalmic diseases or cancer.

  该发明提供了根据式I的新化合物，与一般式I相关的化合物，这些化合物在治疗炎症、眼科疾病或癌症等方面具有用途。
• Triazole substituted aminobenzophenone compounds
  申请人：Erik Rytter Ottosen

  公开号：US20060128766A1

  公开（公告）日：2006-06-15

  The invention relates to novel compounds according to formula Ia and Ib, said compounds being useful, e.g. in the treatment of inflammatory, ophthalmic diseases, or cancer.

  该发明涉及根据式Ia和Ib的新化合物，这些化合物可用于治疗炎症性、眼科疾病或癌症等疾病。
• Aminobenzophenones as inhibitors of interleukin and TNF
  申请人：Leo Pharmaceutical Products Ltd.A/S/ (Løvens kemiske Fabrik Produktionsaktieselskab)

  公开号：US06313174B1

  公开（公告）日：2001-11-06

  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.

  本发明的化合物由一般式（I）表示，其中式中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，其碳含量可为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，其碳含量可为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，其碳含量可为1至5；X代表氧、N—OH、N—O-烷基、二烷氧基、环二烷氧基、二烷硫基或环二烷硫基等，其碳含量可为1至5。这些化合物在人类和兽医实践中具有重要价值，可作为系统和局部治疗剂，用于哮喘、过敏、类风湿关节炎、脊柱关节炎、痛风、动脉粥样硬化、慢性炎性肠病、增生性和炎症性皮肤疾病（如银屑病）以及特应性皮炎的治疗和预防。
• Aminobenzophenones as inhibitors of IL-1&bgr; and TNF-&agr;
  申请人：Leo Pharmaceutical Products Ltd. a/s (Lovens Kemiske Fabrik Produktionsaktieselskab)

  公开号：US06566554B1

  公开（公告）日：2003-05-20

  The present invention relates to a compound of general formula (I) wherein R1, R2, and R3 represents one or more, same or different substituents selected from the group consisting of halogen, hydroxy, mercapto, trifluoromethyl, amino, (C1-C3)alkyl, (C2-C3)olefinic group, (C1-C3)alkoxy, (C1-C3)akylthio, (C1-C6)alkylamino, (C1-C3)alkoxycarbonyl, cyano, —CONH2, phenyl, or nitro; further R2 can be hydrogen, and R3 can be carboxy and carbamoyl; R4 represents hydrogen, (C1-C3)alkyl, or allyl; X represents oxygen or sulphur; Q represents —(CO)—, —(CS)—, or a bond; Y represents (C5-C15)alkyl; (C2-C15)olefinic group; (C3-C10)monocyclic hydrocarbon group; or phenyl; any of which may be optionally substituted by one or more, same or different substituents selected from the group consisting of the formula R5 defined below; (C1-C4)alkyl substituted by one or more substituents selected for the group R5; or a group of the formula —(Z—O)n—Z, wherein Z is a (C1-C3)alkyl, n is an integer >1; and no continuous linear sequence of atoms in the group Y exceeds 15; R5 represents halogen, hydroxy, mercapto, trifluoromethyl, amino, (C1-C3)alkoxy, (C1-C3)alkylthio, (C1-C6)alkylamino, (C1-C3)alkoxycarbonyl, cyano, azido, nitro, —COOH, —CONH2, —CONHR′, or COONR′R′ wherein R′ represents (C1-C3)alkyl; or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof. The compounds are valuable in the human and veterinary therapy.

  本发明涉及一般式（I）的化合物，其中R1、R2和R3代表自卤素、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、苯基或硝基等基团中选择的一个或多个相同或不同的取代基；此外，R2可以是氢，R3可以是羧基和氨基甲酰基；R4代表氢、（C1-C3）烷基或烯丙基；X代表氧或硫；Q代表—（CO）—、—（CS）—或键；Y代表（C5-C15）烷基、（C2-C15）烯基、（C3-C10）单环碳氢基团或苯基；其中任何一个可以选择地由下面定义的R5基团中的一个或多个相同或不同的取代基取代；（C1-C4）烷基由R5基团中选择的一个或多个取代基取代；或者一个式子—（Z—O）n—Z，其中Z是（C1-C3）烷基，n是大于1的整数；Y中的原子没有连续的线性序列超过15个；R5代表卤素、羟基、巯基、三氟甲基、氨基、（C1-C3）烷氧基、（C1-C3）烷硫基、（C1-C6）烷基氨基、（C1-C3）烷氧羰基、氰基、偶氮基、硝基、—COOH、—CONH2、—CONHR′或COONR′R′，其中R′代表（C1-C3）烷基；或其药学上可接受的盐，或其水合物或溶剂合物。这些化合物在人类和兽医治疗中具有价值。