N-(4-amino-2-benzoylphenyl)-2-phenylpropionic acid amide | 357436-75-0

• 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: N-(4-amino-2-benzoylphenyl)-2-phenylpropionic acid amide
• 英文别名: N-(4-amino-2-benzoylphenyl)-2-phenylpropionylamide；N-(4-amino-2-benzoylphenyl)-2-phenylpropanamide
• CAS: 357436-75-0
• 化学式: C₂₂H₂₀N₂O₂
• 分子量: 344.413
• InChiKey: ADVHJSVPUXDUQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  72.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-amino-2-benzoylphenyl)-2-phenylpropionic acid amide 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N-[[3-benzoyl-4-(2-phenylpropylamino)]phenyl]cysteinamide
  参考文献：
  名称：

  Synthesis, Molecular Modeling, and Structure−Activity Relationship of Benzophenone-Based CAAX-Peptidomimetic Farnesyltransferase Inhibitors

  摘要：

  Because of the involvement of farnesylated proteins in oncogenesis, inhibition of the protein-modifying enzyme farnesyltransferase is considered a major emerging strategy in cancer therapy. Here, we describe the structure-activity relationship of a novel class of CAAX-peptidomimetic farnesyltransferase inhibitors based on the benzophenone scaffold. 4 ' -Methyl, 4 ' -chloro, 4 ' -bromo, and 4 ' -nitrophenylacetic acid as substituents at the 2-amino group of the benzophenone core structure yield farnesyltransferase inhibitors active in the nanomolar range. Using diphenylacetic acid in this position further improves activity. SEAL superimposition of inhibitor 12a to the enzyme-bound conformation of a CAAX-peptide shows a markedly good resemblance of the molecular properties of the peptide. FlexX docking of 12a confirms the good fit of the molecule into the peptide binding site of farnesyltransferase. The novel benzophenone-based AAX-peptidomimetic substructure described here will be useful for the design of some novel types of farnesyltransferase inhibitors.

  DOI：

  10.1021/jm010872r
• 作为产物：
  描述：

  2-苯基丙酰氯 在 tin(ll) chloride 作用下， 以 乙酸乙酯 、 甲苯 为溶剂， 反应 6.0h， 生成 N-(4-amino-2-benzoylphenyl)-2-phenylpropionic acid amide
  参考文献：
  名称：

  Synthesis, Molecular Modeling, and Structure−Activity Relationship of Benzophenone-Based CAAX-Peptidomimetic Farnesyltransferase Inhibitors

  摘要：

  Because of the involvement of farnesylated proteins in oncogenesis, inhibition of the protein-modifying enzyme farnesyltransferase is considered a major emerging strategy in cancer therapy. Here, we describe the structure-activity relationship of a novel class of CAAX-peptidomimetic farnesyltransferase inhibitors based on the benzophenone scaffold. 4 ' -Methyl, 4 ' -chloro, 4 ' -bromo, and 4 ' -nitrophenylacetic acid as substituents at the 2-amino group of the benzophenone core structure yield farnesyltransferase inhibitors active in the nanomolar range. Using diphenylacetic acid in this position further improves activity. SEAL superimposition of inhibitor 12a to the enzyme-bound conformation of a CAAX-peptide shows a markedly good resemblance of the molecular properties of the peptide. FlexX docking of 12a confirms the good fit of the molecule into the peptide binding site of farnesyltransferase. The novel benzophenone-based AAX-peptidomimetic substructure described here will be useful for the design of some novel types of farnesyltransferase inhibitors.

  DOI：

  10.1021/jm010872r

文献信息

• Non-thiol farnesyltransferase inhibitors: n -(4-acylamino-3-benzoylphenyl)-3-[5-(4-nitrophenyl)-2-furyl]acrylic acid amides
  作者：Katja Kettler、Jacek Sakowski、Katrin Silber、Isabel Sattler、Gerhard Klebe、Martin Schlitzer

  DOI：10.1016/s0968-0896(03)00064-6

  日期：2003.4

  have designed the nitrophenylfurylacryl-substituted benzophenone 4f as a non-thiol farnesyltransferase inhibitor utilizing a novel aryl binding site of farnesyltransferase. Variation of the 2-acylamino substituent at the benzophenone core structure of our initial lead 4f yielded several non-thiol farnesyltransferase inhibitors with improved activity. These compounds display activity in the low nanomolar

  我们已经设计了硝基苯呋喃基丙烯酸取代的二苯甲酮4f作为非硫醇法呢基转移酶抑制剂，利用了法呢基转移酶的新型芳基结合位点。我们最初的铅4f的二苯甲酮核心结构处的2-酰基氨基取代基的变化产生了几种具有改进活性的非硫醇法呢基转移酶抑制剂。这些化合物在低纳摩尔范围内显示活性。
• Use of 2-phenylene diamine derivatives for the treatment of infections
  申请人：——

  公开号：US20030036532A1

  公开（公告）日：2003-02-20

  The invention relates to the use of compounds of formula (I), wherein n=0-3; R 1 , R 2 =H, alkyl, aryl, heteroaryl, acyl; R 3 =H, halogen, alkyl, aryl, heteroaryl, arylalkyl, acyl, CN, NO 2 , R 4 —X—; R 4 =H, alkyl, aryl, heteroaryl, aralkyl, acyl; X=NH, O, S, SO 2 , NHSO 2 , OSO 2 , and A, B, C=organic groups. The inventive compounds are used for the prophylaxis and the therapeutic treatment of infectious processes, especially of infectious processes caused by parasites. The invention further relates to medicaments that contain the inventive compounds.

  该发明涉及使用式(I)的化合物，其中n=0-3；R1、R2=H、烷基、芳基、杂环芳基、酰基；R3=H、卤素、烷基、芳基、杂环芳基、芳基烷基、酰基、CN、NO2、R4—X—；R4=H、烷基、芳基、杂环芳基、芳基烷基、酰基；X=NH、O、S、SO2、NHSO2、OSO2，以及A、B、C=有机基团。这些新颖化合物可用于预防和治疗感染过程，特别是由寄生虫引起的感染过程。该发明还涉及含有这些新颖化合物的药物。
• VERWENDUNG VON 2-PHENYLENDIAMINDERIVATEN ZUR BEHANDLUNG VON INFEKTIONEN
  申请人：Jomaa Pharmaka GmbH

  公开号：EP1257265A2

  公开（公告）日：2002-11-20
• [DE] VERWENDUNG VON 2-PHENYLENDIAMINDERIVATEN ZUR BEHANDLUNG VON INFEKTIONEN<br/>[EN] USE OF 2-PHENYLENE DIAMINE DERIVATIVES FOR THE TREATMENT OF INFECTIONS<br/>[FR] UTILISATION DE DERIVES DE 2-PHENYLENE DIAMINE POUR LE TRAITEMENT D'INFECTIONS
  申请人：JOMAA PHARMAKA GMBH

  公开号：WO2001062709A2

  公开（公告）日：2001-08-30

  Die Erfindung betrifft die Verwendung von Verbindungen der Formel (I), worin n = 0 - 3; R1, R2 = H, Alkyl, Aryl, Heteroaryl, Acyl; R3 = H, Halogen, Alkyl, Aryl, Heteroaryl, Arylalkyl, Acyl, CN, NO¿2?, R?4-X-; R4¿ = H, Alkyl, Aryl, Heteroaryl, Aralkyl, Acyl; X = NH, O, S, SO¿2?, NHSO2, OSO2, und A, B, C = organische Reste sind, zur prophylaktischen und therapeutischen Behandlung infektiöser Prozesse, insbesondere infektiöser, durch Parasiten hervorgerufener Prozesse, sowie Arzneimittel, die diese Verbindungen enthalten.
• Synthesis, Molecular Modeling, and Structure−Activity Relationship of Benzophenone-Based CAAX-Peptidomimetic Farnesyltransferase Inhibitors
  作者：Jacek Sakowski、Markus Böhm、Isabel Sattler、Hans-Martin Dahse、Martin Schlitzer

  DOI：10.1021/jm010872r

  日期：2001.8.1

  Because of the involvement of farnesylated proteins in oncogenesis, inhibition of the protein-modifying enzyme farnesyltransferase is considered a major emerging strategy in cancer therapy. Here, we describe the structure-activity relationship of a novel class of CAAX-peptidomimetic farnesyltransferase inhibitors based on the benzophenone scaffold. 4 ' -Methyl, 4 ' -chloro, 4 ' -bromo, and 4 ' -nitrophenylacetic acid as substituents at the 2-amino group of the benzophenone core structure yield farnesyltransferase inhibitors active in the nanomolar range. Using diphenylacetic acid in this position further improves activity. SEAL superimposition of inhibitor 12a to the enzyme-bound conformation of a CAAX-peptide shows a markedly good resemblance of the molecular properties of the peptide. FlexX docking of 12a confirms the good fit of the molecule into the peptide binding site of farnesyltransferase. The novel benzophenone-based AAX-peptidomimetic substructure described here will be useful for the design of some novel types of farnesyltransferase inhibitors.