N-(4-amino-2-benzoylphenyl)-1-naphthoyl amide | 366456-39-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(4-amino-2-benzoylphenyl)-1-naphthoyl amide
• 英文别名: N-(4-amino-2-benzoylphenyl)naphthalene-1-carboxamide
• CAS: 366456-39-5
• 化学式: C₂₄H₁₈N₂O₂
• 分子量: 366.419
• InChiKey: SBNKSSRWETXXER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 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)-1-naphthoyl 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-(1-naphthoylamino)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：

  1-萘甲酰氯 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)-1-naphthoyl 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: structure–activity relationships of benzophenone-based bisubstrate analogue farnesyltransferase inhibitors
  作者：Martin Schlitzer、Markus Böhm、Isabel Sattler

  DOI：10.1016/s0968-0896(01)00312-1

  日期：2002.3

  structure-activity relationships of benzophenone-based bisubstrate analogue farnesyltransferase inhibitors yielded a bisubstrate analogue farnesyltransferase inhibitor lacking any prenylic or peptidic substructures with nanomolar activity. This represents a considerable progress in comparison to those non-prenylic, non-peptidic bisubstrate analogue farnesyltransferase inhibitors we have described before which

  对基于二苯甲酮的双底物类似物法尼基转移酶抑制剂的结构-活性关系的研究产生了一种双底物类似物法尼基转移酶抑制剂，该抑制剂缺乏任何具有纳摩尔活性的前烯基或肽亚结构。与我们之前所述的那些非烯丙基，非肽双底物类似物法尼基转移酶抑制剂相比，这代表了可观的进步，因为它们利用的AAX拟肽亚结构不同于二苯甲酮，因为这些抑制剂仅在微摩尔范围内显示活性。
• Non-thiol Farnesyltransferase Inhibitors: N-(4-Acylamino-3-benzoylphenyl)-4-nitrocinnamic Acid Amides
  作者：Jacek Sakowski、Isabel Sattler、Martin Schlitzer

  DOI：10.1016/s0968-0896(01)00274-7

  日期：2002.2

  novel non-thiol farnesyltransferase inhibitor. Replacement of the p-tolyl moiety of our initial lead structure 4a by different para and ortho substituted phenyl residues as well as by 1-naphthyl resulted in derivatives with considerably enhanced activity displaying IC(50) values between 42 and 52 nM. These compounds represent novel, readily accessible non-thiol farnesyltransferase inhibitors being

  我们已经开发了4-硝基肉桂酰基取代的二苯甲酮4a作为新型的非硫醇法呢基转移酶抑制剂。用不同的对位和邻位取代的苯基残基以及1-萘基取代我们最初的铅结构4a的对甲苯基部分，得到的衍生物具有显着增强的活性，显示的IC（50）值为42至52 nM。这些化合物代表了新颖的，易于获得的非硫醇法尼基转移酶抑制剂，其活性高于相应的含硫醇类似物。
• 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。
• Structure–Activity Relationships of Novel Anti-Malarial Agents. Part 3: N-(4-Acylamino-3-benzoylphenyl)-4-propoxycinnamic Acid Amides
  作者：Jochen Wiesner、Katja Kettler、Hassan Jomaa、Martin Schlitzer

  DOI：10.1016/s0960-894x(01)00798-3

  日期：2002.2

  We have described 5-(4-propoxycinnamoylamino)-2-(4-tolylacetylamino)benzophenone 6e as a novel lead for antimalarial agents. Anti-malarial activity of these 5-(4-propoxycinnamoylamino)benzophenones proved to be quite sensitive against variations of the acyl substituent at the 2-amino group. Best activity was obtained with phenylacetic acid moieties carrying small substituents in the para-position. From the para-substituents evaluated, the trifluoromethyl group yielded the most active compound (6j) in this series (IC50 = 120 nM). Deviations from the phenylacetic acid substructure, shifting the substituent into the ortho-position or bulkier para-substituents resulted in a significant reduction in anti-malarial activity. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Structure–Activity relationships of novel anti-Malarial agents: Part 5. N-(4-acylamino-3-benzoylphenyl)-[5-(4-nitrophenyl)-2-furyl]acrylic acid amides
  作者：Jochen Wiesner、Katja Kettler、Jacek Sakowski、Regina Ortmann、Hassan Jomaa、Martin Schlitzer

  DOI：10.1016/s0960-894x(02)01003-x

  日期：2003.2

  We have developed the [5-(4-nitrophenyl)-2-furyl]acrylic acid substituted benzophenone 4g as a novel lead for antimalarial agents. Here, we demonstrated that the acyl residue at the 2-amino group of the benzophenone core structure has to be a phenylacetic acid substructure substituted in its para-position with methyl or other substituents of similar size. The triauoromethyl substituted derivative displayed an IC50 of 47 nM against the multi-drug resistant Plasmodium falciparum strain Dd2. (C) 2002 Elsevier Science Ltd. All rights reserved.