5-amino-2-(p-tolylacetylamino)benzophenone | 265648-28-0

• 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: 5-amino-2-(p-tolylacetylamino)benzophenone
• 英文别名: N-(4-amino-2-benzoylphenyl)-(4-methylphenyl)acetamide；N-(4-amino-2-benzoylphenyl)-4-tolylacetic acid amide；Acetamide, N-(4-amino-2-benzoylphenyl)-2-p-tolyl-；N-(4-amino-2-benzoylphenyl)-2-(4-methylphenyl)acetamide
• CAS: 265648-28-0
• 化学式: C₂₂H₂₀N₂O₂
• 分子量: 344.413
• InChiKey: NPFWHOVDUNKUOX-UHFFFAOYSA-N

物化性质

• 熔点：
  159 °C
• 沸点：
  563.2±50.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 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：

  5-amino-2-(p-tolylacetylamino)benzophenone 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-(4-methylphenyl)acetylamino]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：

  对甲苯乙酰氯 在 tin(ll) chloride 作用下， 以 乙酸乙酯 、 甲苯 为溶剂， 反应 6.0h， 生成 5-amino-2-(p-tolylacetylamino)benzophenone
  参考文献：
  名称：

  非硫醇法呢基转移酶抑制剂：基于二苯甲酮的双底物类似物法呢基转移酶抑制剂的概念。

  摘要：

  基于二苯甲酮的CAAX-拟肽法呢基转移酶抑制剂中的巯基被羧酸部分取代，导致抑制力显着下降。通过添加亲脂性烷基链将这些羧酸衍生物转化为双底物类似物，该亲脂性烷基链应能够占据法呢基转移酶活性位点的法呢基结合区域的相当大的部分，从而恢复了抑制活性。这些双底物类似物代表了非硫醇法呢基转移酶抑制剂的新的先导结构。

  DOI：

  10.1016/s0223-5234(00)00162-8

文献信息

• Non-thiol Farnesyltransferase Inhibitors: Utilization of the Far Aryl Binding Site by 5-Cinnamoylaminobenzophenones
  作者：Andreas Mitsch、Pia Wißner、Markus Böhm、Katrin Silber、Gerhard Klebe、Isabel Sattler、Martin Schlitzer

  DOI：10.1002/ardp.200400871

  日期：2004.9

  We recently described two novel aryl binding sites of farnesyltransferase. In this study, the cinnamoyl residue was designed as an appropriate substituent for our benzophenone‐based AAX‐peptidomimetic compound capable of occupying the far aryl binding site.

  我们最近描述了法呢基转移酶的两个新的芳基结合位点。在这项研究中，肉桂酰基残基被设计为我们基于二苯甲酮的 AAX 肽模拟化合物的合适取代基，能够占据远芳基结合位点。
• Non-Thiol farnesyltransferase inhibitors: utilization of an aryl binding site by 5-arylacryloylaminobenzophenones
  作者：Andreas Mitsch、Markus Böhm、Pia Wißner、Isabel Sattler、Martin Schlitzer

  DOI：10.1016/s0968-0896(02)00088-3

  日期：2002.8

  We recently described a novel aryl binding site of farnesyltransferase. The 2-naphthylacryloyl residue was developed as an appropriate substituent for our benzophenone-based AAX-peptidomimetic capable of occupying this binding site, resulting in a non-thiol farnesyltransferase inhibitor with nanomolar activity. The activity of this inhibitor is readily explained on the basis of docking studies which

  我们最近描述了法呢基转移酶的新型芳基结合位点。开发2-萘基丙烯酰基残基作为我们基于二苯甲酮的AAX-拟肽能够占据该结合位点的合适取代基，从而产生具有纳摩尔活性的非硫醇法呢基转移酶抑制剂。根据对接研究容易地解释了该抑制剂的活性，对接研究表明2-萘基残基适合于芳基结合位点。
• 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: Structure-Activity Relationships of Aralkylsubsituted Benzophenones
  作者：Andreas Mitsch、Pia Wißner、Isabel Sattler、Martin Schlitzer

  DOI：10.1002/1521-4184(200102)334:2<40::aid-ardp40>3.0.co;2-w

  日期：2001.2

  benzophenone‐based farnesyltransferase inhibitors exploiting a novel aryl binding region in the farnesyltransferase's active site. The present study was mainly focussed on structural modifications of the trimethylene spacer of the 4‐phenyl butyroyl residue of our lead structure (IC50 = 530 nM). These modifications turned out to have little effect on activity as had the replacement of the terminal aryl by cyclohexyl

  我们描述了一类新的基于二苯甲酮的法呢基转移酶抑制剂，它利用法呢基转移酶活性位点中的新芳基结合区。本研究主要集中在我们先导结构的 4-苯基丁酰基残基的三亚甲基间隔基的结构修饰上（IC50 = 530 nM）。事实证明，这些修饰对活性几乎没有影响，因为末端芳基被环己基取代（IC50 = 440 nM 对 IC50 = 530 nM）。
• Non-thiol farnesyltransferase inhibitors: N-(4-tolylacetylamino-3-benzoylphenyl)-3-arylfurylacrylic acid amides
  作者：Andreas Mitsch、Pia Wißner、Katrin Silber、Peter Haebel、Isabel Sattler、Gerhard Klebe、Martin Schlitzer

  DOI：10.1016/j.bmc.2004.07.010

  日期：2004.9

  We have designed arylfurylacryl-substituted benzophenones as non-thiol farnesyltransferase inhibitors utilizing a novel aryl binding site of farnesyltransferase. These compounds display activity in the low nanomolar range.

  我们已经设计了芳基呋喃基丙烯酸取代的二苯甲酮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。这些化合物在低纳摩尔范围内显示活性。