N-(3-benzoyl-4-(2-p-tolylacetamido)phenyl)-3-(5-(4-nitrophenyl)furan-2-yl)acrylamide | 493037-30-2

• 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-(3-benzoyl-4-(2-p-tolylacetamido)phenyl)-3-(5-(4-nitrophenyl)furan-2-yl)acrylamide
• 英文别名: (E)-N-[3-benzoyl-4-[[2-(4-methylphenyl)acetyl]amino]phenyl]-3-[5-(4-nitrophenyl)furan-2-yl]prop-2-enamide
• CAS: 493037-30-2
• 化学式: C₃₅H₂₇N₃O₆
• 分子量: 585.616
• InChiKey: ZTORJVQLJHBZSP-LVZFUZTISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  44
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-benzoyl-4-(2-p-tolylacetamido)phenyl)-3-(5-(4-nitrophenyl)furan-2-yl)acrylamide 在 tin(ll) chloride 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以89%的产率得到(E)-3-[5-(4-aminophenyl)furan-2-yl]-N-[3-benzoyl-4-[[2-(4-methylphenyl)acetyl]amino]phenyl]prop-2-enamide
  参考文献：
  名称：

  非硫醇法呢基转移酶抑制剂：N-（4-甲苯基乙酰氨基-3-苯甲酰基苯基）-3-芳基呋喃基丙烯酸酰胺。

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2004.07.010
• 作为产物：
  描述：

  3-<5-(4-Nitrophenyl)-2-furyl>propenoic acid 在 氯化亚砜 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 4.0h， 生成 N-(3-benzoyl-4-(2-p-tolylacetamido)phenyl)-3-(5-(4-nitrophenyl)furan-2-yl)acrylamide
  参考文献：
  名称：

  非硫醇法呢基转移酶抑制剂：N-（4-酰基氨基-3-苯甲酰基苯基）-3- [5-（4-硝基苯基）-2-呋喃基]丙烯酸酰胺。

  摘要：

  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。

  DOI：

  10.1016/s0968-0896(03)00064-6

文献信息

• 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。
• Exploration of Novel Aryl Binding Sites of Farnesyltransferase Using Molecular Modeling and Benzophenone-Based Farnesyltransferase Inhibitors
  作者：Markus Böhm、Andreas Mitsch、Pia Wissner、Isabel Sattler、Martin Schlitzer

  DOI：10.1021/jm010873j

  日期：2001.9.1

  suggest being the postulated aryl binding sites. One aryl binding region is located in close proximity to the zinc ion and is defined by the aromatic side chains of Tyr 300beta, Trp 303beta, Tyr 361beta, and Tyr 365beta. The second aryl binding site is defined by the side chains of Tyr 300beta, Leu 295beta, Lys 294beta, Lys 353beta, and Lys 356beta. This second aryl binding site has been used for the design

  大多数非硫醇CAAX拟肽法呢基转移酶抑制剂具有取代端半胱氨酸的含氮杂环，该半胱氨酸应与酶结合的锌配位。然而，已经表明那些含氮杂环可以被不能配位锌离子的碳环芳族部分所取代，这一结论导致假定了一个或两个迄今未知的芳基结合位点。这些新的结合位点的空间位置尚未给出任何指示。利用文献中已知的几种非硫醇法呢基转移酶抑制剂和一些基于我们的二苯甲酮骨架的模型化合物进行灵活对接，并进行GRID搜索，我们在法呢基转移酶中鉴定了两个区域 我们建议是假定的芳基结合位点的活性位点。一个芳基结合区位于紧邻锌离子的位置，并由Tyr 300beta，Trp 303beta，Tyr 361beta和Tyr 365beta的芳族侧链定义。第二芳基结合位点由Tyr 300beta，Leu 295beta，Lys 294beta，Lys 353beta和Lys 356beta的侧链定义。此第二个芳基结合位点已用于设计IC（50）为35
• Structure–Activity relationships of novel anti-Malarial agents. Part 4: N-(3-Benzoyl-4-tolylacetylaminophenyl)-3-(5-aryl-2-furyl)acrylic acid amides
  作者：Jochen Wiesner、Andreas Mitsch、Pia Wißner、Oliver Krämer、Hassan Jomaa、Martin Schlitzer

  DOI：10.1016/s0960-894x(02)00555-3

  日期：2002.10

  In a previous report, we have described novel anti-malarial compounds based on a 2,5-diaminobenzophenone scaffold. Here, we have invesigated acryloyl derivatives carrying a biaryl structure consisting of a terminal aryl residue and a central 2-furyl ring. Several compounds were obtained in the series of para-substituted phenylfurylacryloyl derivatives that displayed improved anti-malarial activity in comparison to earlier described derivatives. From the structure-activity relationships it can be deduced that there has to be a lipophilic moiety in the para-position of the terminal phenyl residue. Furthermore, there are indications that, alternatively, activity may benefit from the presence of a polar moiety with hydrogen bond acceptor properties. (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.
• 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。