N-(3-cyanophenyl)-4-[4-[(3-cyanophenyl)carbamoyl]phenyl]benzamide | 1613366-34-9

• 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-cyanophenyl)-4-[4-[(3-cyanophenyl)carbamoyl]phenyl]benzamide
• CAS: 1613366-34-9
• 化学式: C₂₈H₁₈N₄O₂
• 分子量: 442.477
• InChiKey: XPINDVLFCAWHQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(3-cyanophenyl)-4-[4-[(3-cyanophenyl)carbamoyl]phenyl]benzamide 在 劳森试剂 、 吡啶 、 sodium hydrosulfide hydrate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 72.0h， 生成 N-[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-4-[4-[[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]carbamothioyl]phenyl]benzenecarbothioamide
  参考文献：
  名称：

  Antibacterial Drug Leads: DNA and Enzyme Multitargeting

  摘要：

  We report the results of an investigation of the activity of a series of amidine and bisamidine compounds against Staphylococcus aureus and Escherichia coli. The most active compounds bound to an AT-rich DNA dodecamer (CGCGAATTCGCG)(2) and using DSC were found to increase the melting transition by up to 24 degrees C. Several compounds also inhibited undecaprenyl diphosphate synthase (UPPS) with IC50 values of 100-500 nM, and we found good correlations (R-2 = 0.89, S. aureus; R-2 = 0.79, E. coli) between experimental and predicted cell growth inhibition by using DNA Delta(Tm) and UPPS IC50 experimental results together with one computed descriptor. We also solved the structures of three bisamidines binding to DNA as well as three UPPS structures. Overall, the results are of general interest in the context of the development of resistance-resistant antibiotics that involve multitargeting.

  DOI：

  10.1021/jm501449u
• 作为产物：
  描述：

  间氨基苯甲腈 、 4,4'-苯偶酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 N-(3-cyanophenyl)-4-[4-[(3-cyanophenyl)carbamoyl]phenyl]benzamide
  参考文献：
  名称：

  [EN] ANTIBACTERIAL COMPOUNDS TARGETING ISOPRENOID BIOSYNTHESIS
  [FR] COMPOSÉS ANTIBACTÉRIENS CIBLANT LA BIOSYNTHÈSE D'ISOPRÉNOÏDE

  摘要：

  随着对甲氧西林等抗生素的耐药性增加，需要新药物。该发明提供了能够通过与结合口袋相互作用来抑制细胞药物靶标如UPPS和FPPS的小分子，从而阻止酶功能的药物。本文描述的化合物还对金黄色葡萄球菌具有活性（MIC90约为0.25 µg/mL），可以与甲氧西林强有力地协同作用（分数抑制浓度指数=0.25），并且在小鼠感染模型中具有保护作用。因此，该发明提供了许多化合物用于抗菌治疗，并通过联合疗法恢复对甲氧西林等药物的敏感性。

  公开号：

  WO2014089226A1

文献信息

• [EN] ANTIBACTERIAL COMPOUNDS TARGETING ISOPRENOID BIOSYNTHESIS<br/>[FR] COMPOSÉS ANTIBACTÉRIENS CIBLANT LA BIOSYNTHÈSE D'ISOPRÉNOÏDE
  申请人：UNIV ILLINOIS

  公开号：WO2014089226A1

  公开（公告）日：2014-06-12

  With the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. The invention provides small molecules that inhibit cellular drug targets such as UPPS and FPPS by interacting with binding pockets, thereby preventing enzyme function. Compounds described herein are also active against Staphylococcus aureus (MIC90 ~0.25 µg/mL), can potently synergize with methicillin (fractional inhibitory concentration index = 0.25), and are protective in a mouse infection model. The invention therefore provides numerous compounds for anti-bacterial treatments and for restoring sensitivity to drugs such as methicillin, using combination therapies.

  随着对甲氧西林等抗生素的耐药性增加，需要新药物。该发明提供了能够通过与结合口袋相互作用来抑制细胞药物靶标如UPPS和FPPS的小分子，从而阻止酶功能的药物。本文描述的化合物还对金黄色葡萄球菌具有活性（MIC90约为0.25 µg/mL），可以与甲氧西林强有力地协同作用（分数抑制浓度指数=0.25），并且在小鼠感染模型中具有保护作用。因此，该发明提供了许多化合物用于抗菌治疗，并通过联合疗法恢复对甲氧西林等药物的敏感性。
• ANTIBACTERIAL COMPOUNDS TARGETING ISOPRENOID BIOSYNTHESIS
  申请人：THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

  公开号：US20160039857A1

  公开（公告）日：2016-02-11

  With the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. The invention provides small molecules that inhibit cellular drug targets such as UPPS and FPPS by interacting with binding pockets, thereby preventing enzyme function. Compounds described herein are also active against Staphylococcus aureus (MIC90˜0.25 μg/mL), can potently synergize with methicillin (fractional inhibitory concentration index=0.25), and are protective in a mouse infection model. The invention therefore provides numerous compounds for anti-bacterial treatments and for restoring sensitivity to drugs such as methicillin, using combination therapies.

  随着对甲氧西林等抗生素的耐药性增加，需要新的药物。本发明提供了能够通过与结合口袋相互作用来抑制细胞药物靶点（如UPPS和FPPS）的小分子，从而防止酶功能的药物。本文所描述的化合物也对金黄色葡萄球菌（MIC90˜0.25 μg/mL）具有活性，能够与甲氧西林强烈协同作用（分数抑制浓度指数=0.25），并在小鼠感染模型中具有保护作用。因此，本发明提供了许多用于抗菌治疗和通过联合疗法恢复对甲氧西林等药物的敏感性的化合物。
• US9951097B2
  申请人：——

  公开号：US9951097B2

  公开（公告）日：2018-04-24
• Antibacterial Drug Leads: DNA and Enzyme Multitargeting
  作者：Wei Zhu、Yang Wang、Kai Li、Jian Gao、Chun-Hsiang Huang、Chun-Chi Chen、Tzu-Ping Ko、Yonghui Zhang、Rey-Ting Guo、Eric Oldfield

  DOI：10.1021/jm501449u

  日期：2015.2.12

  We report the results of an investigation of the activity of a series of amidine and bisamidine compounds against Staphylococcus aureus and Escherichia coli. The most active compounds bound to an AT-rich DNA dodecamer (CGCGAATTCGCG)(2) and using DSC were found to increase the melting transition by up to 24 degrees C. Several compounds also inhibited undecaprenyl diphosphate synthase (UPPS) with IC50 values of 100-500 nM, and we found good correlations (R-2 = 0.89, S. aureus; R-2 = 0.79, E. coli) between experimental and predicted cell growth inhibition by using DNA Delta(Tm) and UPPS IC50 experimental results together with one computed descriptor. We also solved the structures of three bisamidines binding to DNA as well as three UPPS structures. Overall, the results are of general interest in the context of the development of resistance-resistant antibiotics that involve multitargeting.