4-[(4-氰基苯甲酰基)氨基]苯甲酸 | 143330-23-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-[(4-氰基苯甲酰基)氨基]苯甲酸
• 英文名称: 4-[(4-cyanobenzoyl)amino]benzoic acid
• 英文别名: 4-(4-cyanobenzamido)benzoic acid；Benzoic acid, 4-[(4-cyanobenzoyl)amino]-
• CAS: 143330-23-8
• 化学式: C₁₅H₁₀N₂O₃
• 分子量: 266.256
• InChiKey: GFXSULKPXYKIGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(4-氰基苯甲酰基)氨基]苯甲酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 4-cyano-N-[4-[[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]carbamoyl]phenyl]benzamide
  参考文献：
  名称：

  Design, synthesis and insulin-sensitising effects of novel PTP1B inhibitors

  摘要：

  Fifteen novel sulfathiazole-related compounds were designed as PTP1B inhibitors based on a previously reported allosteric inhibitor (1) of PTP1B. These compounds were synthesized and evaluated against human recombinant PTP1B. Six compounds (3, 4, 8 and 14-16) exhibited significant inhibitory activity against PTP1B. The most active compound (16) showed IC50 value of 3.2 mu M and kinetic analysis indicated that it is a non-competitive inhibitor of PTP1B. Furthermore, compound 16 demonstrated excellent selectivity to PTP1B over other PTPs. It also displayed in vivo insulin sensitizing effect in the insulin resistant mice. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.073
• 作为产物：
  描述：

  对氰基苯甲酰氯 在 碳酸氢钠 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 6.0h， 生成 4-[(4-氰基苯甲酰基)氨基]苯甲酸
  参考文献：
  名称：

  Scalable Syntheses of Methoxyaspartate and Preparation of the Antibiotic Cystobactamid 861-2 and Highly Potent Derivatives

  摘要：

  An improved scalable synthesis of orthogonally functionalized methoxyaspartate, the chiral hinge region element in cystobactamids, is reported. This improvement sets the stage for the total synthesis of four new cystobactamids along with cystobactamid 861-2, whose antibacterial properties are determined and compared. The cyano derivative of cystobactamide 861-2 shows superior antibacterial activity against Gram-negative bacteria to any natural cystobactamide tested so far.

  DOI：

  10.1021/acs.orglett.9b03143

文献信息

• Antiallergic and cytoprotective activity of new N-phenylbenzamido acid derivatives.
  作者：Francesco Makovec、Walter Peris、Laura Revel、Roberto Giovanetti、Daniele Redaelli、Lucio C. Rovati

  DOI：10.1021/jm00098a006

  日期：1992.10

  A series of new N-phenylbenzamido acid derivatives was synthesized and evaluated for their ability to inhibit the IgE-mediated passive cutaneous anaphylaxis in the rat (PCA), as well as for their capacity to inhibit gastric mucosal damage induced by the oral administration of absolute alcohol in the rat. Some of these new derivatives exhibit potent antiallergic and cytoprotective activity, 20-80 times

  合成了一系列新的N-苯基苯甲酰胺酸衍生物，并评估了它们抑制IgE介导的大鼠被动皮肤过敏反应（PCA）的能力，以及它们抑制口服绝对剂量诱导的胃粘膜损伤的能力。大鼠饮酒。这些新衍生物中的一些表现出有效的抗过敏和细胞保护活性，比参考的糖基葡萄糖酸二钠（DSCG）高20-80倍。讨论了构效关系。该系列中更有效的化合物之一，即4-（1H-四唑-5-基）-N- [4-（1H-四唑-5-基）苯基]苯甲酰胺的抗过敏活性（化合物44，CR 2039 ）在体内进行了进一步评估。该化合物拮抗雾化的卵清蛋白在麻醉的和有意识的IgE致敏豚鼠中引起的支气管收缩，ID50为3.7 mg /动物（气管吹入）和20 mg / kg（im）。在空腹动物急性口服高渗氯化钠溶液或乙酸引起的胃溃疡模型中，评估了进一步的细胞保护作用。在实验中使用的模型中，CR 2039是有效的，而DSCG似乎没有任何保护活性。这种有效的抗过敏和粘膜
• Synthetic and Biological Studies on New Urea and Triazole Containing Cystobactamid Derivatives
  作者：Therese Planke、Katarina Cirnski、Jennifer Herrmann、Rolf Müller、Andreas Kirschning

  DOI：10.1002/chem.201904073

  日期：2020.4

  Cystobactamid 861-2 is the most active member of these antibiotics. Most amide bonds present in the cystobactamids link benzoic acids with anilines and it was found that some of these amide bonds undergo chemical and enzymatic hydrolysis, especially the one linking ring C with ring D. This work reports on the chemical synthesis and biological evaluation of thirteen new cystobactamids that still contain

  Cystobactamids 属于基于芳烃的低聚酰胺类，可有效抑制细菌 IIa 型拓扑异构酶。Cystobactamid 861-2 是这些抗生素中最活跃的成员。大多数存在于cystobactamids 的酰胺键将苯甲酸与苯胺连接起来，并且发现其中一些酰胺键经历化学和酶水解，尤其是连接环C 和环D 的一个。这项工作报告了13 个的化学合成和生物学评价仍包含甲氧基天冬氨酸铰链的新型囊菌酰胺。然而，在后一种情况下，我们通过脲或三唑基团和修饰的环 A 交换了选定的酰胺键。虽然这些结构替代物可以提高水解稳定性，但囊菌酰胺 861-2 的高抗菌效力只能在特定情况下保留。
• [EN] NOVEL CYSTOBACTAMIDE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE CYSTOBACTAMIDES
  申请人：HELMHOLTZ ZENTRUM INFEKTIONSFORSCHUNG GMBH

  公开号：WO2019038405A1

  公开（公告）日：2019-02-28

  The present invention relates to novel derivatives of cystobactamides of formula (lb) and the use thereof for the treatment or prophylaxis of bacterial infections.

  本发明涉及公式（lb）的半胱菌肽的新颖衍生物及其用于治疗或预防细菌感染的用途。
• Activity of diimidazoline amides against African trypanosomiasis
  作者：Yuxiang Dong、Xiaofang Wang、Monica Cal、Marcel Kaiser、Jonathan L. Vennerstrom

  DOI：10.1016/j.bmcl.2013.12.064

  日期：2014.2

  diimidazoline mono- and diamides that were as potent as pentamidine against Trypanosoma brucei rhodesiense in vitro. All of these were also less cytotoxic than pentamidine, but none was as effective as the latter in a T. brucei rhodesiense-infected mouse model. A single imidazoline may be sufficient for high antitrypanosomal activity provided that a second weak base functional group is present.

  我们在体外鉴定了几种二咪唑啉单酰胺和二酰胺，它们与喷他脒对罗得西亚布氏锥虫一样有效。所有这些也比喷他脒的细胞毒性更小，但在罗得西亚布氏锥虫感染的小鼠模型中，没有一种比喷他脒更有效。如果存在第二个弱碱官能团，单个咪唑啉可能足以获得高抗锥虫活性。
• Is Simultaneous Binding to DNA and Gyrase Important for the Antibacterial Activity of Cystobactamids?
  作者：Danny Solga、Lianne H. E. Wieske、Scott Wilcox、Carsten Zeilinger、Linda Jansen‐Olliges、Katarina Cirnski、Jennifer Herrmann、Rolf Müller、Mate Erdelyi、Andreas Kirschning

  DOI：10.1002/chem.202303796

  日期：2024.4.2

  Cystobactamids are aromatic oligoamides that exert their natural antibacterial properties by inhibition of bacterial gyrases. Such aromatic oligoamides were proposed to inhibit α‐helix‐mediated protein‐protein interactions and may serve for specific recognition of DNA. Based on this suggestion, we designed new derivatives that have duplicated cystobactamid triarene units as model systems to decipher the specific binding mode of cystobactamids to double stranded DNA. Solution NMR analyses revealed that natural cystobactamids as well as their elongated analogues show an overall bent shape at their central aliphatic unit, with an average CX‐CY‐CZ angle of ~110 degrees. Our finding is corroborated by the target‐bound structure of close analogues, as established by cryo‐EM very recently. Cystobactamid CN‐861‐2 binds directly to the bacterial gyrase with an affinity of 9 μM, and also exhibits DNA‐binding properties with specificity for AT‐rich DNA. Elongation/dimerization of the triarene subunit of native cystobactamids is demonstrated to lead to an increase in DNA binding affinity. This implies that cystobactamids’ gyrase inhibitory activity necessitates not just interaction with the gyrase itself, but also with DNA via their triarene unit.

  摘要胱杆菌酰胺是一种芳香族低聚酰胺，通过抑制细菌的回旋酶而发挥其天然抗菌特性。有人认为这种芳香族低聚酰胺可抑制α-螺旋介导的蛋白质与蛋白质之间的相互作用，并可用于 DNA 的特异性识别。基于这一观点，我们设计了具有重复的胱杆菌酰胺三芳基单元的新衍生物作为模型系统，以破译胱杆菌酰胺与双链 DNA 的特异性结合模式。溶液核磁共振分析表明，天然胱内酰胺及其拉长的类似物在其中央脂肪族单元处显示出整体弯曲的形状，平均 CX-CY-CZ 角约为 110 度。最近通过低温电子显微镜（cryo-EM）确定的近似类似物的靶结合结构也证实了我们的发现。胱杆菌酰胺 CN-861-2 可直接与细菌回旋酶结合，亲和力为 9 μM，还具有 DNA 结合特性，对富含 AT 的 DNA 有特异性。事实证明，原生胱内酰胺的三烯亚基伸长/二聚化会导致 DNA 结合亲和力的增加。这意味着胱巴坦类药物的回旋酶抑制活性不仅需要与回旋酶本身相互作用，还需要通过其三芳邻单元与 DNA 相互作用。