4-氨基-3-羟基苯甲酰胺 | 146224-62-6

• 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-氨基-3-羟基苯甲酰胺
• 英文名称: 4-amino-3-hydroxybenzamide
• 英文别名: 5-aminocarbonyl-2-amino phenol
• CAS: 146224-62-6
• 化学式: C₇H₈N₂O₂
• 分子量: 152.153
• InChiKey: GLJFZIKVMDSXMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  89.3
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-氨基-3-羟基苯甲酰胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 丙酮 为溶剂， 反应 28.0h， 生成 (R)-4-((8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl)amino)-3-(2-hydroxyethoxy)benzamide
  参考文献：
  名称：

  Structure-based design and SAR development of novel selective polo-like kinase 1 inhibitors having the tetrahydropteridin scaffold

  摘要：

  Polo-like kinase 1 (Plk1) is a validated target for the treatment of cancer. In this report, by analyzing amino acid residue differences among the ATP-binding pockets of Plk1, P1k2 and Plk3, novel selective Plk1 inhibitors were designed based on BI 2536 and BI 6727, two Plk1 inhibitors in clinical studies for cancer treatments. The Plkl inhibitors reported herein have more potent inhibition against Plk1 and better isoform selectivity in the Plk family than these two lead compounds. In addition, by introducing a hydroxyl group, our compounds have significantly improved solubility and may target specific polar residues Arg57, Glu69 and Arg134 of Plk1. Moreover, most of our compounds exhibited antitumor activities in the nanomolar range against several cancer cell lines in the MTT assay. Through this structure-based design strategy and SAR study, a few promising selective Plk1 inhibitors having the tetrahy-dropteridin scaffold, for example, L34, were identified and could be for further anticancer research. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111769
• 作为产物：
  描述：

  3-羟基-4-硝基苯甲酸 在 铁粉 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 4-氨基-3-羟基苯甲酰胺
  参考文献：
  名称：

  Structure-based design and SAR development of novel selective polo-like kinase 1 inhibitors having the tetrahydropteridin scaffold

  摘要：

  Polo-like kinase 1 (Plk1) is a validated target for the treatment of cancer. In this report, by analyzing amino acid residue differences among the ATP-binding pockets of Plk1, P1k2 and Plk3, novel selective Plk1 inhibitors were designed based on BI 2536 and BI 6727, two Plk1 inhibitors in clinical studies for cancer treatments. The Plkl inhibitors reported herein have more potent inhibition against Plk1 and better isoform selectivity in the Plk family than these two lead compounds. In addition, by introducing a hydroxyl group, our compounds have significantly improved solubility and may target specific polar residues Arg57, Glu69 and Arg134 of Plk1. Moreover, most of our compounds exhibited antitumor activities in the nanomolar range against several cancer cell lines in the MTT assay. Through this structure-based design strategy and SAR study, a few promising selective Plk1 inhibitors having the tetrahy-dropteridin scaffold, for example, L34, were identified and could be for further anticancer research. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111769

文献信息

• [EN] METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION<br/>[FR] MÉTHODES ET COMPOSÉS POUR LA RESTAURATION DE LA FONCTION DU P53 MUTANT
  申请人：PMV PHARMACEUTICALS INC

  公开号：WO2021061643A1

  公开（公告）日：2021-04-01

  Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

  癌基因和肿瘤抑制基因的突变促成了癌症的发展和进展。本公开披露描述了一种恢复p53突变体野生型功能的化合物和方法。本发明的化合物可以结合突变型p53，并恢复p53突变体结合DNA并激活参与肿瘤抑制的下游效应子的能力。所披露的化合物可用于减少含有p53突变的癌症的进展。
• IL-8 receptor antagonists
  申请人：SmithKline Beecham Corporation

  公开号：US05886044A1

  公开（公告）日：1999-03-23

  This invention relates to the novel use of phenyl ureas in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).

  这项发明涉及苯基脲化合物在治疗由趋化因子白细胞介素-8（IL-8）介导的疾病状态中的新用途。
• [EN] NEW DIAZASPIROCYCLOALKANE AND AZASPIROCYCLOALKANE<br/>[FR] NOUVEAUX COMPOSÉS DIAZASPIROCYCLOALCANE ET AZASPIROCYCLOALCANE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013186159A1

  公开（公告）日：2013-12-19

  The invention provides novel compounds having the general formula (I), wherein R1, R2, Y and W are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有一般公式（I）的新化合物，其中R1、R2、Y和W如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。
• NEW DIAZASPIROCYCLOALKANE AND AZASPIROCYCLOALKANE
  申请人：Hoffmann-La Roche Inc.

  公开号：US20150099734A1

  公开（公告）日：2015-04-09

  The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , Y and W are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有一般化学式（I）的新化合物，其中R1、R2、Y和W如本文所述，包括该化合物的组合物以及使用该化合物的方法。
• Discovery of new ATP-competitive inhibitors of human DNA topoisomerase IIα through screening of bacterial topoisomerase inhibitors
  作者：Žiga Skok、Martina Durcik、Darja Gramec Skledar、Michaela Barančoková、Lucija Peterlin Mašič、Tihomir Tomašič、Anamarija Zega、Danijel Kikelj、Nace Zidar、Janez Ilaš

  DOI：10.1016/j.bioorg.2020.104049

  日期：2020.9

  Human DNA topoisomerase II is one of the major targets in anticancer therapy, however ATP-competitive inhibitors of this target have not yet reached their full potential. ATPase domain of human DNA topoisomerase II belongs to the GHKL ATPase superfamily and shares a very high 3D structural similarity with other superfamily members, including bacterial topoisomerases. In this work we report the discovery

  人类DNA拓扑异构酶II是抗癌治疗的主要靶标之一，但是该靶标的ATP竞争性抑制剂尚未发挥其全部潜力。人类DNA拓扑异构酶II的ATPase域属于GHKL ATPase超家族，与包括细菌拓扑异构酶在内的其他超家族成员具有非常高的3D结构相似性。在这项工作中，我们报告了通过筛选细菌DNA促旋酶和拓扑异构酶IV的ATP竞争性抑制剂的内部文库而发现的人类DNA拓扑异构酶IIα的ATP竞争性抑制剂的新化学型。系统筛选该文库为我们提供了20种热门化合物。选择了1,2,4-取代的N-苯基吡咯酰胺进行进一步的研究，结果得到了13种新的类似物，包括52在松弛试验（IC 50  = 3.2 µM）和ATPase分析（IC 50  = 0.43 µM）中具有强活性。在MCF-7癌细胞系中测定了所有命中的细胞毒活性，最有效的化合物16和20的IC 50值分别为8.7和8.2 µM。