3',5'-difluoro-3-nitro-[1,1'-biphenyl]-4-amine | 1352638-18-6

• 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: 3',5'-difluoro-3-nitro-[1,1'-biphenyl]-4-amine
• 英文别名: 3',5'-difluoro-3-nitrobiphenyl-4-ylamine；4-(3,5-Difluorophenyl)-2-nitroaniline
• CAS: 1352638-18-6
• 化学式: C₁₂H₈F₂N₂O₂
• 分子量: 250.205
• InChiKey: MBFBYFMVIQSXAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3',5'-difluoro-3-nitro-[1,1'-biphenyl]-4-amine 、 3,4,5-三甲氧基苯甲酰氯 在 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.42h， 以40%的产率得到N-(3’,5’-difluoro-3-nitrobiphenyl-4-yl)-3,4,5-trimethoxybenzamide
  参考文献：
  名称：

  Potent Galloyl-Based Selective Modulators Targeting Multidrug Resistance Associated Protein 1 and P-glycoprotein

  摘要：

  The multifactorial nature of chemotherapy failure in controlling cancer is often associated with the occurrence of multidrug resistance (MDR), a phenomenon likely related to the increased expression of members of the ATP binding cassette (ABC) transporter superfamily. In this respect, the most extensively characterized MDR transporters include ABCB1 (also known as MDR1 or P-glycoprotein) and ABCC1 (also known as MRP1) whose inhibition remains a priority to circumvent drug resistance. Herein, we report how the simple galloyl benzamide scaffold can be easily and properly decorated for the preparation of either MRP1 or P-gp highly selective inhibitors. In particular, some gallamides and pyrogallol-l-monomethyl ethers showed remarkable affinity and selectivity toward MRP1. On the other hand, trimethyl ether galloyl anilides, with few exceptions, exhibited moderate to very high and selective P-gp inhibition.

  DOI：

  10.1021/jm201305y
• 作为产物：
  描述：

  4-溴-2-硝基苯胺 、 3,5-二氟苯硼酸 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 7.0h， 以70%的产率得到3',5'-difluoro-3-nitro-[1,1'-biphenyl]-4-amine
  参考文献：
  名称：

  调查联苯烟酰胺的抗增殖活性的结构要求。

  摘要：

  筛选了许多以前作为渗透性糖蛋白（P-gp）调节剂研究过的三甲氧基苯甲酸酐，目的是鉴定新的抗癌药。选择对抗MCF-7细胞系具有抗增殖活性的这些化合物之一作为命中结构。为了克服溶解性问题，用烟酰基取代三甲氧基苯甲酰基部分导致了一系列新的N-联苯基烟酰基苯甲酰苯胺，其中包括硝基衍生物N-（3'，5'-二氟-3-硝基- [1,1'-联苯] -4-基）烟酰胺（3）在纳摩尔范围内显示出对MCF-7和MDA-MB-231细胞的抗增殖活性。寻找硝基的生物等排体导致腈类似物N-（3-氰基-4'-氟-[1,1'-联苯] -4-基）烟酰胺（36），表明对MCF-7和MDA-MB-231细胞的活性大大增强。化合物36诱导了G2期和M期MCF-7细胞群体的剂量依赖性积累，并减少了S期细胞。相对于长春花碱（一种众所周知的有效抗有丝分裂剂），化合物36在低剂量（20-40 nm）下也能诱导G1期阻滞，但不抑制体外微管蛋白的聚合。

  DOI：

  10.1002/cmdc.201700365

文献信息

• Trimethoxybenzanilide-Based P-Glycoprotein Modulators: An Interesting Case of Lipophilicity Tuning by Intramolecular Hydrogen Bonding
  作者：Piero Tardia、Angela Stefanachi、Mauro Niso、Diana Antonella Stolfa、Giuseppe Felice Mangiatordi、Domenico Alberga、Orazio Nicolotti、Gianluca Lattanzi、Angelo Carotti、Francesco Leonetti、Roberto Perrone、Francesco Berardi、Amalia Azzariti、Nicola Antonio Colabufo、Saverio Cellamare

  DOI：10.1021/jm500697c

  日期：2014.8.14

  One of the principal reasons for the chemotherapy failure is the overexpression of drug efflux pumps, ABCB1 (also known as MDR1 or P-gp) and ABCC1 (also known as MRP1), whose inhibition remains a priority to circumvent drug resistance. We have recently shown a clear trend between lipophilicity and P-glycoprotein inhibitory activity for a class of galloyl-based modulators targeting P-glycoprotein and MRP1. Herein we report a new series of polymethoxy benzamides, whose lipophilicity was modulated through the establishment of an intramolecular hydrogen bond (IMHB) which allows reaching of P-gp inhibitory activity at the submicromolar IC50 level. The present study provides a strong rationale for candidates in the presence of IMHB as a key element for a high P-gp inhibitory activity.
• Investigating Structural Requirements for the Antiproliferative Activity of Biphenyl Nicotinamides
  作者：Maria Majellaro、Angela Stefanachi、Piero Tardia、Chiara Vicenti、Angelina Boccarelli、Alessandra Pannunzio、Federica Campanella、Mauro Coluccia、Nunzio Denora、Francesco Leonetti、Modesto de Candia、Cosimo Damiano Altomare、Saverio Cellamare

  DOI：10.1002/cmdc.201700365

  日期：2017.8.22

  with the aim of identifying new anticancer agents. One of these compounds, which showed antiproliferative activity against resistant MCF-7 cell line, was selected as the hit structure. Replacement of the trimethoxybenzoyl moiety with a nicotinoyl group, in order to overcome solubility issues, led to a new series of N-biphenyl nicotinoyl anilides, among which a nitro derivative, N-(3',5'-difluoro-3-nitro-[1

  筛选了许多以前作为渗透性糖蛋白（P-gp）调节剂研究过的三甲氧基苯甲酸酐，目的是鉴定新的抗癌药。选择对抗MCF-7细胞系具有抗增殖活性的这些化合物之一作为命中结构。为了克服溶解性问题，用烟酰基取代三甲氧基苯甲酰基部分导致了一系列新的N-联苯基烟酰基苯甲酰苯胺，其中包括硝基衍生物N-（3'，5'-二氟-3-硝基- [1,1'-联苯] -4-基）烟酰胺（3）在纳摩尔范围内显示出对MCF-7和MDA-MB-231细胞的抗增殖活性。寻找硝基的生物等排体导致腈类似物N-（3-氰基-4'-氟-[1,1'-联苯] -4-基）烟酰胺（36），表明对MCF-7和MDA-MB-231细胞的活性大大增强。化合物36诱导了G2期和M期MCF-7细胞群体的剂量依赖性积累，并减少了S期细胞。相对于长春花碱（一种众所周知的有效抗有丝分裂剂），化合物36在低剂量（20-40 nm）下也能诱导G1期阻滞，但不抑制体外微管蛋白的聚合。
• Potent Galloyl-Based Selective Modulators Targeting Multidrug Resistance Associated Protein 1 and P-glycoprotein
  作者：Raffaella Zoe Pellicani、Angela Stefanachi、Mauro Niso、Angelo Carotti、Francesco Leonetti、Orazio Nicolotti、Roberto Perrone、Francesco Berardi、Saverio Cellamare、Nicola Antonio Colabufo

  DOI：10.1021/jm201305y

  日期：2012.1.12

  The multifactorial nature of chemotherapy failure in controlling cancer is often associated with the occurrence of multidrug resistance (MDR), a phenomenon likely related to the increased expression of members of the ATP binding cassette (ABC) transporter superfamily. In this respect, the most extensively characterized MDR transporters include ABCB1 (also known as MDR1 or P-glycoprotein) and ABCC1 (also known as MRP1) whose inhibition remains a priority to circumvent drug resistance. Herein, we report how the simple galloyl benzamide scaffold can be easily and properly decorated for the preparation of either MRP1 or P-gp highly selective inhibitors. In particular, some gallamides and pyrogallol-l-monomethyl ethers showed remarkable affinity and selectivity toward MRP1. On the other hand, trimethyl ether galloyl anilides, with few exceptions, exhibited moderate to very high and selective P-gp inhibition.