4-amino-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide | 1450789-68-0

• 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: 4-amino-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide
• CAS: 1450789-68-0
• 化学式: C₁₄H₁₁F₃N₂O₃S
• 分子量: 344.314
• InChiKey: HQOZQWKNGXWTEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.41
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  89.26
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-amino-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide 在 盐酸 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 cyclopentyl (1-(4-((6-methoxy-2-phenylpyrimidin-4-yl)oxy)-3-vinylphenyl)-2-oxo-2-((4-(((4-(trifluoromethyl)phenyl)sulfonyl)carbamoyl)phenyl)amino)ethyl)carbamate
  参考文献：
  名称：

  Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2–P1′ Region

  摘要：

  Herein, novel hepatitis C virus NS3/4A protease inhibitors based on a P2 pyrimidinyloxyphenylglycine in combination with various regioisomers of an aryl acyl sulfonamide functionality in P1 are presented. The P1' 4-(trifluoromethyl)phenyl side chain was shown to be particularly beneficial in terms of inhibitory potency. Several inhibitors with K i-values in the nanomolar range were developed and included identification of promising P3-truncated inhibitors spanning from P2-P1'. Of several different P2 capping groups that were evaluated, a preference for the sterically congested Boc group was revealed. The inhibitors were found to retain inhibitory potencies for A156T, D168V, and R155K variants of the protease. Furthermore, in vitro pharmacokinetic profiling showed several beneficial effects on metabolic stability as well as on apparent intestinal permeability from both P3 truncation and the use of the P1' 4-(trifluoromethyl)phenyl side chain.

  DOI：

  10.1021/ml400217r
• 作为产物：
  描述：

  4-三氟甲基苯磺酰胺 、 4-溴苯胺 、 molybdenum hexacarbonyl 在 trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II) 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.42h， 以62%的产率得到4-amino-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide
  参考文献：
  名称：

  Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2–P1′ Region

  摘要：

  Herein, novel hepatitis C virus NS3/4A protease inhibitors based on a P2 pyrimidinyloxyphenylglycine in combination with various regioisomers of an aryl acyl sulfonamide functionality in P1 are presented. The P1' 4-(trifluoromethyl)phenyl side chain was shown to be particularly beneficial in terms of inhibitory potency. Several inhibitors with K i-values in the nanomolar range were developed and included identification of promising P3-truncated inhibitors spanning from P2-P1'. Of several different P2 capping groups that were evaluated, a preference for the sterically congested Boc group was revealed. The inhibitors were found to retain inhibitory potencies for A156T, D168V, and R155K variants of the protease. Furthermore, in vitro pharmacokinetic profiling showed several beneficial effects on metabolic stability as well as on apparent intestinal permeability from both P3 truncation and the use of the P1' 4-(trifluoromethyl)phenyl side chain.

  DOI：

  10.1021/ml400217r

文献信息

• Discovery of pyrazinone based compounds that potently inhibit the drug-resistant enzyme variant R155K of the hepatitis C virus NS3 protease
  作者：Anna Karin Belfrage、Eldar Abdurakhmanov、Eva Åkerblom、Peter Brandt、Anna Oshalim、Johan Gising、Anna Skogh、Johan Neyts、U. Helena Danielson、Anja Sandström

  DOI：10.1016/j.bmc.2016.03.066

  日期：2016.6

  this series showed nanomolar potency against R155K NS3 protease; which generally confer resistance to all HCV NS3 protease inhibitors approved or in clinical trials. These results further strengthen the potential of this novel substance class, being very different to the approved drugs and clinical candidates, in the development of inhibitors less sensitive to drug resistance.

  在本文中，我们介绍了基于2（1H）-吡嗪酮的HCV NS3蛋白酶抑制剂的设计和合成，这些抑制剂在C端具有变化。使用野生型和抗药性酶变体R155K的基因型1a进行生化评估。令人惊讶的是，不含酸性磺酰胺的化合物仍具有良好的抑制作用，从而挑战了我们以前的分子对接模型。此外，该系列中的某些化合物显示出针对R155K 蛋白酶的纳摩尔效价；通常赋予所有已批准或正在临床试验中的HCV 蛋白酶抑制剂抗药性。这些结果进一步增强了这种新物质类别的潜力，这种新物质类别与批准的药物和临床候选药物非常不同，可用于开发对耐药性较不敏感的抑制剂。