2-(4-(trifluoromethyl)phenyl-sulfonyl-carbamoyl)benzeneammoniumchloride | 1251932-83-8

• 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: 2-(4-(trifluoromethyl)phenyl-sulfonyl-carbamoyl)benzeneammoniumchloride
• CAS: 1251932-83-8
• 化学式: C₁₄H₁₁F₃N₂O₃S*ClH
• 分子量: 380.775
• InChiKey: WYUNJGSXWCRJRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.83
• 重原子数：
  24.0
• 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：

  2-(4-(trifluoromethyl)phenyl-sulfonyl-carbamoyl)benzeneammoniumchloride 、 在 吡啶 、 三氯氧磷 作用下， 反应 1.5h， 以61 mg的产率得到2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(naphthalen-2-ylmethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide
  参考文献：
  名称：

  Achiral Pyrazinone-Based Inhibitors of the Hepatitis C Virus NS3 Protease and Drug-Resistant Variants with Elongated Substituents Directed Toward the S2 Pocket

  摘要：

  Herein we describe the design, synthesis, inhibitory potency, and pharmacokinetic properties of a novel class of achiral peptidomimetic HCV NS3 protease inhibitors. The compounds are based on a dipeptidomimetic pyrazinone glycine P3P2 building block in combination with an aromatic acyl sulfonamide in the P1P1' position. Structure-activity relationship data and molecular modeling support occupancy of the S2 pocket from elongated R-6 substituents on the 2(1H)-pyrazinone core and several inhibitors with improved inhibitory potency down to K-i = 0.11 mu M were identified. A major goal with the design was to produce inhibitors structurally dissimilar to the di- and tripeptide-based HCV protease inhibitors in advanced stages of development for which cross-resistance might be an issue. Therefore, the retained and improved inhibitory potency against the drug-resistant variants A156T, D168V, and R155K further strengthen the potential of this class of inhibitors. A number of the inhibitors were tested in in vitro preclinical profiling assays to evaluate their apparent pharmacokinetic properties. The various R6 substituents were found to have a major influence on solubility, metabolic stability, and cell permeability.

  DOI：

  10.1021/jm301887f
• 作为产物：
  描述：

  t-butyl 2-(4-(trifluoromethyl)phenylsulfonyl-carbamoyl)phenylcarbamate 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以100%的产率得到2-(4-(trifluoromethyl)phenyl-sulfonyl-carbamoyl)benzeneammoniumchloride
  参考文献：
  名称：

  基于R 3延长的吡嗪酮支架的丙型肝炎病毒的Pan-NS3蛋白酶抑制剂

  摘要：

  在本文中，我们介绍了基于2（1 H）-吡嗪酮的HCV NS3蛋白酶抑制剂的设计和合成，并显示了延长的R 3尿素取代基与几种NS3蛋白变体的抑制能力增强相关。据信抑制剂依赖于模拟氢键的β-折叠，该氢键在不同的基因型和当前的抗药性变体上是相似的，并且对应于天然肽底物的β-折叠相互作用。例如，具有包括环状酰亚胺的尿素取代基的抑制剂36对基因型1a，野生型（K i  = 30 nM）和R155K（K i  = 2 nM）和基因型3a（Ki  = 5 nM）。

  DOI：

  10.1016/j.ejmech.2018.02.032

文献信息

• Discovery of achiral inhibitors of the hepatitis C virus NS3 protease based on 2(1H)-pyrazinones
  作者：Pernilla Örtqvist、Johan Gising、Angelica E. Ehrenberg、Aparna Vema、Anneli Borg、Anders Karlén、Mats Larhed、U. Helena Danielson、Anja Sandström

  DOI：10.1016/j.bmc.2010.06.101

  日期：2010.9

  Herein, the design, synthesis and inhibitory potency of a series of novel hepatitis C virus (HCV) NS3 protease inhibitors are presented. These inhibitors are based on a 2(1H)-pyrazinone P3 scaffold in combination with either a P2 phenylglycine or a glycine, and they were evaluated on the wild type as well as on two resistant variants of the enzyme, A156T and D168V. Molecular modelling suggested that the aromatic side-chain of the P2 phenylglycine occupies the same space as the substituent in position 6 on the pyrazinone core. The versatile synthetic route applied for the pyrazinone synthesis made a switch between the two positions easily feasible, resulting in phenyl-or benzyl substituted pyrazinones and leaving glycine as the P2 residue. Of several P1-P1' residues evaluated, an aromatic P1-P1' scaffold was found superior in combination with the new P3-P2 building block. As a result, an entirely new type of achiral and rigidified inhibitors was discovered, with the best of the novel inhibitors having fourfold improved potency compared to the corresponding tripeptide lead. We consider these achiral inhibitors highly suitable as starting points for further optimization. (C) 2010 Elsevier Ltd. All rights reserved.