2-[[5-Benzyl-6-chloro-3-oxo-4-[2-oxo-2-[2-[[4-(trifluoromethyl)phenyl]sulfonylcarbamoyl]anilino]ethyl]pyrazin-2-yl]amino]acetic acid | 1251933-59-1

• 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-[[5-Benzyl-6-chloro-3-oxo-4-[2-oxo-2-[2-[[4-(trifluoromethyl)phenyl]sulfonylcarbamoyl]anilino]ethyl]pyrazin-2-yl]amino]acetic acid
• CAS: 1251933-59-1
• 化学式: C₂₉H₂₃ClF₃N₅O₇S
• 分子量: 678.045
• InChiKey: RAUINXWYAUBXDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  183
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  、 2-(4-(trifluoromethyl)phenyl-sulfonyl-carbamoyl)benzeneammoniumchloride 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydrogen sulfate 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 68.0h， 以0.012 g的产率得到2-[[5-Benzyl-6-chloro-3-oxo-4-[2-oxo-2-[2-[[4-(trifluoromethyl)phenyl]sulfonylcarbamoyl]anilino]ethyl]pyrazin-2-yl]amino]acetic acid
  参考文献：
  名称：

  Discovery of achiral inhibitors of the hepatitis C virus NS3 protease based on 2(1H)-pyrazinones

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2010.06.101

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.