tert-butyl (1R,2S)-1-{[(phenylsulfonyl)amino]carbonyl}-2-vinylcyclopropylcarbamate | 905994-17-4

• 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: tert-butyl (1R,2S)-1-{[(phenylsulfonyl)amino]carbonyl}-2-vinylcyclopropylcarbamate
• 英文别名: tert-butyl N-[(1R,2S)-1-(benzenesulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamate
• CAS: 905994-17-4
• 化学式: C₁₇H₂₂N₂O₅S
• 分子量: 366.438
• InChiKey: QNCHJATVPJUVHY-SJKOYZFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (1R,2S)-1-{[(phenylsulfonyl)amino]carbonyl}-2-vinylcyclopropylcarbamate 在 盐酸 、 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 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl N-[(1S)-1-[[(1S)-2-[[(1R,2S)-1-(benzenesulfonylcarbamoyl)-2-vinyl-cyclopropyl]amino]-1-[4-[(7-methoxy-2-phenyl-4-quinolyl)oxy]phenyl]-2-oxo-ethyl]carbamoyl]-2,2-dimethyl-propyl]carbamate
  参考文献：
  名称：

  Phenylglycine as a novel P2 scaffold in hepatitis C virus NS3 protease inhibitors

  摘要：

  Molecular modeling and inhibitory potencies of tetrapeptide protease inhibitors of HCV NS3 proposed phenylglycine as a new promising P2 residue. The results suggest that phenylglycine might be capable of interacting with the NS3 (protease-helicase/ NTPase) in ways not possible for the common P2 proline-based inhibitors. Thus, a series of tripeptides, both linear and macrocyclic, based on p-hydroxy-phenylglycine in the P2 position were prepared and their inhibitory effect determined. When the p-hydroxy group was replaced by methoxy, isoquinolin-, or quinolinyloxy functions, inhibitors with improved potencies were obtained. The P2 phenylglycine-based inhibitors were further optimized by C-terminal extension to acyl sulfonamides and by P1-P3 cyclization, which gave products with inhibition constants in the nanomolar range (similar to 75 nM). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.003
• 作为产物：
  描述：

  苯磺酰胺 、 (1R,2S)-1-叔丁氧羰基氨基-2-乙烯基环丙烷甲酸 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 以62%的产率得到tert-butyl (1R,2S)-1-{[(phenylsulfonyl)amino]carbonyl}-2-vinylcyclopropylcarbamate
  参考文献：
  名称：

  Phenylglycine as a novel P2 scaffold in hepatitis C virus NS3 protease inhibitors

  摘要：

  Molecular modeling and inhibitory potencies of tetrapeptide protease inhibitors of HCV NS3 proposed phenylglycine as a new promising P2 residue. The results suggest that phenylglycine might be capable of interacting with the NS3 (protease-helicase/ NTPase) in ways not possible for the common P2 proline-based inhibitors. Thus, a series of tripeptides, both linear and macrocyclic, based on p-hydroxy-phenylglycine in the P2 position were prepared and their inhibitory effect determined. When the p-hydroxy group was replaced by methoxy, isoquinolin-, or quinolinyloxy functions, inhibitors with improved potencies were obtained. The P2 phenylglycine-based inhibitors were further optimized by C-terminal extension to acyl sulfonamides and by P1-P3 cyclization, which gave products with inhibition constants in the nanomolar range (similar to 75 nM). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.003

文献信息

• US7323447B2
  申请人：——

  公开号：US7323447B2

  公开（公告）日：2008-01-29
• [EN] HEPATITIS C VIRUS INHIBITORS<br/>[FR] INHIBITEURS DU VIRUS DE L'HEPATITE C
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2006086381A2

  公开（公告）日：2006-08-17

  [EN] The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which inhibit the function of the NS3 protease (also referred to herein as "serine protease") encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS3 protease.
  [FR] La présente invention concerne de manière générale des composés antiviraux et, plus spécifiquement, des composés inhibant la fonction de la protéase NS3 (également désignée sous le nom de "sérine protéase") codée par le virus de l'hépatite C (VHC), des compositions contenant lesdits composés, et des méthodes d'inhibition de la fonction de la protéase NS3.
• Phenylglycine as a novel P2 scaffold in hepatitis C virus NS3 protease inhibitors
  作者：Pernilla Örtqvist、Shane D. Peterson、Eva Åkerblom、Thomas Gossas、Yogesh A. Sabnis、Rebecca Fransson、Gunnar Lindeberg、U. Helena Danielson、Anders Karlén、Anja Sandström

  DOI：10.1016/j.bmc.2006.11.003

  日期：2007.2.1

  Molecular modeling and inhibitory potencies of tetrapeptide protease inhibitors of HCV NS3 proposed phenylglycine as a new promising P2 residue. The results suggest that phenylglycine might be capable of interacting with the NS3 (protease-helicase/ NTPase) in ways not possible for the common P2 proline-based inhibitors. Thus, a series of tripeptides, both linear and macrocyclic, based on p-hydroxy-phenylglycine in the P2 position were prepared and their inhibitory effect determined. When the p-hydroxy group was replaced by methoxy, isoquinolin-, or quinolinyloxy functions, inhibitors with improved potencies were obtained. The P2 phenylglycine-based inhibitors were further optimized by C-terminal extension to acyl sulfonamides and by P1-P3 cyclization, which gave products with inhibition constants in the nanomolar range (similar to 75 nM). (c) 2006 Elsevier Ltd. All rights reserved.