tert-butyl (1S)-(1-{[(benzenesulfonyl)amino]carbonyl}butyl)carbamate | 625122-55-6

• 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: tert-butyl (1S)-(1-{[(benzenesulfonyl)amino]carbonyl}butyl)carbamate
• 英文别名: tert-butyl (1S)-1-{[(phenylsulfonyl)amino]carbonyl}butylcarbamate；tert-butyl (S)-1-{[(phenylsulfonyl)amino]carbonyl}butylcarbamate；tert-butyl N-[(2S)-1-(benzenesulfonamido)-1-oxopentan-2-yl]carbamate
• CAS: 625122-55-6
• 化学式: C₁₆H₂₄N₂O₅S
• 分子量: 356.443
• InChiKey: XAPWJYYSXGBZKS-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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 (1S)-(1-{[(benzenesulfonyl)amino]carbonyl}butyl)carbamate 在 盐酸 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 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-[[(1S)-1-(benzenesulfonylcarbamoyl)butyl]amino]-1-[4-[(7-methoxy-2-phenyl-4-quinolyl)oxy]phenyl]-2-oxo-ethyl]carbamoyl]-2-methyl-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：

  N-tert-butoxycarbonyl-L-norvaline 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 生成 tert-butyl (1S)-(1-{[(benzenesulfonyl)amino]carbonyl}butyl)carbamate
  参考文献：
  名称：

  Exploration of acyl sulfonamides as carboxylic acid replacements in protease inhibitors of the hepatitis C virus full-length NS3

  摘要：

  The hepatitis C virus (HCV) NS3 protease has emerged as a promising anti-HCV drug target. Herein, we present an investigation of NS3 inhibitors comprising the acyl sulfonamide functionality. A series of tetra- and tripeptide based acyl sulfonamide inhibitors and their structure-activity relationships from both enzymatic and cell-based in vitro assays are presented. In summary, the acidity of the acyl sulfonamide functionality, the character of the P1 side chain, and the acyl sulfonamide substituent were found to be important for the inhibitory potencies. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.045

文献信息

• Acyl sulfonamides as potent protease inhibitors of the hepatitis C virus full-Length NS3 (Protease-Helicase/NTPase): A comparative study of different C-terminals
  作者：Anja Johansson、Anton Poliakov、Eva Åkerblom、Karin Wiklund、Gunnar Lindeberg、Susanne Winiwarter、U.Helena Danielson、Bertil Samuelsson、Anders Hallberg

  DOI：10.1016/s0968-0896(03)00179-2

  日期：2003.6

  (protease-helicase/NTPase) are reported: (i) inhibitors comprising electrophilic serine traps (pentafluoroethyl ketones, alpha-keto acids, and alpha-ketotetrazoles), (ii) product-based inhibitors comprising a C-terminal carboxylate group, and (iii) previously unexplored inhibitors comprising C-terminal carboxylic acid bioisosteres (tetrazoles and acyl sulfonamides). Bioisosteric replacement with the tetrazole

  报道了三种丙型肝炎病毒（HCV）全长NS3蛋白酶抑制剂（蛋白酶-解旋酶/ NTPase）的合成和抑制效能：（i）包含亲电丝氨酸陷阱的抑制剂（五氟乙基酮，α-酮酸和（ii）包含C末端羧酸酯基团的基于产物的抑制剂，以及（iii）先前未开发的包含C末端羧酸生物等排体（四唑和酰基磺酰胺）的抑制剂。用四唑基团进行生物立体置换可提供与相应羧酸盐同等效力的抑制剂，而用苯基酰基磺酰胺基取代可产生更有效的抑制剂。六肽抑制剂Suc-Asp-D-Glu-Leu-Ile-Cha-Nva-NHSO（2）Ph和Suc-Asp-D-Glu-Leu-Ile-Cha-ACPC-NHSO（2）Ph与K（i ）分别为13.6和3.8 nM，与具有C末端羧酸盐的相应抑制剂相比，其效价大约高20倍，并且与含有天然半胱氨酸Suc-Asp-D-Glu-Leu-Ile-Cha-Cys-OH（K（ i）= 28 nM）。酰基磺酰胺基团构成
• Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
  申请人：Cottrell M. Kevin

  公开号：US20070161789A1

  公开（公告）日：2007-07-12

  The present invention relates to compounds of formula I: or a pharmaceutically acceptable salt or mixtures thereof that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection and to processes for preparing the compounds. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

  本发明涉及式I的化合物：或其药学上可接受的盐或混合物，其抑制丝氨酸蛋白酶活性，特别是丝氨酸蛋白酶NS3-NS4A的活性。因此，它们通过干扰丙型肝炎病毒的生命周期而起作用，并且也可用作抗病毒剂。本发明还涉及包含这些化合物的组合物，无论是用于外体使用还是用于治疗患有HCV感染的患者的给药，以及制备这些化合物的过程。本发明还涉及通过给予本发明的化合物组成物来治疗患者的HCV感染的方法。本发明还涉及制备这些化合物的过程。
• Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents
  作者：Anna Lampa、Angelica E. Ehrenberg、Sofia S. Gustafsson、Aparna Vema、Eva Åkerblom、Gunnar Lindeberg、Anders Karlén、U. Helena Danielson、Anja Sandström

  DOI：10.1016/j.bmc.2010.05.027

  日期：2010.7

  Phenylglycine has proved to be a useful P2 residue in HCV NS3 protease inhibitors. A novel pi-pi-interaction between the phenylglycine and the catalytic H57 residue of the protease is postulated. We hypothesized that the introduction of a vinyl on the phenylglycine might strengthen this pi-pi-interaction. Thus, herein is presented the synthesis and inhibitory potency of a series of acyclic vinylated phenylglycine-based HCV NS3 protease inhibitors. Surprisingly, inhibitors based on both D-and L-phenylglycine were found to be effective inhibitors, with a slight preference for the D-epimers. Furthermore, prime-side alkenylic extension of the C-terminal acylsulfonamide group gave significantly improved inhibitors with potencies in the nanomolar range (similar to 35 nM), potencies which were retained on mutant variants of the protease. (C) 2010 Elsevier Ltd. All rights reserved.
• US7208600B2
  申请人：——

  公开号：US7208600B2

  公开（公告）日：2007-04-24
• US8039623B2
  申请人：——

  公开号：US8039623B2

  公开（公告）日：2011-10-18