N-[(2S)-2-aminopentanoyl]benzenesulfonamide | 625122-59-0

• 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: N-[(2S)-2-aminopentanoyl]benzenesulfonamide
• 英文别名: (2S)-2-amino-N-(phenylsulphonyl)pentanamide；(2S)-2-amino-N-(benzenesulfonyl)pentanamide
• CAS: 625122-59-0
• 化学式: C₁₁H₁₆N₂O₃S
• 分子量: 256.326
• InChiKey: VHQGZMDAVVHTHC-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[(2S)-2-aminopentanoyl]benzenesulfonamide 在 盐酸 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成
  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：

  Carbamic acid, [(1S)-1-[[(phenylsulfonyl)amino]carbonyl]butyl]-,phenylmethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以100%的产率得到N-[(2S)-2-aminopentanoyl]benzenesulfonamide
  参考文献：
  名称：

  [EN] HCV NS-3 SERINE PROTEASE INHIBITORS
  [FR] INHIBITEURS DE LA NS-3 SERINE PROTEASE DU VHC

  摘要：

  公开号：

  WO2005073195A3

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
• HCV NS-3 Serine Protease Inhibitors
  申请人：Rosenquist Asa

  公开号：US20100003216A1

  公开（公告）日：2010-01-07

  Compounds of the formula where the variables are as defined in the specification inhibit the NS3 protease of flavivirus sych as hepatitis C virus (HCV). The compounds comprise a novel linkage between a heterocyclic P2 unit and those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

  式中的变量如规范中所定义，可以抑制黄热病病毒(NS3蛋白酶)等黄病毒的蛋白酶，如丙型肝炎病毒(HCV)。这些化合物包括一个新的链接，连接一个杂环P2单位和那些离原生底物的名义剪切位点更远的抑制剂部位，该链接将离剪切位点远侧的肽键的方向与靠近剪切位点的肽键的方向相反。
• Hcv ns-3 serine protease inhibitors
  申请人：Rosenquist Asa

  公开号：US20070161574A1

  公开（公告）日：2007-07-12

  Compounds of the formula where the variables are as defined in the specification inhibit the NS3 protease of flavivirus such as hepatitis C virus (HCV). The compounds comprise a novel linkage between a heterocyclic P2 unit and those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

  式子中的变量如规范所定义，能够抑制类黄病毒的NS3蛋白酶，例如丙型肝炎病毒（HCV）。这些化合物包括一种新颖的连接方式，连接了一个杂环P2单元和抑制剂更远离天然底物裂解位点的部分，该连接方式反转了远离裂解位点的肽键方向相对于靠近裂解位点的肽键方向。
• 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。
• Hcv Ns-3 Serine Protease Inhibitors
  申请人：Rosenquist Asa

  公开号：US20070203072A1

  公开（公告）日：2007-08-30

  Peptidomimetic compounds are described which inhibit the NS3 protease of the hepatitis C virus (HCV). The compounds have the formula where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

  本文描述了一种抑制丙型肝炎病毒（HCV）的NS3蛋白酶的肽类类似物化合物。该化合物的化学式中，变量定义如规范中所提供。该化合物包括一个碳环P2单元，与抑制剂更远离天然底物的名义剪切位点的那些部分的新型连接结合，该连接将远侧的肽键方向相对于靠近剪切位点的肽键反转。