(2S)-2-{[(benzyloxy)carbonyl]amino}-4,4-difluorobutanoic acid | 467438-39-7

• 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: (2S)-2-{[(benzyloxy)carbonyl]amino}-4,4-difluorobutanoic acid
• 英文别名: (S)-2-[(benzyloxycarbonyl)amino]-4,4-difluorobutanoic acid；(2S)-4,4-difluoro-2-(phenylmethoxycarbonylamino)butanoic acid
• CAS: 467438-39-7
• 化学式: C₁₂H₁₃F₂NO₄
• 分子量: 273.236
• InChiKey: CISQNFRKUHRRSX-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-氯苯乙胺 、 (2S)-2-{[(benzyloxy)carbonyl]amino}-4,4-difluorobutanoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 benzyl (1S)-1-({[2-(2-chlorophenyl)ethyl]amino}carbonyl)-3,3-difluoropropyl-carbamate
  参考文献：
  名称：

  Phenethyl Amides as Novel Noncovalent Inhibitors of Hepatitis C Virus NS3/4A Protease:  Discovery, Initial SAR, and Molecular Modeling

  摘要：

  The discovery of novel, reversible and competitive tripeptide inhibitors of the Hepatitis C virus NS3/4A serine protease is described. These inhibitors are characterized by the presence of a C-terminal phenethyl amide group, which extends into the prime side of the enzyme. Initial SAR together with molecular modeling and data from site-directed mutagenesis suggest an interaction of the phenethyl amide group with Lys-136.

  DOI：

  10.1021/jm025594q
• 作为产物：
  描述：

  苯甲氧羰酰琥珀酰亚胺 、 (S)?-?2-氨基-4,4-二氟丁酸 在 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 (2S)-2-{[(benzyloxy)carbonyl]amino}-4,4-difluorobutanoic acid
  参考文献：
  名称：

  Phenethyl Amides as Novel Noncovalent Inhibitors of Hepatitis C Virus NS3/4A Protease:  Discovery, Initial SAR, and Molecular Modeling

  摘要：

  The discovery of novel, reversible and competitive tripeptide inhibitors of the Hepatitis C virus NS3/4A serine protease is described. These inhibitors are characterized by the presence of a C-terminal phenethyl amide group, which extends into the prime side of the enzyme. Initial SAR together with molecular modeling and data from site-directed mutagenesis suggest an interaction of the phenethyl amide group with Lys-136.

  DOI：

  10.1021/jm025594q

文献信息

• QUINOLINE-CARBOXAMIDE DERIVATIVES AS P2Y12 ANTAGONISTS
  申请人：Nazaré Marc

  公开号：US20100135999A1

  公开（公告）日：2010-06-03

  The present invention relates to compounds of the formula I, in which R 1 ; R 2 ; R 3 ; R 4 ; R 5 ; R 6 ; Z; A; B; E; X; Q; J; V; G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong anti-aggregating effect on platelets and thus an anti-thrombotic effect and are suitable e.g. for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible antagonists of the platelet ADP receptor P2Y12, and can in general be applied in conditions in which an undesired activation of the platelet ADP receptor P2Y12 is present or for the cure or prevention of which an inhibition of the platelet ADP receptor P2Y12 is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  本发明涉及公式I的化合物，其中R1; R2; R3; R4; R5; R6; Z; A; B; E; X; Q; J; V; G和M具有所述声明中指示的含义。公式I的化合物是有价值的药理活性化合物。它们对血小板具有强烈的抗聚集作用，从而具有抗血栓作用，适用于治疗和预防心血管疾病，如血栓栓塞病或再狭窄。它们是血小板ADP受体P2Y12的可逆拮抗剂，通常适用于存在不良激活血小板ADP受体P2Y12的情况，或者治愈或预防需要抑制血小板ADP受体P2Y12的情况。此外，本发明还涉及制备公式I化合物的方法，它们的用途，特别是作为药物中的活性成分，以及包含它们的制药制剂。
• Quinoline-carboxamide derivatives as P2Y12 antagonists
  申请人：Nazare Marc

  公开号：US08669266B2

  公开（公告）日：2014-03-11

  The present invention relates to compounds of the formula I, in which R1; R2; R3; R4; R5; R6; Z; A; B; E; X; Q; J; V; G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong anti-aggregating effect on platelets and thus an anti-thrombotic effect and are suitable e.g. for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible antagonists of the platelet ADP receptor P2Y12, and can in general be applied in conditions in which an undesired activation of the platelet ADP receptor P2Y12 is present or for the cure or prevention of which an inhibition of the platelet ADP receptor P2Y12 is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  本发明涉及公式I的化合物，其中R1; R2; R3; R4; R5; R6; Z; A; B; E; X; Q; J; V; G和M具有所述权利要求中指定的含义。公式I的化合物是有价值的药理活性化合物。它们在血小板上表现出强烈的抗聚集作用，因此具有抗血栓作用，适用于治疗和预防心血管疾病，如血栓栓塞病或再狭窄。它们是血小板ADP受体P2Y12的可逆拮抗剂，并且通常可以应用于存在不希望的血小板ADP受体P2Y12激活或需要抑制血小板ADP受体P2Y12的治疗或预防的情况。此外，本发明还涉及公式I的化合物的制备方法，它们的使用，特别是作为药物的活性成分，以及包含它们的药物制剂。
• 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.
• SAR and pharmacokinetic studies on phenethylamide inhibitors of the hepatitis C virus NS3/NS4A serine protease
  作者：Savina Malancona、Stefania Colarusso、Jesus M Ontoria、Antonella Marchetti、Marco Poma、Ian Stansfield、Ralph Laufer、Annalise Di Marco、Marina Taliani、Maria Verdirame、Odalys Gonzalez-Paz、Victor G Matassa、Frank Narjes

  DOI：10.1016/j.bmcl.2004.05.093

  日期：2004.9

  SAR on the phenethylamide I (K-i 1.2 muM) in the P2- and the V-position led to potent inhibitors, one of which showed good exposure and low clearance when administered intramuscularly to rat. (C) 2004 Elsevier Ltd. All rights reserved.
• US8669266B2
  申请人：——

  公开号：US8669266B2

  公开（公告）日：2014-03-11