N-MeArg(Tos)-Gly-OBzl | 144838-92-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-MeArg(Tos)-Gly-OBzl
• 英文别名: benzyl 2-[[(2S)-5-[[amino-[(4-methylphenyl)sulfonylamino]methylidene]amino]-2-(methylamino)pentanoyl]amino]acetate
• CAS: 144838-92-6
• 化学式: C₂₃H₃₁N₅O₅S
• 分子量: 489.596
• InChiKey: JWHORKFTNMOEGS-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  34
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-MeArg(Tos)-Gly-OBzl 在 palladium on activated charcoal 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 cyclohexyl 2-((5S,11S,14R)-14-isopropyl-2,12-dimethyl-4,7,10,13,16-pentaoxo-11-(3-(3-tosylguanidino)propyl)-3,6,9,12,15-pentaaza-1(1,3)-benzenacyclohexadecaphane-5-yl)acetate
  参考文献：
  名称：

  Template-Constrained Cyclic Peptides: Design of High-Affinity Ligands for GPIIb/IIIa

  摘要：

  Although peptides adopt a large ensemble of conformations in aqueous solution, they are generally believed to bind to a receptor in a unique conformation. Thus, there is considerable interest in devising methods to restrict the conformational freedom of peptides. One such approach involves tying the amino and carboxy terminal ends of the peptide onto a semirigid template that will lock the intervening peptide backbone into a single conformer or a family of related conformers. This general strategy has been tested using the tripeptide sequence Arg-Gly-Asp (RGD), which binds with low affinity to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa or alpha(IIb)beta(3)) Mimics of RGD are of interest as antithrombotics because of their ability to inhibit the aggregation of platelets. Prior to this study, other workers (Samanen et al. J. Med. Chem. 1991, 34, 3114-3125) prepared a disulfide-containing cyclic pentapeptide that bound to GPIIb/IIIa with an affinity of approximately 0.1 mu M. NMR analysis of the solution conformation of this peptide suggested that replacing the disulfide-containing portion of the cycle with the amino acid m-(aminomethyl)benzoic acid would lead to a more rigid structure. Indeed, introduction of this template into a cyclic ROD-containing peptide resulted in compounds with high affinity for the receptor. Further, systematic inclusion of additional conformational constraints in the form of N-alpha- and C-alpha-alkyl groups led to a peptide with an affinity of approximately 100 pM for binding to the receptor. This peptide also showed good activity in the platelet aggregation assay at oral doses as low as 0.1 mg/kg.

  DOI：

  10.1021/ja00087a007
• 作为产物：
  描述：

  甘氨酸苄酯盐酸盐 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-MeArg(Tos)-Gly-OBzl
  参考文献：
  名称：

  Tc-99m-labeled fibrinogen receptor antagonists: design and synthesis of cyclic RGD peptides for the detection of thrombi

  摘要：

  Tc-99m labeled derivatives of N-Me-Arg-Gly-Asp containing cyclic peptide GP IIb/IIIa receptor antagonists are potential radiopharmaceuticals for the diagnosis of thrombosis. The design and synthesis of these peptides are described. These compounds are incorporated in rapidly growing thrombi under both arterial and venous conditions in canine models. Thrombi are clearly visible in images acquired at 50 min. Copyright (C) 1996 The DuPont Merck Pharmaceutical Company.

  DOI：

  10.1016/0960-894x(96)00282-x

文献信息

• Facile detosylation of cyclic peptides. An effective synthesis of platelet glycoprotein IIb/IIIa inhibitors
  作者：Lin-hua Zhang、Philip Ma

  DOI：10.1016/s0040-4039(00)78178-0

  日期：1994.8

  A general and effective synthesis of cyclic pentapeptides containing Arg-Gly-Asp sequence, which are potent antithrombotic agents, is reported.
• An Efficient Synthesis of Cyclic RGD Peptides as Antithrombotic Agents
  作者：Lin-hua Zhang、J. A. Pesti、T. D. Costello、P. J. Sheeran、R. Uyeda、P. Ma、G. S. Kauffman、R. Ward、J. L. McMillan

  DOI：10.1021/jo9603284

  日期：1996.1.1
• Template-Constrained Cyclic Peptides: Design of High-Affinity Ligands for GPIIb/IIIa
  作者：Sharon Jackson、W. DeGrado、A. Dwivedi、A. Parthasarathy、A. Higley、J. Krywko、A. Rockwell、J. Markwalder、G. Wells

  DOI：10.1021/ja00087a007

  日期：1994.4

  Although peptides adopt a large ensemble of conformations in aqueous solution, they are generally believed to bind to a receptor in a unique conformation. Thus, there is considerable interest in devising methods to restrict the conformational freedom of peptides. One such approach involves tying the amino and carboxy terminal ends of the peptide onto a semirigid template that will lock the intervening peptide backbone into a single conformer or a family of related conformers. This general strategy has been tested using the tripeptide sequence Arg-Gly-Asp (RGD), which binds with low affinity to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa or alpha(IIb)beta(3)) Mimics of RGD are of interest as antithrombotics because of their ability to inhibit the aggregation of platelets. Prior to this study, other workers (Samanen et al. J. Med. Chem. 1991, 34, 3114-3125) prepared a disulfide-containing cyclic pentapeptide that bound to GPIIb/IIIa with an affinity of approximately 0.1 mu M. NMR analysis of the solution conformation of this peptide suggested that replacing the disulfide-containing portion of the cycle with the amino acid m-(aminomethyl)benzoic acid would lead to a more rigid structure. Indeed, introduction of this template into a cyclic ROD-containing peptide resulted in compounds with high affinity for the receptor. Further, systematic inclusion of additional conformational constraints in the form of N-alpha- and C-alpha-alkyl groups led to a peptide with an affinity of approximately 100 pM for binding to the receptor. This peptide also showed good activity in the platelet aggregation assay at oral doses as low as 0.1 mg/kg.
• Tc-99m-labeled fibrinogen receptor antagonists: design and synthesis of cyclic RGD peptides for the detection of thrombi
  作者：Thomas D. Harris、Milind Rajopadhye、Paul R. Damphousse、Danuta Glowacka、Karmine Yu、Jeffrey P. Bourque、John A. Barrett、David J. Damphousse、Stuart J. Heminway、Joel Lazewatsky、Theresa Mazaika、Timothy R. Carroll

  DOI：10.1016/0960-894x(96)00282-x

  日期：1996.8

  Tc-99m labeled derivatives of N-Me-Arg-Gly-Asp containing cyclic peptide GP IIb/IIIa receptor antagonists are potential radiopharmaceuticals for the diagnosis of thrombosis. The design and synthesis of these peptides are described. These compounds are incorporated in rapidly growing thrombi under both arterial and venous conditions in canine models. Thrombi are clearly visible in images acquired at 50 min. Copyright (C) 1996 The DuPont Merck Pharmaceutical Company.