Boc-D-Val-N-MeArg(Tos)-Gly-OBzl | 153346-65-7

• 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: Boc-D-Val-N-MeArg(Tos)-Gly-OBzl
• 英文别名: Boc-D-Val-NMeArg(Tos)-Gly-OBzl；benzyl 2-[[(2S)-5-[[amino-[(4-methylphenyl)sulfonylamino]methylidene]amino]-2-[methyl-[(2R)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]pentanoyl]amino]acetate
• CAS: 153346-65-7
• 化学式: C₃₃H₄₈N₆O₈S
• 分子量: 688.846
• InChiKey: SWZFPOFYMOZYGZ-XTEPFMGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  48
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  207
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Boc-D-Val-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 6.75h， 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：

  Boc-N-MeArg(Tos)-Gly-OBzl 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， 反应 0.33h， 生成 Boc-D-Val-N-MeArg(Tos)-Gly-OBzl
  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

文献信息

• Radiolabeled platelet GPIIb/IIIa receptor antagonists as imaging agents
  申请人：DuPont Pharmaceuticals Company

  公开号：US06022523A1

  公开（公告）日：2000-02-08

  This invention provides novel radiopharmaceuticals that are radiolabeled cyclic compounds containing carbocyclic or heterocyclic ring systems which act as antagonists of the platelet glycoprotein IIb/IIIa complex; to methods of using said radiopharmaceuticals as imaging agents for the diagnosis of arterial and venous thrombi; to novel reagents for the preparation of said radiopharmaceuticals; and to kits comprising said reagents.

  本发明提供了新型放射性药物，它们是放射性标记的环状化合物，包含碳环或杂环环系统，可作为血小板糖蛋白IIb/IIIa复合物的拮抗剂；本发明还提供了使用该放射性药物作为诊断动脉和静脉血栓的成像剂的方法；提供了制备该放射性药物的新型试剂；以及包含该试剂的试剂盒。