methyl 8-(aminomethyl)-2-naphthoate | 153346-59-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 8-(aminomethyl)-2-naphthoate
• 英文别名: methyl 8-aminomethyl-5,6,7,8-tetrahydro-2-naphthoate；Methyl 8-aminomethyl-2-naphthoate；methyl 8-(aminomethyl)naphthalene-2-carboxylate
• CAS: 153346-59-9
• 化学式: C₁₃H₁₃NO₂
• 分子量: 215.252
• InChiKey: LRFDYFNVLLNJDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 8-(aminomethyl)-2-naphthoate 在 lithium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 45.0h， 生成 N-(tert-butyloxycarbonyl)-8-(aminomethyl)-2-naphthoic acid
  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：

  methyl 8-cyano-2-naphthoate 在 钯 盐酸 作用下， 以 甲醇 为溶剂， 生成 methyl 8-(aminomethyl)-2-naphthoate
  参考文献：
  名称：

  Radiolabeled platelet GPIIb/IIIa receptor antagonists as imaging agents

  摘要：

  这项发明提供了新型放射性药物，这些药物是含有碳环或杂环环系统的放射性标记的环化合物，其作为血小板糖蛋白IIb/IIIa复合物的拮抗剂；用于将所述放射性药物作为影像剂用于诊断动脉和静脉血栓的方法；用于制备所述放射性药物的新型试剂；以及包含所述试剂的试剂盒。

  公开号：

  US05879657A1

文献信息

• Cyclic compounds useful as inhibitors of platelet glycoprotein IIB/IIIA
  申请人：The DuPont Merck Pharmaceutical Company

  公开号：US05635477A1

  公开（公告）日：1997-06-03

  This invention relates to novel cyclic compounds containing carbocyclic ring systems useful as antagonists of the platelet glycoprotein IIb/IIIa complex, to pharmaceutical compositions containing such cyclic compounds, with or without other therapeutic agents, and to methods of using these compounds, with or without other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of other thromboembolic disorders. This invention also relates to methods of using the cyclic compounds of the invention in combination with anti-coagulants such as warfarin or heparin, or additional anti-platelet agents such as aspirin, piroxicam or ticlopidine, or thrombin inhibitors such as boropeptides, hirudin or argatroban, or thrombolytic agents such as tissue plasminogen activator, anistreplase, urokinase or streptokinase, or combinations thereof, for the treatment of thromboembolic disorders. A representative compound of the invention is cyclo(D-Val-(.sup..alpha. N-methyl Arg)-Gly-Asp-(3-aminomethylbenzoic acid).

  本发明涉及新型含环状化合物的抗血小板糖蛋白IIb/IIIa复合物拮抗剂，这些化合物含有碳环状系统，可用于制备药物组合物，包括这些环状化合物，与或不含其他治疗剂，以及使用这些化合物，与或不含其他治疗剂，用于抑制血小板聚集，作为溶栓剂和/或用于治疗其他血栓栓塞性疾病的方法。本发明还涉及使用本发明的环状化合物与抗凝剂（如华法林或肝素）或其他抗血小板剂（如阿司匹林、吡罗昔康或替克洛匹定）或凝血酶抑制剂（如硼肽、酶素或阿加曲班）或溶栓剂（如组织型纤溶酶原激活剂、安斯特雷普拉斯、尿激酶或链激酶）或其组合物，用于治疗血栓栓塞性疾病的方法。本发明的代表性化合物是环状D-Val-(.sup..alpha. N-甲基Arg)-Gly-Asp-(3-氨甲基苯甲酸)。
• Radiolabeled platelet GPIIb/IIIa receptor antagonists as imaging agents for the diagnosis of thromboembolic disorders
  申请人：Dupont Pharmaceuticals Company

  公开号：EP0995761A2

  公开（公告）日：2000-04-26

  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 the 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，它们是含有碳环或杂环环系统的放射性标记环状化合物，可作为血小板糖蛋白 IIb/IIIa 复合物的拮抗剂；提供了将所述放射性药物用作诊断动脉和静脉血栓的成像剂的方法；提供了制备所述放射性药物的新型试剂；以及提供了包含所述试剂的试剂盒。
• ERNEST, I.;VUILLEUMIER, S.;FRITZ, H.;MUTTER, M., TETRAHEDRON LETT., 31,(1990) N8, C. 4015-4018
  作者：ERNEST, I.、VUILLEUMIER, S.、FRITZ, H.、MUTTER, M.

  DOI：——

  日期：——
• ERNEST, I.;KALVODA, J.;RIHS, G.;MUTTER, M., TETRAHEDRON LETT., 31,(1990) N8, C. 4011-4014
  作者：ERNEST, I.、KALVODA, J.、RIHS, G.、MUTTER, M.

  DOI：——

  日期：——
• CYCLIC COMPOUNDS USEFUL AS INHIBITORS OF PLATELET GLYCOPROTEIN IIb/IIIa
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：EP0625164A1

  公开（公告）日：1994-11-23