公开(公告)号：US07704987B1

公开(公告)日：2010-04-27

申请号：US10031478

申请日：2000-07-21

申请人： Kevin Jeffrey Barnham ,  Thomas David McCarthy ,  Susanne Pallich ,  Barry Ross Matthews ,  Robert Alan Cherny

发明人： Kevin Jeffrey Barnham ,  Thomas David McCarthy ,  Susanne Pallich ,  Barry Ross Matthews ,  Robert Alan Cherny

IPC分类号： A61K31/555 ,  A61K31/4745 ,  C07D471/14

CPC分类号： C07K14/4711 ,  A61K38/00 ,  A61K47/54 ,  A61K47/547

摘要： The present invention relates to compounds which inhibit the binding of metal ions to a region in the N-terminal loop of the β-amyloid peptide which includes a cluster of histidine residues. In addition, the invention relates to pharmaceutical compositions including these compounds as the active agent, and to methods of treatment involving the administration of these compounds. The compounds of the invention are useful in the treatment of Alzheimer's Disease and other amyloid-related conditions. In a first aspect the present invention provides a compound which interacts with the β-amyloid peptide in such a way that the N-terminal loop of the peptide (amino acid residues 1-15) is blocked or destabilised, thereby inhibiting the binding of one or more metal ions to at least one histidine residue within the N-terminal loop. Preferably the compound inhibits binding of Cu2+, Zn2+ and Fe3+ ions, but not Mg2+ or Ca2+ ions.

摘要翻译： 本发明涉及抑制金属离子与包含一组组氨酸残基的β-淀粉状蛋白肽的N-末端环区域的结合的化合物。 此外，本发明涉及包含这些化合物作为活性剂的药物组合物以及涉及施用这些化合物的治疗方法。 本发明的化合物可用于治疗阿尔茨海默病和其他淀粉样蛋白相关病症。 在第一方面，本发明提供了一种与β-淀粉样蛋白肽相互作用的化合物，使得肽（氨基酸残基1-15）的N-末端环被阻断或不稳定，从而抑制 一个或多个金属离子至N末端环内的至少一个组氨酸残基。 优选地，化合物抑制Cu 2+，Zn 2+和Fe 3+离子而不是Mg 2+或Ca 2+离子的结合。