公开(公告)号：US20050239808A1

公开(公告)日：2005-10-27

申请号：US10514015

申请日：2003-05-09

申请人： Thomas Schrader ,  Detlev Riesner ,  Petra Rzepecki ,  Luitgard Nagel-Steger ,  Mark Wehner ,  Christian Kirsten ,  Oliver Molt ,  Reza Zadmard ,  Katja Aschermann

发明人： Thomas Schrader ,  Detlev Riesner ,  Petra Rzepecki ,  Luitgard Nagel-Steger ,  Mark Wehner ,  Christian Kirsten ,  Oliver Molt ,  Reza Zadmard ,  Katja Aschermann

IPC分类号： A61P25/28 ,  C07D231/40 ,  C07D401/14 ,  A61K31/522 ,  A61K31/416 ,  A61K31/4196 ,  A61K31/4709 ,  C07D473/02 ,  C07D43/02

CPC分类号： C07D231/40 ,  C07D401/14

摘要： The invention on hand refers to diseases associated with abnormal protein structures, including Alzheimer's disease, Creutzfeldt-Jakob's disease, BSE and other prion-associated diseases. It is the task of the invention on hand to provide new active agents preventing the formation of amyloid plaques and to dissolve existing plaques, such agents being convenient for therapy, diagnosis and prophylaxis of diseases that are associated with abnormal protein structures. This task is performed in terms of the current invention by heterocyclic or aromatic agents with a rigid structure and a donor-acceptor-donor pattern (DAD), the latter being formed by donors and acceptors of hydrogen bridge linkages which comply with the β-sheet structure of the peptide or protein and thus fit as binding partners. The heterocyclic or aromatic agents are available at least as dimers. They recognise peptides and proteins with a β-sheet structure, form stable complexes with them and inhibit their aggregation to β-amyloid plaques. Furthermore, the new active agents are able to dissolve β-amyloid plaques that already exist. Another task of the current invention is to provide methods for the synthesis of said heterocyclic or aromatic compounds.

摘要翻译： 手头的发明是指与异常蛋白质结构相关的疾病，包括阿尔茨海默病，克雅氏病，疯牛病和其他朊病毒相关疾病。 本发明的任务是提供防止淀粉样蛋白斑块形成和溶解现有斑块的新的活性剂，所述药剂便于治疗，诊断和预防与异常蛋白质结构相关的疾病。 根据本发明，通过具有刚性结构和供体 - 受体 - 给体模式（DAD）的杂环或芳族化合物来执行该任务，后者由供体和符合β-折叠板的氢桥连接体的受体形成 肽或蛋白质的结构，因此适合作为结合配偶体。 杂环或芳族试剂至少可以作为二聚体获得。 它们识别具有β-折叠结构的肽和蛋白质，与它们形成稳定的复合物并抑制它们与β-淀粉样蛋白斑的聚集。 此外，新的活性剂能够溶解已经存在的β-淀粉样斑块。 本发明的另一个任务是提供合成所述杂环或芳族化合物的方法。