公开(公告)号：US5192762A

公开(公告)日：1993-03-09

申请号：US745027

申请日：1991-08-14

Applicant: Nancy M. Gray ,  Patricia C. Contreras

Inventor： Nancy M. Gray ,  Patricia C. Contreras

IPC: A61K31/135 ,  A61K31/16 ,  A61K31/445 ,  A61K31/495 ,  A61K31/505

CPC classification number: A61K31/495 ,  A61K31/135 ,  A61K31/16 ,  A61K31/445 ,  A61K31/505

Abstract: Certain bridged tricyclic amine compounds are described as being therapeutically effective in treatment of CNS disorders resulting from neurotoxic damage or neurodegenerative diseases, particularly those CNS disorders resulting from ischemic events. Compounds of particular interest for use as neuroprotective agents are those of the formula ##STR1## wherein each of R.sup.1 and R.sup.2 is independently selected from hydrido, loweralkyl, benzyl and phenyl; wherein each of R.sup.1 through R.sup.7 is independently selected from hydrido, loweralkyl, hydroxy, benzyl, phenyl, loweralkoxy, phenoxy, benzyloxy, halo and haloloweralkyl; wherein R.sup.18 may be selected from hydrido, loweralkyl, cycloalkyl of five or six carbon atoms, cycloalkylalkyl of six or seven carbon atoms, phenyl, hydroxyloweralkyl, and heteroaryl selected from saturated or fully unsaturated heterocyclic rings containing five to seven ring members of which one or two ring members are nitrogen atom; wherein each X is independently one or more groups selected from hydrido, hydroxy, loweralkyl, benzyl, phenyl, loweralkoxy, phenoxy, haloloweralkyl, halo, and loweralkanoyl; and wherein each of R.sup.23 through R.sup.30 is independently selected from hydrido, lower alkyl, benzyl, phenyl and halo; wherein R.sup.18 together with one of R.sup.23, R.sup.24, R.sup.29 or R.sup.30 may form a fused heterocyclic ring containing five or six ring members; or a pharmaceutically-acceptable salt thereof.

Abstract translation: 描述了某些桥连三环胺化合物在治疗由神经毒性损伤或神经变性疾病，特别是由缺血事件引起的CNS障碍引起的CNS障碍中的治疗有效性。 用作神经保护剂的特别感兴趣的化合物是下式的化合物：其中R 1和R 2各自独立地选自氢，低级烷基，苄基和苯基; 其中R 1至R 7各自独立地选自氢，低级烷基，羟基，苄基，苯基，低级烷氧基，苯氧基，苄氧基，卤代和卤代低级烷基; 其中R 18可以选自氢或低级烷基，5或6个碳原子的环烷基，6或7个碳原子的环烷基烷基，苯基，羟基低级烷基和选自饱和或完全不饱和的含有5-7个环成员的杂环，其中一个或 两个环成员是氮原子; 其中每个X独立地是一个或多个选自氢，羟基，低级烷基，苄基，苯基，低级烷氧基，苯氧基，卤代低级烷基，卤素和低级烷酰基的基团。 并且其中R 23至R 30各自独立地选自氢，低级烷基，苄基，苯基和卤素; 其中R 18与R 23，R 24，R 29或R 30中的一个可以形成含有五个或六个环成员的稠合杂环; 或其药学上可接受的盐。