申请人:G. D. Searle & Co.
公开号:US05055468A1
公开(公告)日:1991-10-08
Certain bridged tricyclic amine compounds are described as being therapeutically effective in treatments 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 lower-alkanoyl; 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.
描述了某些桥接的三环胺化合物在治疗由神经毒性损伤或神经退行性疾病引起的中枢神经系统疾病方面具有治疗效果,特别是那些由缺血事件引起的中枢神经系统疾病。作为神经保护剂使用的特别感兴趣的化合物为具有以下结构的化合物:其中R.sup.1和R.sup.2中的每一个独立选择自氢化物、较低烷基、苄基和苯基;其中R.sup.1到R.sup.7中的每一个独立选择自氢化物、较低烷基、羟基、苄基、苯基、较低氧烷氧基、苯氧基、苄氧基、卤素和卤代较低烷基;其中R.sup.18可以选择自氢化物、较低烷基、五或六个碳原子的环烷基、六或七个碳原子的环烷基烷基、苯基、羟基较低烷基和由饱和或完全不饱和的含有五到七个环成员的杂环环选择的杂环芳基,其中一个或两个环成员是氮原子;其中每个X独立地选择自氢化物、羟基、较低烷基、苄基、苯基、较低氧烷氧基、苯氧基、卤代较低烷基、卤素和较低烷酰基的一个或多个基团;以及R.sup.23到R.sup.30中的每一个独立选择自氢化物、较低烷基、苄基、苯基和卤素;其中R.sup.18与R.sup.23、R.sup.24、R.sup.29或R.sup.30中的一个可以形成含有五个或六个环成员的融合杂环环;或其药用盐。