4-aminopyridine derivatives with antiamnesic activity

Acetylcholine (Ach) enhancement, useful in the treatment of Alzheimer's dis ease (AD), may be obtained by means of ion channel modulators such as 4-ami nopyridine (4-AP). 4-AP is also the central ring of tacrine, the first drug approved for the treatment of AD. The synthesis and pharmacological activi ty of three 4-AP derivatives, prepared with the aim of improving their anti amnesic activity, is here described. In two of these compounds 4-AP is conn ected to 4-aminobutyric acid (GABA), whereas in the third it is connected t o 2-indolinone, i.e., the skeleton of linopirdine, another Ach enhancing ag ent. The new compounds showed potent antiamnesic activity in comparison wit h piracetam. (C) 2000 Edition scientifiques et medicales Elsevier SAS.