4-Aminopyridine derivatives with antiamnesic activity.
Acetylcholine (Ach) enhancement, useful in the treatment of Alzheimer's disease (AD), may be obtained by means of ion channel modulators such as 4-aminopyridine (4-AP). 4-AP is also the central ring of tacrine, the first drug approved for the treatment of AD. The synthesis and pharmacological activity of three 4-AP derivatives, prepared with the aim of improving their antiamnesic activity, is here described. In two of these compounds 4-AP is connected to 4-aminobutyric acid (GABA), whereas in the third it is connected to 2-indolinone, i.e., the skeleton of linopirdine, another Ach enhancing agent. The new compounds showed potent antiamnesic activity in comparison with piracetam.
Andreani
A
A
Dipartimento di Scienze Farmaceutiche, Universita' di Bologna, Via Belmeloro 6, 40126, Bologna, Italy. aldoandr@alma.unibo.it
Leoni
A
A
Locatelli
A
A
Morigi
R
R
Rambaldi
M
M
Pietra
C
C
Villetti
G
G
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000737:chemistry; D000544:Alzheimer Disease / Q000188:drug therapy; D000631:Aminopyridines / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001362:Avoidance Learning; D002245:Carbon Dioxide; D007211:Indoles / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D051379:Mice; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D010889:Piracetam / Q000627:therapeutic use
C409478:(3-(pyridin-4-ylcarbamoyl)propyl)carbamic acid tert-butyl ester; C409480:3-(4-aminopyridin-3-ylmethylene)-1,3-dihydroindol-2-one; C409479:4-amino-N-pyridin-4-ylbutyramide; D000631:Aminopyridines; D007211:Indoles; D018697:Nootropic Agents; D002245:Carbon Dioxide; D015761:4-Aminopyridine; D010889:Piracetam