Design, synthesis and preliminary pharmacological evaluation of new piperidine and piperazine derivatives as cognition-enhancers.
A series of 2-oxopiperazine, 4-aminomethyl-, 3-amino- and 3-aminomethylpiperidine analogues of DM235 (sunifiram) and MN19 (sapunifiram), two previously reported potent cognition-enhancers, have been synthesized and tested in the mouse passive-avoidance test. The compounds display minimal effective doses in the range 0.3-10mg/kg. Although the new substances do not show improved activity when compared to the parent compounds, some useful information has been obtained to understand structure-activity relationships. In addition, the 3-aminopiperidine moiety appears to be a promising scaffold to synthesize new drugs endowed with cognition-enhancing activity.
Martini
Elisabetta
E
Laboratory of Design, Synthesis and Study of Biologically Active Heterocycles (HeteroBioLab), Department of Pharmaceutical Sciences, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
Ghelardini
Carla
C
Dei
Silvia
S
Guandalini
Luca
L
Manetti
Dina
D
Melchiorre
Michele
M
Norcini
Monica
M
Scapecchi
Serena
S
Teodori
Elisabetta
E
Romanelli
Maria Novella
MN
D000215:Acylation; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D015195:Drug Design; D051379:Mice; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry
D010880:Piperidines; C032727:piperidine; D013455:Sulfur