Synthesis and structure-activity relationships of novel arylalkyl 4-benzyl piperazine derivatives as sigma site selective ligands.
Continuing our previous work that established that some chromones substituted by an aryl alkyl piperazino alkyl side chain are potent and selective sigma ligands and could be interesting in the treatment of psychosis, we synthesized 60 new compounds, replacing the chromone moiety by various cyclic systems. Many derivatives bind to the sigma sites in the nanomolar range and are generally selective in comparison with 5HT(1A) and the D(2) receptors. One of the most potent ligands of these series, 1-(2-naphthyl methyl)-4-benzyl piperazine 29, has been studied in various pharmacological tests. Although it doesn't have potential in the treatment of psychosis, the results we obtained confirm the data which indicates that such derivatives could be interesting in the treatment of inflammatory diseases.
Younes
S
S
Laboratoire de chimie pharmaceutique, faculté de pharmacie, 35, chemin des Maraîchers, 31062, Toulouse, France.
Labssita
Y
Y
Baziard-Mouysset
G
G
Payard
M
M
Rettori
M
M
Renard
P
P
Pfeiffer
B
B
Caignard
D
D
D000818:Animals; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D016202:N-Methylaspartate / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000378:metabolism*; D013329:Structure-Activity Relationship
C409484:1-(2-naphthylmethyl)-4-benzylpiperazine; D010879:Piperazines; D017480:Receptors, sigma; D016202:N-Methylaspartate; D002351:Carrageenan; D009638:Norepinephrine