Structure-activity studies of 3'-4'-dichloro-meperidine analogues at dopamine and serotonin transporters.
The structure-activity relationships of 3',4'-dichloro-meperidine were investigated at dopamine (DAT) and serotonin transporters (SERT). Large ester substituents and lipophilic groups at the 4-position favored molecular recognition at the SERT. The benzyl ester of 3',4'-dichloro-meperidine exhibited high potency and high selectivity for the SERT (DAT/SERT=760). Chemical modification of the ester group and N-substitution generally led to compounds with decreased DAT affinity. Only small esters and alkyl groups were tolerated at the 4-position of the meperidine ring system by the DAT. Overall, the meperidine analogues were generally more selective for the SERT than for the DAT.
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA.
Jill B
JB
Rhoden
Maud
M
Bouvet
Sari
S
Izenwasser
Dean
D
Wade
Stacey A
SA
Lomenzo
Mark L
ML
Trudell
D001667:Binding, Competitive / Q000187:drug effects; D008614:Meperidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
C506452:3'-4'-dichloromeperidine; D008614:Meperidine