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.
Rhoden
Jill B
JB
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA.
Bouvet
Maud
M
Izenwasser
Sari
S
Wade
Dean
D
Lomenzo
Stacey A
SA
Trudell
Mark L
ML
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