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Structure-activity studies of 3'-4'-dichloro-meperidine analogues at dopamine and serotonin transporters
Jill B Rhoden1, Maud Bouvet, Sari Izenwasser
1Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA.
Abstract:
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.
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