Structure-activity studies of 3'-4'-dichloro-meperidine analogues at dopamine and serotonin transporters.
Bioorganic & medicinal chemistry 2005 Oct 1; 13(19):5623-34
Rhoden J JB, Bouvet M M, Izenwasser S S, Wade D D, Lomenzo S SA, Trudell M ML
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA.
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.