Structure-activity studies of 3′-4′-dichloro-meperidine analogues at dopamine and serotonin transporters

Jill B. Rhoden; Maud Bouvet; Sari Izenwasser; Dean Wade; Stacey A. Lomenzo; Mark L. Trudell

doi:10.1016/j.bmc.2005.05.025

Structure-activity studies of 3′-4′-dichloro-meperidine analogues at dopamine and serotonin transporters

Jill B. Rhoden, Maud Bouvet, Sari Izenwasser, Dean Wade, Stacey A. Lomenzo, Mark L. Trudell

Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Article

11 Scopus citations

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.

Original language	English (US)
Pages (from-to)	5623-5634
Number of pages	12
Journal	Bioorganic and Medicinal Chemistry
Volume	13
Issue number	19
DOIs	https://doi.org/10.1016/j.bmc.2005.05.025
State	Published - Oct 1 2005

Keywords

Dopamine transporter
Meperidine
Serotonin transporter

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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Rhoden, J. B., Bouvet, M., Izenwasser, S., Wade, D., Lomenzo, S. A., & Trudell, M. L. (2005). Structure-activity studies of 3′-4′-dichloro-meperidine analogues at dopamine and serotonin transporters. Bioorganic and Medicinal Chemistry, 13(19), 5623-5634. https://doi.org/10.1016/j.bmc.2005.05.025

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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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AU - Rhoden, Jill B.

AU - Bouvet, Maud

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AU - Wade, Dean

AU - Lomenzo, Stacey A.

AU - Trudell, Mark L.

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KW - Serotonin transporter

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