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) |
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Pages (from-to) | 5623-5634 |
Number of pages | 12 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 13 |
Issue number | 19 |
DOIs | |
State | Published - Oct 1 2005 |
Keywords
- Dopamine transporter
- Meperidine
- Serotonin transporter
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science