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Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3beta-[4-methylphenyl and 4-chlorophenyl]-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2007 Jul 26; Vol. 50 (15), pp. 3686-95. Date of Electronic Publication: 2007 Jun 30. - Publication Year :
- 2007
-
Abstract
- Synthetic methods were developed for the synthesis of the 3beta-(4-substituted phenyl)-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes (4a-s). The compounds were evaluated for their monoamine transporter binding and monoamine uptake inhibition properties using both rat brain tissue and cloned transporter assays. In general, the compounds showed higher dopamine transporter (DAT) affinity relative to the serotonin and norepinephrine transporters (SERT and NET, respectively) and greater [3H]dopamine uptake inhibition potency relative to [3H]serotonin and [3H]norepinephrine uptake inhibition. Several compounds were DAT selective relative to the SERT and NET in the monoamine transporter binding assays. The most potent and selective analog in the functional monoamine uptake inhibition test was 3beta-(4-methylphenyl-2 beta-[5-(3-nitrophenyl)thiazol-2-yl]tropane (4p).
- Subjects :
- Adrenergic Uptake Inhibitors chemical synthesis
Adrenergic Uptake Inhibitors chemistry
Adrenergic Uptake Inhibitors pharmacology
Animals
Binding, Competitive
Cell Line
Corpus Striatum metabolism
Dopamine Uptake Inhibitors chemical synthesis
Dopamine Uptake Inhibitors chemistry
Dopamine Uptake Inhibitors pharmacology
Frontal Lobe metabolism
Humans
In Vitro Techniques
Male
Mesencephalon metabolism
Norepinephrine Plasma Membrane Transport Proteins metabolism
Radioligand Assay
Rats
Rats, Sprague-Dawley
Serotonin Plasma Membrane Transport Proteins metabolism
Selective Serotonin Reuptake Inhibitors chemical synthesis
Selective Serotonin Reuptake Inhibitors chemistry
Selective Serotonin Reuptake Inhibitors pharmacology
Structure-Activity Relationship
Thiazoles chemistry
Thiazoles pharmacology
Tropanes chemistry
Tropanes pharmacology
Dopamine Plasma Membrane Transport Proteins metabolism
Thiazoles chemical synthesis
Tropanes chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 50
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17602602
- Full Text :
- https://doi.org/10.1021/jm0703035