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.

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Gong PK, Blough BE, Brieaddy LE, Huang X, Kuhar MJ, Navarro HA, Carroll FI

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.

J Med Chem. 2007 Jul 26;50(15):3686-95. Epub 2007 Jun 30.

PubMed ID
17602602 [ View in PubMed
]
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).

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CocaineSodium-dependent dopamine transporterKi (nM)2727.422Details
CocaineSodium-dependent dopamine transporterEC 50 (nM)2677.422Details
CocaineSodium-dependent noradrenaline transporterKi (nM)8307.422Details
CocaineSodium-dependent noradrenaline transporterEC 50 (nM)3857.422Details
CocaineSodium-dependent serotonin transporterKi (nM)6017.422Details
CocaineSodium-dependent serotonin transporterEC 50 (nM)3187.422Details