Skip to Content

QSAR study and synthesis of new phenyltropanes as ligands of the dopamine transporter (DAT).

QSAR study and synthesis of new phenyltropanes as ligands of the dopamine transporter (DAT).

Bioorganic & medicinal chemistry (2012-02-04)

Sylvie Mavel, Zoya Mincheva, Nathalie Méheux, Yvan Carcenac, Denis Guilloteau, Mohamed Abarbri, Patrick Emond

ABSTRACT

The dopamine transporter (DAT) plays a pivotal role in the regulation of dopamine neurotransmission, and is involved in a number of physiological functions and brain disorders. Furthermore the DAT analysis by molecular imaging techniques is a useful tool for the diagnosis and follow up treatment of diseases involving the DAT. In order to predict the affinity of new derivatives for the DAT, different QSAR molecular modeling models based on cocaine were compared. We have evaluated in these models tropane derivatives synthesized with original synthons which coupled properties of both fluorine and iodine atoms. One compound showed a high in vitro affinity and selectivity for the DAT (K(i)=0.87±0.04 nM). This compound should be radiolabeled with radioiodine for further investigations by SPECT.

MATERIALS

Product Number

Brand

Product Description

Supelco

Naphthalene solution, certified reference material, 5000 μg/mL in methanol

Sigma-Aldrich

Bromobenzene, ReagentPlus^®, 99%

Sigma-Aldrich

Bromobenzene, ≥99.5% (GC)

Sigma-Aldrich

Naphthalene, 99%

Supelco

Naphthalene, analytical standard

Sigma-Aldrich

Naphthalene, suitable for scintillation, ≥99%

Sigma-Aldrich

Aniline, ReagentPlus^®, 99%

Sigma-Aldrich

Aniline, ACS reagent, ≥99.5%

Supelco

Aniline, analytical standard

Supelco

Naphthalene, certified reference material, TraceCERT^®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland

Sigma-Aldrich

Phenol, for molecular biology

Sigma-Aldrich

Liquified Phenol, ≥89.0%

Sigma-Aldrich

Phenol solution, BioReagent, Equilibrated with 10 mM Tris HCl, pH 8.0, 1 mM EDTA, for molecular biology

Sigma-Aldrich

Phenol, BioXtra, ≥99.5% (GC)

Sigma-Aldrich

Phenol solution, BioReagent, Saturated with 0.01 M citrate buffer, pH 4.3 ± 0.2, for molecular biology

Sigma-Aldrich

2-Naphthol, BioXtra, ≥99.0% (GC)

Sigma-Aldrich

Phenol, BioUltra, for molecular biology, TE-saturated, ~73% (T)

Supelco

Phenol solution, 100 μg/mL in acetonitrile, PESTANAL^®, analytical standard

Sigma-Aldrich

Pyridine, ≥99%

Sigma-Aldrich

Benzyl chloride, ReagentPlus^®, 99%, contains ≤1% propylene oxide as stabilizer

Sigma-Aldrich

Biphenyl, ≥99%

Sigma-Aldrich

Phenol, ≥99%

Sigma-Aldrich

Phenol, BioUltra, for molecular biology, ≥99.5% (GC)

Supelco

Hexachlorobenzene, PESTANAL^®, analytical standard

Sigma-Aldrich

Phenol, puriss., meets analytical specification of Ph. Eur., BP, USP, 99.5-100.5% (GC)

Supelco

Phenol solution, certified reference material, 500 μg/mL in methanol

Supelco

Phenol solution, 5000 μg/mL in methanol, certified reference material

Sigma-Aldrich

Biphenyl, ReagentPlus^®, 99.5%

Supelco

Biphenyl, PESTANAL^®, analytical standard

Supelco

Toluene, analytical standard