6533b825fe1ef96bd1283203
RESEARCH PRODUCT
Effects of two-carbon bridge region methoxylation of benztropine: discovery of novel chiral ligands for the dopamine transporter
Daniele SimoniStefania GessiRiccardo RondaninRiccardo BaruchelloPier Andrea BoreaSabrina CavalliniMarinella RobertiStefania MerighiSilvia MarinoFrancesco Paolo InvidiataClementina BianchiAnna SiniscalchiKatia VaraniMarcello Rossisubject
StereochemistryClinical BiochemistryMolecular ConformationPharmaceutical ScienceNerve Tissue ProteinsMuscarinic AntagonistsLigandsBiochemistryChemical synthesisStructure-Activity RelationshipDopamineBenzatropineDrug DiscoverymedicineMolecular BiologyDopamine transporterBenztropineDopamine Plasma Membrane Transport ProteinsMembrane GlycoproteinsbiologyBicyclic moleculeChemistryOrganic ChemistryMembrane Transport ProteinsBiological activityBenztropinebiology.proteinMolecular MedicineEnantiomerCarrier Proteinsmedicine.drugdescription
6-Methoxylated and 8-oxygenated benztropines were prepared and evaluated for their DAT and SERT activity (binding and uptake inhibition). Methoxylation at the two-carbon bridge of benztropine produced a novel class of potent and selective DAT ligands. An interesting enantioselectivity was also observed for this new class of chiral benztropines. The inactivity of the 8-oxygenated analogues seems to point out that, unlike cocaine and its analogues, interactions of benztropine ligands with DAT may be strongly governed by the nitrogen atom.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2001-03-01 | Bioorganic & Medicinal Chemistry Letters |