Effects of two-carbon bridge region methoxylation of benztropine: discovery of novel chiral ligands for the dopamine transporter.

Dipartimento di Scienze Farmaceutiche, Universita di Ferrara, Italy. smd@dns.unife.it
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.
Mesh Terms:
Benztropine, Carrier Proteins, Dopamine Plasma Membrane Transport Proteins, Ligands, Membrane Glycoproteins, Membrane Transport Proteins, Molecular Conformation, Muscarinic Antagonists, Nerve Tissue Proteins, Structure-Activity Relationship
Bioorg. Med. Chem. Lett. Mar. 26, 2001; 11(6);823-7 [PUBMED:11277529]
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