Effects of two-carbon bridge region methoxylation of benztropine: discovery of novel chiral ligands for the dopamine transporter.
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.
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. smd@dns.unife.it
D
D
Simoni
M
M
Roberti
R
R
Rondanin
R
R
Baruchello
M
M
Rossi
F P
FP
Invidiata
S
S
Merighi
K
K
Varani
S
S
Gessi
P A
PA
Borea
S
S
Marino
S
S
Cavallini
C
C
Bianchi
A
A
Siniscalchi
D001590:Benztropine / Q000737:chemistry / Q000494:pharmacology*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008968:Molecular Conformation; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D018727:Muscarinic Antagonists; D009419:Nerve Tissue Proteins; D001590:Benztropine