Synthesis and monoamine uptake inhibition of conformationally constrained 2beta-carbomethoxy-3beta-phenyl tropanes.
A series of 2beta-carbomethoxy-3beta-phenyl tropanes with conformationally constrained nitrogen substituents were synthesized as potential selective dopamine transporter ligands. These novel compounds were examined for their monoamine uptake inhibition potency at the human dopamine transporter (hDAT), the human serotonin transporter (hSERT) and the human noradrenalin transporter (hNET), stably expressed in human embryonic kidney cells (HEK). A SAR-study was conducted to determine the contribution of extended, 4-fluorinated, conformationally constrained C4 chains at the tropane nitrogen to human monoamine transporter affinity and selectivity.
Riss
Patrick Johannes
PJ
Institute of Nuclear Chemistry, Johannes Gutenberg-University Mainz, Fritz Strassmann-Weg 2, 55128, Mainz, Germany. riss@uni-mainz.de
Hummerich
René
R
Schloss
Patrick
P
D015306:Biogenic Monoamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D015306:Biogenic Monoamines; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D014326:Tropanes