A series of 6α- and 6β-substituted benztropines were synthesized. A marked enantioselectivity was observed for the 6β-methoxylated benztropines, the (1R)-isomers being more potent than the corresponding (1S) compounds. The racemic 6α-methoxy-3-(4′,4″- difluorodiphenylmethoxy)-tropane (5g) was the most potent compound. It has been found that modifications at the 6-position of benztropine might reduce the DAT binding affinity, maintaining otherwise a significant dopamine uptake inhibitory activity. A reinvestigation of the absolute configuration of 6β-methoxytropinone proved the 6R configuration for the (+)-enantiomer.

SIMONI D, ROSSI M, BERTOLASI V, ROBERTI M, PIZZIRANI D, RONDANIN R, et al. (2005). Synthesis and pharmacology of 6-substituted benztropines: discovery of novel dopamine uptake inhibitors possessing low binding affinity to the dopamine transporter. JOURNAL OF MEDICINAL CHEMISTRY, 48(9), 3337-3343 [10.1021/jm0490235].

Synthesis and pharmacology of 6-substituted benztropines: discovery of novel dopamine uptake inhibitors possessing low binding affinity to the dopamine transporter

Rossi, Matteo;INVIDIATA, Francesco;GRIMAUDO, Stefania;
2005-01-01

Abstract

A series of 6α- and 6β-substituted benztropines were synthesized. A marked enantioselectivity was observed for the 6β-methoxylated benztropines, the (1R)-isomers being more potent than the corresponding (1S) compounds. The racemic 6α-methoxy-3-(4′,4″- difluorodiphenylmethoxy)-tropane (5g) was the most potent compound. It has been found that modifications at the 6-position of benztropine might reduce the DAT binding affinity, maintaining otherwise a significant dopamine uptake inhibitory activity. A reinvestigation of the absolute configuration of 6β-methoxytropinone proved the 6R configuration for the (+)-enantiomer.
SIMONI D, ROSSI M, BERTOLASI V, ROBERTI M, PIZZIRANI D, RONDANIN R, et al. (2005). Synthesis and pharmacology of 6-substituted benztropines: discovery of novel dopamine uptake inhibitors possessing low binding affinity to the dopamine transporter. JOURNAL OF MEDICINAL CHEMISTRY, 48(9), 3337-3343 [10.1021/jm0490235].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/14975
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