A series of 6alpha- and 6beta-substituted benztropines were synthesized. A marked enantioselectivity was observed for the 6beta-methoxylated benztropines, the (1R)-isomers being more potent than the corresponding (1S) compounds. The racemic 6alpha-methoxy-3-(4',4' '-difluorodiphenylmethoxy)tropane (5 g) 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 6beta-methoxytropinone proved the 6R configuration for the (+)-enantiomer.

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

SIMONI, Daniele;ROSSI, Marcello;BERTOLASI, Valerio;RONDANIN, Riccardo;BARUCHELLO, Riccardo;MERIGHI, Stefania;VARANI, Katia;GESSI, Stefania;BOREA, Pier Andrea;MARINO, Silvia;CAVALLINI, Sabrina;BIANCHI, Clementina;SINISCALCHI, Anna
2005

Abstract

A series of 6alpha- and 6beta-substituted benztropines were synthesized. A marked enantioselectivity was observed for the 6beta-methoxylated benztropines, the (1R)-isomers being more potent than the corresponding (1S) compounds. The racemic 6alpha-methoxy-3-(4',4' '-difluorodiphenylmethoxy)tropane (5 g) 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 6beta-methoxytropinone proved the 6R configuration for the (+)-enantiomer.
Simoni, Daniele; Rossi, Marcello; Bertolasi, Valerio; Roberti, M; Pizzirani, D; Rondanin, Riccardo; Baruchello, Riccardo; Invidiata, Fp; Tolomeo, M; Grimaudo, S; Merighi, Stefania; Varani, Katia; Gessi, Stefania; Borea, Pier Andrea; Marino, Silvia; Cavallini, Sabrina; Bianchi, Clementina; Siniscalchi, Anna
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1198100
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