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.
|Data di pubblicazione:||2005|
|Titolo:||Synthesis and pharmacology of 6-substituted benztropines: discovery of novel dopamine uptake inhibitors possessing low binding affinity to the dopamine transporter|
|Citazione:||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.|
|Digital Object Identifier (DOI):||10.1021/jm0490235|
|Appare nelle tipologie:||1.01 Articolo in rivista|