Synthesis and Pharmacology of 6-Substituted Benztropines: Discovery of Novel Dopamine Uptake Inhibitors Possessing Low Binding Affinity to the Dopamine Transporter | Zendy

Daniele Simoni | Zendy; Marcello Rossi | Zendy; V. Bertolasi | Zendy; Marinella Roberti | Zendy; Daniela Pizzirani | Zendy; Riccardo Rondanin | Zendy; Riccardo Baruchello | Zendy; Francesco Paolo Invidiata | Zendy; Manlio Tolomeo | Zendy; Stefania Grimaudo | Zendy; Stefania Merighi | Zendy; Katia Varani | Zendy; Stefania Gessi | Zendy; Pier Andrea Borea | Zendy; Silvia Marino | Zendy; Sabrina Cavallini | Zendy; Clementina Bianchi | Zendy; Anna Siniscalchi | Zendy

Open Access

Synthesis and Pharmacology of 6-Substituted Benztropines: Discovery of Novel Dopamine Uptake Inhibitors Possessing Low Binding Affinity to the Dopamine Transporter

Author(s) -

Daniele Simoni,

Marcello Rossi,

V. Bertolasi,

Marinella Roberti,

Daniela Pizzirani,

Riccardo Rondanin,

Riccardo Baruchello,

Francesco Paolo Invidiata,

Manlio Tolomeo,

Stefania Grimaudo,

Stefania Merighi,

Katia Varani,

Stefania Gessi,

Pier Andrea Borea,

Silvia Marino,

Sabrina Cavallini,

Clementina Bianchi,

Anna Siniscalchi

Publication year - 2005

Publication title -

journal of medicinal chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.01

H-Index - 261

eISSN - 1520-4804

pISSN - 0022-2623

DOI - 10.1021/jm0490235

Subject(s) - chemistry , benztropine , tropane , dopamine transporter , enantiomer , dopamine , stereochemistry , dopamine plasma membrane transport proteins , transporter , dopamine uptake inhibitors , biochemistry , receptor , nucleus accumbens , neuroscience , gene , biology

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.

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