The enantiomers of the potent cognition-enhancer DM232 ((1), unifiram) and of its isopropylsulfonyl analog (2), which is endowed with amnesic properties, have been synthesized using (S)- and (R)-5-(hydroxymethyl)-2-pyrrolidinone as chiral precursors. The enantiomeric excess was determined by means of capillary electrophoresis, and found higher than 99.9 %. DM232 enantiomers were tested as cognition-enhancers in the passive-avoidance and social learning tests, and their ability to induce ACh release from rat cerebral cortex was also determined; in all the performed essays, (R)-(+)-(1) displayed higher potency than its (S)-(-) enantiomer, being able to elicit comparable effects at 3-fold to 10-fold lower doses. On the contrary, (R)-(+) and (S)-(-)-(2) showed the same amnesic potency when tested in the passive-avoidance test. These findings may be useful to clarify the mechanism of action of these substances.

Enantioselective synthesis and preliminary pharmacological evaluation of the enantiomers of unifiram (DM232), a potent cognition-enhancing agent / Martini, Elisabetta; Ghelardini, Carla; Bertucci, C.; Dei, Silvia; Gualtieri, Fulvio; Guandalini, Luca; Manetti, Dina; Scapecchi, Serena; Teodori, Elisabetta; Romanelli, MARIA NOVELLA. - In: MEDICINAL CHEMISTRY. - ISSN 1573-4064. - STAMPA. - 1(2005), pp. 473-480.

Enantioselective synthesis and preliminary pharmacological evaluation of the enantiomers of unifiram (DM232), a potent cognition-enhancing agent

MARTINI, ELISABETTA;GHELARDINI, CARLA;DEI, SILVIA;GUALTIERI, FULVIO;GUANDALINI, LUCA;MANETTI, DINA;SCAPECCHI, SERENA;TEODORI, ELISABETTA;ROMANELLI, MARIA NOVELLA
2005

Abstract

The enantiomers of the potent cognition-enhancer DM232 ((1), unifiram) and of its isopropylsulfonyl analog (2), which is endowed with amnesic properties, have been synthesized using (S)- and (R)-5-(hydroxymethyl)-2-pyrrolidinone as chiral precursors. The enantiomeric excess was determined by means of capillary electrophoresis, and found higher than 99.9 %. DM232 enantiomers were tested as cognition-enhancers in the passive-avoidance and social learning tests, and their ability to induce ACh release from rat cerebral cortex was also determined; in all the performed essays, (R)-(+)-(1) displayed higher potency than its (S)-(-) enantiomer, being able to elicit comparable effects at 3-fold to 10-fold lower doses. On the contrary, (R)-(+) and (S)-(-)-(2) showed the same amnesic potency when tested in the passive-avoidance test. These findings may be useful to clarify the mechanism of action of these substances.
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473
480
Martini, Elisabetta; Ghelardini, Carla; Bertucci, C.; Dei, Silvia; Gualtieri, Fulvio; Guandalini, Luca; Manetti, Dina; Scapecchi, Serena; Teodori, Elisabetta; Romanelli, MARIA NOVELLA
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/314543
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