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Medicinal Chemistry
ISSN (Print): 1573-4064
ISSN (Online): 1875-6638
VOLUME: 1
ISSUE: 5
DOI: 10.2174/1573406054864142      Price:  $58









Enantioselective Synthesis and Preliminary Pharmacological Evaluation of the Enantiomers of Unifiram (DM232), a Potent Cognition-Enhancing Agent

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Author(s): E. Martini, C. Ghelardini, C. Bertucci, S. Dei, F. Gualtieri, L. Guandalini, D. Manetti, S. Scapecchi, E. Teodori and M. N. Romanelli
Pages 473-480 (8)
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 passiveavoidance test. These findings may be useful to clarify the mechanism of action of these substances.
Keywords:
cognition-enhancer, nootropic, chiral synthesis
Affiliation:
Dipartimento di Scienze Farmaceutiche, Universita di Firenze, Via Ugo Schiff 6, 50019 SestoFiorentino (FI), Italy.