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

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

Volume: 1 Issue: 5

Author(s): E. Martini, C. Ghelardini, C. Bertucci, S. Dei, F. Gualtieri, L. Guandalini, D. Manetti, S. Scapecchi, E. Teodori and M. N. Romanelli

Affiliation:

Keywords: cognition-enhancer, nootropic, chiral synthesis

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.

Cite this article as:

Martini E., Ghelardini C., Bertucci C., Dei S., Gualtieri F., Guandalini L., Manetti D., Scapecchi S., Teodori E. and Romanelli N. M., Enantioselective Synthesis and Preliminary Pharmacological Evaluation of the Enantiomers of Unifiram (DM232), a Potent Cognition-Enhancing Agent, Medicinal Chemistry 2005; 1 (5) . https://dx.doi.org/10.2174/1573406054864142