title: Piperazines as nootropic agents: New derivatives of the potent cognition-enhancer DM235 carrying hydrophilic substituents.
abstract: The piperazine ring of the potent nootropic drug DM235 has been decorated with H-bond donor and acceptor groups (CH2OH, CH2OMe, CH2OCOMe, COOEt); the aim was to insert new functional groups, suitable for further chemical manipulation. The influence of these modifications on nootropic activity was assessed by means of the mouse passive avoidance test; some of the newly synthesized molecules (alcohol 7b, acetate 8b and ester 10d) showed interesting in vivo potency. This makes it possible to use these functional groups for adding other residues, in order to increase molecular diversity, or for anchoring a biotin group, to obtain compounds useful to capture the biological target. Moreover, the new compounds will improve our knowledge of structure activity relationships of this family of drugs.
authors.affiliation: University of Florence, Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmaceutical and Nutraceutical Sciences, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Martino
authors.affiliation: University of Florence, Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmaceutical and Nutraceutical Sciences, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Guandalini
authors.affiliation: University of Florence, Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmacology and Toxicology, Viale Gaetano Pieraccini 6, 50100 Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.affiliation: University of Florence, Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmaceutical and Nutraceutical Sciences, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Menicatti
authors.affiliation: University of Florence, Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmaceutical and Nutraceutical Sciences, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bartolucci
authors.affiliation: University of Florence, Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmaceutical and Nutraceutical Sciences, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dei
authors.affiliation: University of Florence, Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmaceutical and Nutraceutical Sciences, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Dina
authors.initials: D
authors.lastname: Manetti
authors.affiliation: University of Florence, Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmaceutical and Nutraceutical Sciences, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Teodori
authors.affiliation: University of Florence, Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmacology and Toxicology, Viale Gaetano Pieraccini 6, 50100 Florence, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.affiliation: University of Florence, Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmaceutical and Nutraceutical Sciences, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy. Electronic address: novella.romanelli@unifi.it.
authors.forename: Maria Novella
authors.initials: MN
authors.lastname: Romanelli
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D003071:Cognition / Q000187:drug effects*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D018697:Nootropic Agents / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D018697:Nootropic Agents; D010879:Piperazines; C416655:DM 235
keywords: Cognition-enhancers; Mouse passive-avoidance test; Piperazines; Piracetam-like compounds; Sunifiram