Piperazines as nootropic agents: New derivatives of the potent cognition-enhancer DM235 carrying hydrophilic substituents

Publication date: Available online 16 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Maria Vittoria Martino, Luca Guandalini, Lorenzo Di Cesare Mannelli, Marta Menicatti, Gianluca Bartolucci, Silvia Dei, Dina Manetti, Elisabetta Teodori, Carla Ghelardini, Maria Novella Romanelli
The piperazine ring of the potent nootropic drug DM235has 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.

Graphical abstract

http://ift.tt/2lRyKam