Martino Maria Vittoria, Guandalini Luca, Di Cesare Mannelli Lorenzo, Menicatti Marta, Bartolucci Gianluca, Dei Silvia, Manetti Dina, Teodori Elisabetta, Ghelardini Carla, Romanelli Maria Novella
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.
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.
Bioorg Med Chem. 2017 Mar 15;25(6):1795-1803. doi: 10.1016/j.bmc.2017.02.019. Epub 2017 Feb 16.
The piperazine ring of the potent nootropic drug DM235 has been decorated with H-bond donor and acceptor groups (CHOH, CHOMe, CHOCOMe, 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.
强效益智药DM235的哌嗪环已用氢键供体和受体基团（CHOH、CHOMe、CHOCOMe、COOEt）修饰；目的是引入适合进一步化学操作的新官能团。通过小鼠被动回避试验评估了这些修饰对益智活性的影响；一些新合成的分子（醇7b、乙酸酯8b和酯10d）显示出有趣的体内活性。这使得可以使用这些官能团添加其他残基，以增加分子多样性，或锚定生物素基团，从而获得可用于捕获生物靶点的化合物。此外，新化合物将增进我们对该类药物构效关系的了解。
