Design, synthesis and biological evaluation of bitopic arylpiperazine-hexahydro-pyrazinoquinolines as preferential dopamine D3 receptor ligands

Three series of bitobic arylpiperazine-phenyl-hexahydropyrazinoquino- lines analogues were designed, synthesized and evaluated as a novel class of selective ligands for the dopamine D3 receptor. Compounds 15a (K-i of 11.7 +/- 1.8 and 373 nM at D3 and D2, respectively), 15c (K-i of 5.49 and 264 nM at D3 and D2, respectively), 15e (K-i of 14.9 and 325 nM at D3 and D2, respectively), 15i (K-i of 13.8 and 401 nM at D3 and D2, respectively) and 15l (K-i of 13.6 and 870 nM at D3 and D2, respectively) were found to demonstrate good binding affinity and selectivity, and especially compound 15c showed a similar binding affinity and selectivity compared with the contrast drug BP897. (C) 2018 Elsevier Inc. All rights reserved.