ACS Chem Neurosci 2021 Sep 16. Epub 2021 Sep 16.
School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Via S. Agostino 1, Camerino 62032, Italy.
In the search for novel bitopic compounds targeting the dopamine D receptor (DR), the -(2,3-dichlorophenyl)piperazine nucleus (primary pharmacophore) has been linked to the 6,6- or 5,5-diphenyl-1,4-dioxane-2-carboxamide or the 1,4-benzodioxane-2-carboxamide scaffold (secondary pharmacophore) by an unsubstituted or 3-F-/3-OH-substituted butyl chain. This scaffold hybridization strategy led to the discovery of potent DR-selective or multitarget ligands potentially useful for central nervous system disorders. In particular, the 6,6-diphenyl-1,4-dioxane derivative showed a DR-preferential profile, while an interesting multitarget behavior has been highlighted for the 5,5-diphenyl-1,4-dioxane and 1,4-benzodioxane derivatives and , respectively, which displayed potent DR antagonism, 5-HTR and DR agonism, as well as potent DR partial agonism. Read More