title: Synthesis and biological evaluation of new quinazoline and cinnoline derivatives as potential atypical antipsychotics.
abstract: Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained aminobutyrophenone derivatives QF0104B (5) and QF0108B (6) were synthesized (Schemes 2 and 3), and evaluated for their binding affinities (Table) towards the serotonin 5-HT2A and 5-HT2C, and the dopamine D2 receptors. Among the new compounds, the quinazoline derivative 15 (= 7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydroquinazolin-5-one) exhibited the highest affinities towards the serotonin 5-HT2A and dopamine D2 receptors, and it is in the borderline of potential atypical antipsychotics. The cinnoline derivative 23 (= 7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydro-3-methylcinnolin-5-one) displayed high selectivity in its binding profile towards the 5-HT2C compared to both the 5-HT2A and D2 receptors.
authors.affiliation: Departamento de Química Orgánica, Laboratorio de Química Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, E-15782, Santiago de Compostela, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Alvarado
authors.forename: María
authors.initials: M
authors.lastname: Barceló
authors.forename: Laura
authors.initials: L
authors.lastname: Carro
authors.forename: Christian F
authors.initials: CF
authors.lastname: Masaguer
authors.forename: Enrique
authors.initials: E
authors.lastname: Raviña
mesh_terms: D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D006574:Heterocyclic Compounds, 2-Ring; D011799:Quinazolines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; C476282:cinnoline