title: Synthesis of new 1,2,3-benzotriazin-4-one-arylpiperazine derivatives as 5-HT1A serotonin receptor ligands.
abstract: A series of novel 1,2,3-benzotriazin-4-one derivatives was prepared and evaluated as ligands for 5-HT receptors. Radioligand binding assays proved that the majority of the novel compounds behaved as good to excellent ligands at the 5-HT1A receptor, some of which were selective with respect 5-HT2A and 5-HT2C receptors. Six analogues (1a, 2a, 2b, 2c, 2e and 2i) were selected and further evaluated for their binding affinities on D1, D2 dopaminergic and alpha1-, alpha2-adrenergic receptors. A o-OCH3 derivative (2e) bound at 5-HT1A sites with subnanomolar affinity (IC50 = 0.059 nM) and shows high selectivity over all considered receptors and may offer a new lead for the development of therapeutically efficacious agents.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Naples, Italy. caliendo@unina.it
authors.forename: G
authors.initials: G
authors.lastname: Caliendo
authors.forename: F
authors.initials: F
authors.lastname: Fiorino
authors.forename: P
authors.initials: P
authors.lastname: Grieco
authors.forename: E
authors.initials: E
authors.lastname: Perissutti
authors.forename: V
authors.initials: V
authors.lastname: Santagada
authors.forename: B
authors.initials: B
authors.lastname: Severino
authors.forename: G
authors.initials: G
authors.lastname: Bruni
authors.forename: M R
authors.initials: MR
authors.lastname: Romeo
mesh_terms: D000818:Animals; D001921:Brain / Q000648:ultrastructure; D002462:Cell Membrane / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008024:Ligands; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011941:Receptors, Adrenergic / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D014793:Visual Cortex / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D008024:Ligands; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011941:Receptors, Adrenergic; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D014227:Triazines; C102393:1,2,3-benzotriazin-4-one