title: Design and synthesis of S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-a]pyrazine (CSP-2503) using computational simulation. A 5-HT1A receptor agonist.
abstract: Based on a computational model for 5-HT(1A)R-ligand interaction and QSAR studies, we have designed and synthesized a new series of arylpiperazines 2-8 which exhibit high 5-HT(1A)R affinity and selectivity over alpha(1)-adrenergic receptors. Among them, compound CSP-2503 (4) has been pharmacologically characterized as a 5-HT(1A)R agonist at somatodendritic and postsynaptic sites, endowed with anxiolytic properties.
authors.affiliation: Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense, E-28040 Madrid, Spain. mluzir@quim.ucm.es
authors.forename: María L
authors.initials: ML
authors.lastname: López-Rodríguez
authors.forename: Ma José
authors.initials: MJ
authors.lastname: Morcillo
authors.forename: Esther
authors.initials: E
authors.lastname: Fernández
authors.forename: Bellinda
authors.initials: B
authors.lastname: Benhamú
authors.forename: Ignacio
authors.initials: I
authors.lastname: Tejada
authors.forename: David
authors.initials: D
authors.lastname: Ayala
authors.forename: Alma
authors.initials: A
authors.lastname: Viso
authors.forename: Mireia
authors.initials: M
authors.lastname: Olivella
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pardo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Delgado
authors.forename: Jorge
authors.initials: J
authors.lastname: Manzanares
authors.forename: José A
authors.initials: JA
authors.lastname: Fuentes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001555:Benzene Derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000187:drug effects* / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: C479225:2-((4-(naphth-1-yl)piperazin-1-yl)methyl)-1,4-dioxoperhydropyrrolo(1,2-a)pyrazine; D014151:Anti-Anxiety Agents; D001555:Benzene Derivatives; D010879:Piperazines; D011719:Pyrazines; D018340:Receptors, Adrenergic, alpha-1; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists