title: Synthesis, biological evaluation and structure-activity relationships of new phthalazinedione derivatives with vasorelaxant activity.
abstract: Five series of 1,4-phthalazinedione derivatives were synthesized in good yields. Vasorelaxant activity of these new derivatives was measured on either intact or endothelium-denuded isolated rat thoracic aortic rings pre-contracted with phenylephrine. Most of studied compounds, substituted in both nitrogen atoms, attained practically the total relaxation of the organ at low micromolar concentrations. The presence of functional endothelium significantly reduced the EC50 values for most of studied compounds. Some structure-activity relationships were established and compounds 2d and 5d can be considered as new leads for further modifications.
authors.affiliation: Farmacología de las Enfermedades Crónicas, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain; Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Munín
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: elias.quezada@usc.es.
authors.forename: Elías
authors.initials: E
authors.lastname: Quezada
authors.affiliation: Farmacología de las Enfermedades Crónicas, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cuiñas
authors.affiliation: Farmacología de las Enfermedades Crónicas, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Campos-Toimil
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.affiliation: Farmacología de las Enfermedades Crónicas, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: mdolores.vina@usc.es.
authors.forename: Dolores
authors.initials: D
authors.lastname: Viña
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D008297:Male; D015394:Molecular Structure; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D010793:Phthalazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D010793:Phthalazines; D014665:Vasodilator Agents
keywords: Endothelium; Phthalazinedione derivatives; Rat aortic rings; SAR; Synthesis; Vasorelaxant activity