title: Kynurenamines as neural nitric oxide synthase inhibitors.
abstract: To find new compounds with potential neuroprotective activity, we have designed, synthesized, and characterized a series of neural nitric oxide synthase (nNOS) inhibitors with a kynurenamine structure. Among them, N-[3-(2-amino-5-methoxyphenyl)-3-oxopropyl]acetamide is the main melatonin metabolite in the brain and shows the highest activity in the series, with an inhibition percentage of 65% at a 1 mM concentration. The structure-activity relationship of the new series partially reflects that of the previously reported 2-acylamido-4-(2-amino-5-methoxyphenyl)-4-oxobutyric acids, endowed with a kynurenine-like structure. Structural comparisons between these new kinurenamine derivatives, kynurenines, and 1-acyl-3-(2-amino-5-methoxyphenyl)-4,5-dihydro-1H-pyrazole derivatives also reported confirm our previous model for the nNOS inhibition.
authors.affiliation: Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, 18071 Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Entrena
authors.forename: M Encarnación
authors.initials: ME
authors.lastname: Camacho
authors.forename: M Dora
authors.initials: MD
authors.lastname: Carrión
authors.forename: Luisa C
authors.initials: LC
authors.lastname: López-Cara
authors.forename: Guillermo
authors.initials: G
authors.lastname: Velasco
authors.forename: Josefa
authors.initials: J
authors.lastname: León
authors.forename: Germaine
authors.initials: G
authors.lastname: Escames
authors.forename: Darío
authors.initials: D
authors.lastname: Acuña-Castroviejo
authors.forename: Víctor
authors.initials: V
authors.lastname: Tapias
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gallo
authors.forename: Antonio
authors.initials: A
authors.lastname: Vivó
authors.forename: Antonio
authors.initials: A
authors.lastname: Espinosa
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007735:Kynuramine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D050601:Kynurenine 3-Monooxygenase / Q000037:antagonists & inhibitors; D008968:Molecular Conformation; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D007735:Kynuramine; C032131:N-acetyl-5-methoxy kynurenamine; D052248:Nitric Oxide Synthase Type I; D050601:Kynurenine 3-Monooxygenase