title: 1,3,4-Thiadiazole derivatives as selective inhibitors of iNOS versus nNOS: Synthesis and structure-activity dependence.
abstract: The synthesis of new compounds with a 1,3,4-thiadiazole structure, and their in vitro biological evaluation as inhibitors of both neuronal and inducible Nitric Oxide Synthase (nNOS and iNOS) is described. These compounds have been designed by an isosteric modification of a series of 4,5-dihydro-1H-pyrazole derivatives, previously described as the nNOS inhibitors. The insertion of the S atom in the heterocyclic ring induces a selective inhibition of the iNOS isoform. Some of these compounds show as iNOS inhibition percentage near of 100% at a concentration of 50 μM, and the IC(50) values measured for the more potent compounds are in a range of 20-40 μM.
authors.affiliation: Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Spain.
authors.forename: Luisa C
authors.initials: LC
authors.lastname: López-Cara
authors.forename: M Dora
authors.initials: MD
authors.lastname: Carrión
authors.forename: Antonio
authors.initials: A
authors.lastname: Entrena
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gallo
authors.forename: Antonio
authors.initials: A
authors.lastname: Espinosa
authors.forename: Ana
authors.initials: A
authors.lastname: López
authors.forename: Germaine
authors.initials: G
authors.lastname: Escames
authors.forename: Darío
authors.initials: D
authors.lastname: Acuña-Castroviejo
authors.forename: M Encarnación
authors.initials: ME
authors.lastname: Camacho
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D013830:Thiadiazoles; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II