title: Phenylpyrrole derivatives as neural and inducible nitric oxide synthase (nNOS and iNOS) inhibitors.
abstract: We have previously described a series of 3-phenyl-4,5-dihydro-1H-pyrazole derivatives as moderately potent nNOS inhibitors. As a follow up of these studies, several new 5-phenyl-1H-pyrrole-2-carboxamide derivatives have been synthesized, and their biological evaluation as in vitro inhibitors of both neural and inducible Nitric Oxide Synthase (nNOS and iNOS) is described. Some of these compounds show good iNOS/nNOS selectivity and the more potent compounds 5-(2-aminophenyl)-1H-pyrrole-2-carboxilic acid methylamide (QFF205) and cyclopentylamide (QFF212) have been tested as regulators of the in vivo nNOS and iNOS activity. Both compounds prevented the increment of the inducible NOS activity in both cytosol (iNOS) and mitochondria (i-mtNOS) observed in the MPTP model of Parkinson's disease.
authors.affiliation: Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
authors.forename: Luisa C
authors.initials: LC
authors.lastname: López Cara
authors.forename: M Encarnación
authors.initials: ME
authors.lastname: Camacho
authors.forename: M Dora
authors.initials: MD
authors.lastname: Carrión
authors.forename: Víctor
authors.initials: V
authors.lastname: Tapias
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gallo
authors.forename: Germaine
authors.initials: G
authors.lastname: Escames
authors.forename: Darío
authors.initials: D
authors.lastname: Acuña-Castroviejo
authors.forename: Antonio
authors.initials: A
authors.lastname: Espinosa
authors.forename: Antonio
authors.initials: A
authors.lastname: Entrena
mesh_terms: D000818:Animals; D001665:Binding Sites; D003600:Cytosol / Q000201:enzymology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II