Phenylpyrrole derivatives as neural and inducible nitric oxide synthase (nNOS and iNOS) inhibitors.
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.
López Cara
Luisa C
LC
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
Camacho
M Encarnación
ME
Carrión
M Dora
MD
Tapias
Víctor
V
Gallo
Miguel A
MA
Escames
Germaine
G
Acuña-Castroviejo
Darío
D
Espinosa
Antonio
A
Entrena
Antonio
A
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
D004791:Enzyme Inhibitors; D011720:Pyrazoles; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II