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.

The synthesis and preliminary evaluation of a series of 3-phenyl-4,5-dihydro-1H-pyrazole derivatives as potential inhibitors of both neuronal and inducible nitric oxide synthases (nNOS and iNOS) is described. Some of them show selectivity against iNOS. Two of these compounds have demonstrated to prevent the increment of the inducible NOS activity in both cytosol (iNOS) and mitochondria (i-mtNOS) observed in the MPTP model of Parkinson's disease.Figure optionsDownload as PowerPoint slide