Discovery of a series of aminopiperidines as novel iNOS inhibitors.

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Le Bourdonnec B, Leister LK, Ajello CA, Cassel JA, Seida PR, O'Hare H, Gu M, Chu GH, Tuthill PA, DeHaven RN, Dolle RE

Discovery of a series of aminopiperidines as novel iNOS inhibitors.

Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43. Epub 2007 Oct 25.

PubMed ID

18024030 [ View in PubMed

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Abstract

Nitric oxide (NO), a mediator of various physiological and pathophysiological processes, is synthesized by three isozymes of nitric oxide synthase (NOS). Potential candidate clinical drugs should be devoid of inhibitory activity against endothelial NOS (eNOS), since eNOS plays an important role in maintaining normal blood pressure and flow. A new series of aminopiperidines as potent inhibitors of iNOS were identified from a HTS lead. From this study, we identified compound 33 as a potent iNOS inhibitor, with >25-fold selectivity over eNOS and 16-fold selectivity over nNOS.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
1-(6-CYANO-3-PYRIDYLCARBONYL)-5',8'-DIFLUOROSPIRO[PIPERIDINE-4,2'(1'H)-QUINAZOLINE]-4'-AMINE	Nitric oxide synthase, inducible	IC 50 (nM)	170	N/A	N/A	Details
1-(6-CYANO-3-PYRIDYLCARBONYL)-5',8'-DIFLUOROSPIRO[PIPERIDINE-4,2'(1'H)-QUINAZOLINE]-4'-AMINE	Nitric oxide synthase, inducible	IC 50 (nM)	210	N/A	N/A	Details