Substituted 2-iminopiperidines as inhibitors of human nitric oxide synthase isoforms.

doi:10.1021/JM9705059

Paper

Substituted 2-iminopiperidines as inhibitors of human nitric oxide synthase isoforms.

Published 1998 · R. K. Webber, S. Metz, W. M. Moore

Journal of medicinal chemistry

Q1 SJR score

47

Citations

2

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Abstract

A series of analogues of 2-iminopiperidine have been prepared and shown to be potent inhibitors of the human nitric oxide synthase (NOS) isoforms. Methyl substitutions on the 4-position (3) or 4- and 6-positions (8) afforded the most potent analogues. These compounds exhibited IC50 values of 0.1 and 0.08 microM, respectively, for hiNOS inhibition. Substitution with cyclohexylmethyl at the 6-position (13) afforded an inhibitor that showed the best selectivity for hiNOS versus heNOS (heNOS IC50/hiNOS IC50 = 64). Following oral administration, inhibitors were found to decrease serum nitrite/nitrate levels in an in vivo rat endotoxin assay. This series of 2-iminopiperidines were prepared via the described synthetic methodologies. The effect of ring substitutions on potency and selectivity for this class of cyclic amidines as NOS inhibitors is described.

In Vitro Study

Study Snapshot

Substituted 2-iminopiperidines show potent inhibitory effects on human nitric oxide synthase, with methyl substitutions on the 4- and 6-positions yielding the most potent analogues.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Substituted 2-iminopiperidines as inhibitors of human nitric oxide synthase isoforms.

References

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