| Autor: |
Webber, R. K., Metz, S., Moore, W. M., Connor, J. R., Currie, M. G., Fok, K. F., Hagen, T. J., Hansen, D. W., Jr., Jerome, G. M., Manning, P. T., Pitzele, B. S., Toth, M. V., Trivedi, M., Zupec, M. E., Tjoeng, F. S. |
| Zdroj: |
Journal of Medicinal Chemistry; January 1, 1998, Vol. 41 Issue: 1 p96-101, 6p |
| Abstrakt: |
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 exibited IC50 values of 0.1 and 0.08 μM, 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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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