| Autor: |
Christensen, S. B., Guider, A., Forster, C. J., Gleason, J. G., Bender, P. E., Karpinski, J. M., DeWolf, W. E., Jr., Barnette, M. S., Underwood, D. C., Griswold, D. E., Cieslinski, L. B., Burman, M., Bochnowicz, S., Osborn, R. R., Manning, C. D., Grous, M., Hillegas, L. M., Bartus, J. O., Ryan, M. D., Eggleston, D. S., Haltiwanger, R. C., Torphy, T. J. |
| Zdroj: |
Journal of Medicinal Chemistry; March 12, 1998, Vol. 41 Issue: 6 p821-835, 15p |
| Abstrakt: |
Evaluation of a variety of PDE4 inhibitors in a series of cellular and in vivo assays suggested a strategy to improve the therapeutic index of PDE4 inhibitors by increasing their selectivity for the ability to inhibit PDE4 catalytic activity versus the ability to compete for high affinity [3H]rolipram-binding sites in the central nervous system. Use of this strategy led ultimately to the identification of cis-4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1-carboxylic acid (1, SB 207499, ArifloTM), a potent second-generation inhibitor of PDE4 with a decreased potential for side effects versus the archetypic first generation inhibitor, (R)-rolipram. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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