| Autor: |
Burgey, C. S., Robinson, K. A., Lyle, T. A., Sanderson, P. E. J., Lewis, S. D., Lucas, B. J., Krueger, J. A., Singh, R., Miller-Stein, C., White, R. B., Wong, B., Lyle, E., Williams, P. D., Coburn, C. A., Dorsey, B. D., Barrow, J. C., Stranieri, M. T., Holahan, M. A., Sitko, G. R., Cook, J. J., McMasters, D. R., McDonough, C. M., Sanders, W. M., Wallace, A. A., Clayton, F. C., Bohn, D., Leonard, Y. M., Detwiler, T. J., Jr., Lynch, J. J., Jr., Yan, Y., Chen, Z., Kuo, L., Gardell, S. J., Shafer, J. A., Vacca, J. P. |
| Zdroj: |
Journal of Medicinal Chemistry; February 2003, Vol. 46 Issue: 4 p461-473, 13p |
| Abstrakt: |
Recent efforts in the field of thrombin inhibitor research have focused on the identification of compounds with good oral bioavailability and pharmacokinetics. In this manuscript we describe a metabolism-based approach to the optimization of the 3-(2-phenethylamino)-6-methylpyrazinone acetamide template (e.g., 1) which resulted in the modification of each of the three principal components (i.e., P1, P2, P3) comprising this series. As a result of these studies, several potent thrombin inhibitors (e.g., 20, 24, 25) were identified which exhibit high levels of oral bioavailability and long plasma half-lives. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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