| Autor: |
Coleman, P. J., Brashear, K. M., Askew, B. C., Hutchinson, J. H., McVean, C. A., Duong, L. T., Feuston, B. P., Fernandez-Metzler, C., Gentile, M. A., Hartman, G. D., Kimmel, D. B., Leu, C.-T., Lipfert, L., Merkle, K., Pennypacker, B., Prueksaritanont, T., Rodan, G. A., Wesolowski, G. A., Rodan, S. B., Duggan, M. E. |
| Zdroj: |
Journal of Medicinal Chemistry; September 2004, Vol. 47 Issue: 20 p4829-4837, 9p |
| Abstrakt: |
3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)-(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the αvβ3 receptor. These compounds have excellent in vitro profiles (IC50 = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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