| Autor: |
Chambers, M. S., Street, L. J., Goodacre, S., Hobbs, S. C., Hunt, P., Jelley, R. A., Matassa, V. G., Reeve, A. J., Sternfeld, F., Beer, M. S., Stanton, J. A., Rathbone, D., Watt, A. P., MacLeod, A. M. |
| Zdroj: |
Journal of Medicinal Chemistry; February 25, 1999, Vol. 42 Issue: 4 p691-705, 15p |
| Abstrakt: |
Clinically effective antimigraine drugs such as Sumatriptan have similar affinity at h5-HT1D and h5-HT1B receptors. In the search for a h5-HT1D-selective agonist as an antimigraine agent, a novel series of 3-(propylpiperazinyl)indoles have been synthesized and evaluated at h5-HT1D and h5-HT1B receptors. This class of compounds has provided subnanomolar, fully efficacious h5-HT1D agonists with up to 200-fold selectivity for the h5-HT1D receptor over the h5-HT1B receptor. Unlike other h5-HT1D-selective series, several propylpiperazines demonstrate good oral bioavailability. The optimum compound was 1-(3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl)-4-(2-(3-fluorophenyl)ethyl)piperazine (7f) which has excellent selectivity for h5-HT1D receptors over other 5-HT receptor subtypes and good oral bioavailability in three species. Compound 7f has been selected for further investigation as a potential development candidate in the treatment of migraine. |
| Databáze: |
Supplemental Index |
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