| Literature DB >> 10052976 |
M S Chambers1, L J Street, S Goodacre, S C Hobbs, P Hunt, R A Jelley, V G Matassa, A J Reeve, F Sternfeld, M S Beer, J A Stanton, D Rathbone, A P Watt, A M MacLeod.
Abstract
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)p ipe razine (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.Entities:
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Year: 1999 PMID： 10052976 DOI： 10.1021/jm980569z
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446