A. Slassi et al. / Bioorg. Med. Chem. Lett. 10 (2000) 1707±1709
1709
than sumatriptan (8.7-fold), with a general trend for
increasing selectivity with increasing size of alkyl group
(Et, iPr, tBu).
9. Rebeck, G. W.; Maynard, K. I.; Hyman, B. T.; Moskowitz,
M. A. Proc. Natl. Acad. Sci. USA 1994, 91, 3666.
10. (a) Hamel, E. Serotonin 1996, 1, 19. (b) Hamel, E.; Gregoire,
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11. Phebus, L. A.; Johnson, K. W.; Audia, M. L. Cephalalgia
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12. Castro, J. L.; Collins, I.; Russell, M. G. N.; Watt, A. P.;
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The functional activities of selected compounds (6d, 6e,
8a±8d and sumatriptan) were evaluated both as antago-
nists and as agonists using isolated rabbit saphenous vein
(RSV) preparation as measures of functional activity. All
compounds showed agonist activity with EC50 values
(Table 1), with no demonstrated antagonist activity.
In summary, a series of highly potent and selective 5-
alkyltryptamine derivatives have been developed using a
variety of tertiary amine side chains. The constrained
analogues derived from d-proline provided several com-
pounds with subnanomolar potency and high selectivity.
Compound 6e is currently being further evaluated in
animal models for the treatment of migraine.
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