The chemical evolution of N, N-dimethyl-2-[5-(1, 2, 4-triazol-4-yl)-1H-indol-3-yl] ethylamine (L-741,604) and analogues: Potent and selective agonists for 5-HT 1D …

F Sternfeld, R Baker, HB Broughton, AR Guiblin…

Index: Sternfeld, Francine; Baker, Raymond; Broughton, Howard B.; Guiblin, Alexander R.; Jelley, Richard A.; Matassa, Victor G.; Reeve, Austin J.; Beer, Margaret S.; Stanton, Josephine A.; Hargreaves, Richard J.; Shepheard, Sara L.; Longmore, Jeanette; Razzaque, Zerin; Graham, Michael I.; Sohal, Bindi; Street, Leslie J. Bioorganic and Medicinal Chemistry Letters, 1996 , vol. 6, # 15 p. 1825 - 1830

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Citation Number: 22

Abstract

Optimisation of a series of 5-(heterocyclyl) tryptamines led to the identification of the symmetrically substituted, N-4 linked 1, 2, 4-triazole as the best indole C-5 substituent for 5- HT1D receptor affinity and selectivity. The triazole (8) is the most potent and selective, orally bioavailable, 5-HT1D receptor agonist identified to date, showing an order of magnitude greater potency than the clinical compound sumatriptan with improved subtype selectivity.