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-HT1D Receptors.

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.