5-Thienyltryptamine derivatives as serotonin 5-HT1B/1D receptor agonists: potential treatments for migraine

A series of 5-(2- or 3-thienyl)tryptamine derivatives (9) has been synthesized and shown to be potent and selective 5-HT1D versus 5-HT1B receptor agonists and, therefore, potential treatments for migraine. Scheme 1. Reagents and conditions: (a) oxalylchloride, diethylether, 0 °C, then reflux overnight; (b) amines, triethylamine in tetrahydrofuran, RT/2 h; (c) Bu3SnSnBu3, PdPh3P4, toluene, reflux overnight; (d) thiopheneboronic acid, PdPh3P4, Na2CO3, DME, reflux/4 h; (e) thiophenebromide, PdPh3P4, Na2CO3, DMF, reflux/overnight; LAH, tetrahydrofuran, reflux/4 h.