Substituted furo[3,2-b]pyridines: novel bioisosteres of 5-HT1F receptor agonists

Synthesis and evaluation of a series of 2,3,5- and 3,5-substituted furo[3,2- b ]pyridines were undertaken in order to investigate their utility as bioisosteres of 5-HT 1F receptor agonist indole analogues, 1 – 3 . The replacement proved to be effective, providing compounds with similar 5-HT 1F receptor affinity and improved selectivity when compared with the indole analogues. Through these studies we identified 4-fluoro- N -[3-(1-methyl-piperidin-4-yl)-furo[3,2- b ]pyridin-5-yl]-benzamide ( 5 ), a potent and selective 5-HT 1F receptor agonist with the potential to treat acute migraine.