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ID: ALA1138691

Journal: Bioorg Med Chem Lett

Title: Substituted furo[3,2-b]pyridines: novel bioisosteres of 5-HT 1F receptor agonists.

Authors: Mathes BM, Hudziak KJ, Schaus JM, Xu YC, Nelson DL, Wainscott DB, Nutter SE, Gough WH, Branchek TA, Zgombick JM, Filla SA.

Abstract: 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.

CiteXplore: 14684321

DOI: 10.1016/j.bmcl.2003.09.091