title: Substituted furo[3,2-b]pyridines: novel bioisosteres of 5-HT 1F receptor agonists.
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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. mathes_brian_m@lilly.com
authors.forename: Brian M
authors.initials: BM
authors.lastname: Mathes
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Hudziak
authors.forename: John M
authors.initials: JM
authors.lastname: Schaus
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Xu
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.forename: David B
authors.initials: DB
authors.lastname: Wainscott
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Nutter
authors.forename: Wendy H
authors.initials: WH
authors.lastname: Gough
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Branchek
authors.forename: John M
authors.initials: JM
authors.lastname: Zgombick
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Filla
mesh_terms: D011485:Protein Binding / Q000502:physiology; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000737:chemistry* / Q000378:metabolism*; D000096642:Receptor, Serotonin, 5-HT1F
chemical_list: D011725:Pyridines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D000096642:Receptor, Serotonin, 5-HT1F