Substituted furo[3,2-b]pyridines: novel bioisosteres of 5-HT 1F 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.
Mathes
Brian M
BM
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. mathes_brian_m@lilly.com
Hudziak
Kevin J
KJ
Schaus
John M
JM
Xu
Yao-Chang
YC
Nelson
David L
DL
Wainscott
David B
DB
Nutter
Suzanne E
SE
Gough
Wendy H
WH
Branchek
Theresa A
TA
Zgombick
John M
JM
Filla
Sandra A
SA
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
D011725:Pyridines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D000096642:Receptor, Serotonin, 5-HT1F