Filla, Sandra A.; Mathes, Brian M.; Johnson, Kirk W.; Phebus, Lee A.; Cohen, Marlene L.; Nelson, David L.; Zgombick, John M.; Erickson, Jon A.; Schenck, Kathryn W.; Wainscott, David B.; Branchek, Theresa A.; Schaus, John M. published the artcile< Novel Potent 5-HT1F Receptor Agonists: Structure-Activity Studies of a Series of Substituted N-[3-(1-Methyl-4-piperidinyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]amides>, Formula: C6H7N3O2, the main research area is pyrrolopyridine amido sulfonamido preparation 5HT receptor agonist migraine; pyrrolopyrimidine amido preparation 5HT receptor agonist migraine.
5-Amidoindole I [X = Y = CH, R = 4-FC6H4; (II)] (LY334370), a selective 5-HT1F receptor agonist (SSOFRA), inhibited dural inflammation in the neurogenic plasma protein extravasation model of migraine and demonstrated clin. efficacy for the acute treatment of migraine. Although II was greater than 100-fold selective over both the 5-HT1B and 5-HT1D receptors, it exhibited appreciable 5-HT1A receptor affinity. Thus, a series of pyrrolo[2,3-c]pyridines I (X = N; Y = CH; R = Me, 4-FC6H4) and pyrrolo[3,2-b]pyridines I (X = CH; Y = N; R = Me, Et, Ph, 3-thienyl, 2-furyl, 2-pyridyl, cyclopropyl, etc.) as well as pyrrolo[3,2-d]pyrimidines I (X = Y = N; R = Me, 4-FC6H4) were synthesized as analogs of II and evaluated in an effort to identify SSOFRAs with improved selectivity over other 5-HT1 receptor subtypes. I (X = CH, Y = N, R = 4-FC6H4) showed high 5-HT1F receptor affinity but offered no improvement in selectivity compared to II; however, I (X = CH, Y = N, R = Me) was greater than 100-fold selective over the 5-HT1A, 5-HT1B, and 5-HT1D receptors. SAR studies of this series determined that alkylamides in particular exhibited high selectivity for the 5-HT1F receptor. These SAR studies identified SSOFRAs that demonstrated oral activity in the neurogenic plasma protein extravasation model, a model indicative of antimigraine activity.
Journal of Medicinal Chemistry published new progress about 5-HT1 agonists. 22280-62-2 belongs to class pyridine-derivatives, and the molecular formula is C6H7N3O2, Formula: C6H7N3O2.