Synthesis and serotonergic activity of 5-(oxadiazolyl)tryptamines: potent agonists for 5-HT1D receptors

摘要: The synthesis and 5-HT1D receptor activity of a novel series 5-(oxadiazolyl)tryptamines is described. Modifications the oxadiazole 3-substituent, length linking chain (n), amine substituents are explored reveal large binding pocket in domain. Oxadiazole such as benzyl accommodated without loss agonist potency or efficacy. incorporation polar functionality on phenyl spacer group results 10-fold increase affinity functional potency. Optimal observed when heterocycle conjugated with indole sulfonamides 20t 20u represent some most potent agonists known. Replacement O for S leads to further Deletion N-2 does not reduce activity, suggesting requirement only one H-bond acceptor this location. selectivity these compounds receptors over other serotonergic discussed. Sulfonamide shows > = 1000-fold 5-HT2, 5-HT1C, 5-HT3 respect 5-HT1A receptors. studied demonstrates high efficacy comparable that 5-HT.