Discovery of N1-(6-Chloroimidazo[2,1-b][1,3]-thiazole-5-sulfonyl)tryptamine as a Potent,Selective,and Orally Active 5-HT6 Receptor Agonist

摘要

N1-Arylsulfonyltryptamines have been identified as 5-HT6 receptor ligands.In particular,N1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine(11q)is a high affinity,potent full agonist(5-HT6 K_i=2 nM,EC50=6.5 nM,E_(max)=95.5%).Compound 11q is selective in a panel of over 40 receptors and ion channels,has good pharmacokinetic profile,has been shown to increase GABA levels in the rat frontal cortex,and is active in the schedule-induced polydipsia model for obsessive compulsive disorders.