Solution phase parallel synthesis of substituted 3-phenylsulfonyl-[1,2,3] triazolo[1,5- a ]quinazolines: Selective serotonin 5-HT6 receptor antagonists

Article abstract of DOI:10.1021/cc1000049

Here we present the solution phase parallel synthesis of a combinatorial library consisting of 776 new substituted 3-phenylsulfonyl-[1,2,3]triazolo[1,5- a]quinazolines and a study of the relation of their structure with a 5-HT ₆ receptor antagonistic activity in a functional cell (HEK 293) analysis and radioligand competitive binding. We have found highly active and selective 5-HT₆R antagonists. The most active 5-HT₆R antagonists have IC₅₀ <100 nM in a functional assay, and K _i <10 nM in a binding assay, which is 100 times higher than the activity with respect to other serotonin receptors.