title: Solution phase parallel synthesis of substituted 3-phenylsulfonyl-[1,2,3]triazolo[1,5-a]quinazolines: selective serotonin 5-HT(6) receptor antagonists.
abstract: 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-HT(6)R antagonists. The most active 5-HT(6)R antagonists have IC(50) <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.
authors.affiliation: Chemical Diversity Research Institute, Russia.
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Ivachtchenko
authors.forename: Elena S
authors.initials: ES
authors.lastname: Golovina
authors.forename: Madina G
authors.initials: MG
authors.lastname: Kadieva
authors.forename: Angela G
authors.initials: AG
authors.lastname: Koryakova
authors.forename: Sergiy M
authors.initials: SM
authors.lastname: Kovalenko
authors.forename: Oleg D
authors.initials: OD
authors.lastname: Mitkin
authors.forename: Ilya M
authors.initials: IM
authors.lastname: Okun
authors.forename: Irina M
authors.initials: IM
authors.lastname: Ravnyeyko
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Tkachenko
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Zaremba
mesh_terms: D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000737:chemistry*; D054852:Small Molecule Libraries; D012996:Solutions; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D011799:Quinazolines; D011985:Receptors, Serotonin; D054852:Small Molecule Libraries; D012996:Solutions; C097216:serotonin 6 receptor