title: Synthesis and biological study of 3-(phenylsulfonyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines as potent and selective serotonin 5-HT6 receptor antagonists.
abstract: A number of 3-(phenylsulfonyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines were prepared and their 5-HT6 receptor binding affinity and ability to inhibit the functional cellular responses to serotonin were evaluated. 3-[(3-chlorophenyl)sulfonyl]-N-(tetrahydrofuran-2-ylmethyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5-amine 2{5,26} appeared to be the most active in a functional assay (IC50=29.0 nM) and 3-(phenylsulfonyl)-N-(2-thienylmethyl) thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5-amine 2{1,28} demonstrated the greatest affinity in a 5-HT6 receptor radioligand binding assay (Ki=1.7 nM). A screening of 5-HT2A and 5-HT2B receptor affinity revealed that 3-(phenylsulfonyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines are highly selective 5-HT6 receptor ligands.
authors.affiliation: Chemical Diversity Research Institute, 114401 Khimki, Moscow Reg, 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; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D011743:Pyrimidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014230:Triazoles; C097216:serotonin 6 receptor