title: Synthesis of cycloalkane-annelated 3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidines and their evaluation as 5-HT6 receptor antagonists.
abstract: Synthesis and biological evaluation of 1 ('angular') and 2 ('linear') cycloalkane-annelated 3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidines as novel ligands of the 5-HT(6) receptors are disclosed. The new compounds 1 and 2 are highly selective antagonists of the receptor with sub-nanomolar affinities (K(i)<1 nM). In its structure, this new chemotype lacks a basic ionizable side chain, which is considered as the characteristic feature of the 5-HT(6) receptor antagonists pharmacophore model.
authors.affiliation: Department of Organic Chemistry, Chemical Diversity Research Institute, 114401 Khimki, Moscow Region, Russia.
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Ivachtchenko
authors.forename: Dmitri E
authors.initials: DE
authors.lastname: Dmitriev
authors.forename: Elena S
authors.initials: ES
authors.lastname: Golovina
authors.forename: Elena S
authors.initials: ES
authors.lastname: Dubrovskaya
authors.forename: Madina G
authors.initials: MG
authors.lastname: Kadieva
authors.forename: Angela G
authors.initials: AG
authors.lastname: Koryakova
authors.forename: Volodymyr M
authors.initials: VM
authors.lastname: Kysil
authors.forename: Oleg D
authors.initials: OD
authors.lastname: Mitkin
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Tkachenko
authors.forename: Ilya M
authors.initials: IM
authors.lastname: Okun
authors.forename: Anton A
authors.initials: AA
authors.lastname: Vorobiov
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D011743:Pyrimidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor