title: Phenyl benzenesulfonamides are novel and selective 5-HT6 antagonists: identification of N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134).
abstract: Substituted N-phenyl-4-methoxy-3-piperazin-1-ylbenzenesulfonamides and conformationally restricted analogues have been identified as high affinity and selective 5-HT6 antagonists. Compounds from this series had a range of pharmacokinetic profiles in rat and in general there was a correlation between clearance and CNS penetration. Based on its overall biological profile 2 (SB-357134) was selected for further pre-clinical evaluation.
authors.affiliation: Discovery Chemistry Europe, SmithKline Beecham Pharmaceuticals, Discovery Research, Harlow, Essex, UK. steve_bromidge-1@sbphrd.com
authors.forename: S M
authors.initials: SM
authors.lastname: Bromidge
authors.forename: S E
authors.initials: SE
authors.lastname: Clarke
authors.forename: T
authors.initials: T
authors.lastname: Gager
authors.forename: K
authors.initials: K
authors.lastname: Griffith
authors.forename: P
authors.initials: P
authors.lastname: Jeffrey
authors.forename: A J
authors.initials: AJ
authors.lastname: Jennings
authors.forename: G F
authors.initials: GF
authors.lastname: Joiner
authors.forename: F D
authors.initials: FD
authors.lastname: King
authors.forename: P J
authors.initials: PJ
authors.lastname: Lovell
authors.forename: S F
authors.initials: SF
authors.lastname: Moss
authors.forename: H
authors.initials: H
authors.lastname: Newman
authors.forename: G
authors.initials: G
authors.lastname: Riley
authors.forename: D
authors.initials: D
authors.lastname: Rogers
authors.forename: C
authors.initials: C
authors.lastname: Routledge
authors.forename: H
authors.initials: H
authors.lastname: Serafinowska
authors.forename: D R
authors.initials: DR
authors.lastname: Smith
mesh_terms: D000818:Animals; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; C422502:N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide; D000096926:Benzenesulfonamides; C097216:serotonin 6 receptor