title: SB-656104-A: a novel 5-HT(7) receptor antagonist with improved in vivo properties.
abstract: A focused SAR study around the previously reported selective 5-HT(7) receptor antagonist, SB-269970-A has resulted in the identification of a structurally related analogue having an improved pharmacokinetic profile. Replacement of the phenolic group in SB-269970-A with an indole moiety, and replacement of the piperidinyl 4-methyl group with a heterocyclic ring system proved to be the key changes leading to the identification of SB-656104-A.
authors.affiliation: GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK. ian_t_forbes@gsk.com
authors.forename: Ian T
authors.initials: IT
authors.lastname: Forbes
authors.forename: Sara
authors.initials: S
authors.lastname: Douglas
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Gribble
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ife
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lightfoot
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Garner
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Riley
authors.forename: Phillip
authors.initials: P
authors.lastname: Jeffrey
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stevens
authors.forename: Tania O
authors.initials: TO
authors.lastname: Stean
authors.forename: David R
authors.initials: DR
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D006571:Heterocyclic Compounds; D007211:Indoles; D010636:Phenols / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D011485:Protein Binding; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000737:chemistry*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000493:pharmacokinetics
chemical_list: D006571:Heterocyclic Compounds; D007211:Indoles; D010636:Phenols; D011759:Pyrrolidines; D011985:Receptors, Serotonin; C404922:SB 269970; C475591:SB-656104-A; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor