title: Novel brain penetrant benzofuropiperidine 5-HT₆ receptor antagonists.
abstract: 7-Arylsulfonyl substituted benzofuropiperidine was discovered as a novel scaffold for 5HT(6) receptor antagonists. Optimization by substitution at C-1 position led to identification of selective, orally bioavailable, brain penetrant antagonists with reduced hERG liability. An advanced analog tested in rat social recognition model showed significant activity suggesting potential utility in the enhancement of short-term memory.
authors.affiliation: Worldwide Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA. bsundar@cephalon.com
authors.forename: Babu G
authors.initials: BG
authors.lastname: Sundar
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Bailey
authors.forename: Derek D
authors.initials: DD
authors.lastname: Dunn
authors.forename: Edward R
authors.initials: ER
authors.lastname: Bacon
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Salvino
authors.forename: George C
authors.initials: GC
authors.lastname: Morton
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Aimone
authors.forename: Huang
authors.initials: H
authors.lastname: Zeqi
authors.forename: Joanne R
authors.initials: JR
authors.lastname: Mathiasen
authors.forename: Amy
authors.initials: A
authors.lastname: Dicamillo
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Huffman
authors.forename: Beth A
authors.initials: BA
authors.lastname: McKenna
authors.forename: Karla
authors.initials: K
authors.lastname: Kopec
authors.forename: Lily D
authors.initials: LD
authors.lastname: Lu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Brown
authors.forename: Jie
authors.initials: J
authors.lastname: Qian
authors.forename: Thelma
authors.initials: T
authors.lastname: Angeles
authors.forename: Thomas
authors.initials: T
authors.lastname: Connors
authors.forename: Chrysanthe
authors.initials: C
authors.lastname: Spais
authors.forename: Beverly
authors.initials: B
authors.lastname: Holskin
authors.forename: Deborah
authors.initials: D
authors.lastname: Galinis
authors.forename: Emir
authors.initials: E
authors.lastname: Duzic
authors.forename: Herve
authors.initials: H
authors.lastname: Schaffhauser
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Rosse
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000737:chemistry*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008570:Memory, Short-Term / Q000187:drug effects; D008956:Models, Chemical; D010880:Piperidines / Q000737:chemistry*; D051381:Rats; D011985:Receptors, Serotonin / Q000737:chemistry*; D012559:Schizophrenia / Q000188:drug therapy; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001572:Benzofurans; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor; C032727:piperidine