title: 5-Cyclic amine-3-arylsulfonylindazoles as novel 5-HT6 receptor antagonists.
abstract: Novel 5-cyclic amine-3-arylsulfonylindazoles were prepared, and several analogues within this class have been identified as high-affinity 5-HT(6) receptor ligands with improved pharmacokinetic and pharmacological properties. One selected example, 18b, showed good brain penetrability and a generally favorable pharmacokinetic profile with procognitive efficacy in the rat novel object recognition assay. The synthesis and structure-activity relationship of this potent class are discussed.
authors.affiliation: Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA. Haydars@wyeth.com
authors.forename: Simon N
authors.initials: SN
authors.lastname: Haydar
authors.forename: Heedong
authors.initials: H
authors.lastname: Yun
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Andrae
authors.forename: James
authors.initials: J
authors.lastname: Mattes
authors.forename: Jean
authors.initials: J
authors.lastname: Zhang
authors.forename: Angela
authors.initials: A
authors.lastname: Kramer
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Smith
authors.forename: Christine
authors.initials: C
authors.lastname: Huselton
authors.forename: Radka
authors.initials: R
authors.lastname: Graf
authors.forename: Suzan
authors.initials: S
authors.lastname: Aschmies
authors.forename: Lee E
authors.initials: LE
authors.lastname: Schechter
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Comery
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Robichaud
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006801:Humans; D007191:Indazoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008956:Models, Chemical; D015394:Molecular Structure; D051381:Rats; D044403:Receptor, Serotonin, 5-HT2B / Q000737:chemistry / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D007191:Indazoles; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D013450:Sulfones; C097216:serotonin 6 receptor