title: Novel 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines are potent 5-HT(6) agonists.
abstract: A series of 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines 10a-z was prepared as novel 5-HT(6) ligands. The best compounds were high affinity, full agonists at 5-HT(6) receptors. Several agonists demonstrated good selectivity over other serotonergic and dopaminergic receptors. Acute administration of selective agonist 10e significantly increased extracellular GABA concentrations in rat frontal cortex. This compound also reduced adjunctive drinking behavior in the rat schedule-induced polydipsia assay, possibly predictive of efficacy in obsessive compulsive disorder and other anxiety related disorders.
authors.affiliation: Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. bernotr@wyeth.com
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Bernotas
authors.forename: Steven
authors.initials: S
authors.lastname: Lenicek
authors.forename: Schuyler
authors.initials: S
authors.lastname: Antane
authors.forename: Derek C
authors.initials: DC
authors.lastname: Cole
authors.forename: Boyd L
authors.initials: BL
authors.lastname: Harrison
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Robichaud
authors.forename: Guo Ming
authors.initials: GM
authors.lastname: Zhang
authors.forename: Deborah
authors.initials: D
authors.lastname: Smith
authors.forename: Brian
authors.initials: B
authors.lastname: Platt
authors.forename: Qian
authors.initials: Q
authors.lastname: Lin
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Joseph
authors.initials: J
authors.lastname: Coupet
authors.forename: Sharon
authors.initials: S
authors.lastname: Rosenzweig-Lipson
authors.forename: Chad E
authors.initials: CE
authors.lastname: Beyer
authors.forename: Lee E
authors.initials: LE
authors.lastname: Schechter
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004327:Drinking Behavior / Q000187:drug effects*; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism
chemical_list: D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C097216:serotonin 6 receptor; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid