title: Discovery of N1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine as a potent, selective, and orally active 5-HT(6) receptor agonist.
abstract: N1-Arylsulfonyltryptamines have been identified as 5-HT6 receptor ligands. In particular, N1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine (11q) is a high affinity, potent full agonist (5-HT6 Ki = 2 nM, EC50 = 6.5 nM, Emax = 95.5%). Compound 11q is selective in a panel of over 40 receptors and ion channels, has good pharmacokinetic profile, has been shown to increase GABA levels in the rat frontal cortex, and is active in the schedule-induced polydipsia model for obsessive compulsive disorders.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, New York 10965, USA. coledc@wyeth.com
authors.forename: Derek C
authors.initials: DC
authors.lastname: Cole
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Stock
authors.forename: William J
authors.initials: WJ
authors.lastname: Lennox
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Bernotas
authors.forename: John W
authors.initials: JW
authors.lastname: Ellingboe
authors.forename: Steve
authors.initials: S
authors.lastname: Boikess
authors.forename: Joseph
authors.initials: J
authors.lastname: Coupet
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Smith
authors.forename: Louis
authors.initials: L
authors.lastname: Leung
authors.forename: Guo-Ming
authors.initials: GM
authors.lastname: Zhang
authors.forename: Xidong
authors.initials: X
authors.lastname: Feng
authors.forename: Michael F
authors.initials: MF
authors.lastname: Kelly
authors.forename: Rocco
authors.initials: R
authors.lastname: Galante
authors.forename: Pingzhong
authors.initials: P
authors.lastname: Huang
authors.forename: Lee A
authors.initials: LA
authors.lastname: Dawson
authors.forename: Karen
authors.initials: K
authors.lastname: Marquis
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: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D005625:Frontal Lobe / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D017551:Microdialysis; D008862:Microsomes, Liver / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D014363:Tryptamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C525454:N(1)-(6-chloroimidazo(2,1-b)(1,3)thiazole-5-sulfonyl)tryptamine; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; D014363:Tryptamines; C097216:serotonin 6 receptor; D005680:gamma-Aminobutyric Acid