title: Synthesis, in vitro binding profile, and central nervous system penetrability of the highly potent 5-HT3 receptor antagonist [3H]-4-(2-methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole.
abstract: 4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with this radioligand indicate that it effectively penetrates the blood-brain barrier upon peripheral administration. Thus, 5 should be a useful pharmacological tool for both in vitro and in vivo studies of this class of compounds.
authors.affiliation: Pfizer Central Research, Department of Medicinal Chemistry, Groton, Connecticut 06340.
authors.forename: T
authors.initials: T
authors.lastname: Rosen
authors.forename: T F
authors.initials: TF
authors.lastname: Seeger
authors.forename: S
authors.initials: S
authors.lastname: McLean
authors.forename: A A
authors.initials: AA
authors.lastname: Nagel
authors.forename: J L
authors.initials: JL
authors.lastname: Ives
authors.forename: K J
authors.initials: KJ
authors.lastname: Guarino
authors.forename: D
authors.initials: D
authors.lastname: Bryce
authors.forename: J
authors.initials: J
authors.lastname: Furman
authors.forename: R W
authors.initials: RW
authors.lastname: Roth
authors.forename: P M
authors.initials: PM
authors.lastname: Chalabi
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D005910:Glioma / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D015394:Molecular Structure; D009447:Neuroblastoma / Q000378:metabolism; D012702:Serotonin Antagonists; D013844:Thiazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
chemical_list: D007093:Imidazoles; D012702:Serotonin Antagonists; D013844:Thiazoles; C066281:4-(2-methoxyphenyl)-2-(4(5)-methyl-5(4)-imidazolylmethyl)thiazole