title: Discovery of a novel potent GABA(B) receptor agonist.
abstract: Structure-activity studies have led to a discovery of 3-(4-pyridyl)methyl ether derivative 9d that has 25- to 50-fold greater functional potency than R-baclofen at human and rodent GABA(B) receptors in vitro. Mouse hypothermia studies confirm that this compound crosses the blood-brain barrier and is approximately 50-fold more potent after systemic administration.
authors.affiliation: XenoPort Inc., 3410 Central Expressway, Santa Clara, CA 95051, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Ge
authors.initials: G
authors.lastname: Peng
authors.forename: Thu
authors.initials: T
authors.lastname: Phan
authors.forename: Usha
authors.initials: U
authors.lastname: Dilip
authors.forename: Jian Lu
authors.initials: JL
authors.lastname: Chen
authors.forename: Tania
authors.initials: T
authors.lastname: Chernov-Rogan
authors.forename: Xuexiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Kent
authors.initials: K
authors.lastname: Grindstaff
authors.forename: Thamil
authors.initials: T
authors.lastname: Annamalai
authors.forename: Kerry
authors.initials: K
authors.lastname: Koller
authors.forename: Mark A
authors.initials: MA
authors.lastname: Gallop
authors.forename: David J
authors.initials: DJ
authors.lastname: Wustrow
mesh_terms: D000818:Animals; D001418:Baclofen / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001812:Blood-Brain Barrier; D055808:Drug Discovery; D018755:GABA Agonists / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D018080:Receptors, GABA-B / Q000187:drug effects*
chemical_list: D018755:GABA Agonists; D018080:Receptors, GABA-B; D001418:Baclofen