title: Acylglycinamides as inhibitors of glycine transporter type 1.
abstract: A screening hit was used as the basis for the core structure of a new series of acylglycinamide GlyT-1 inhibitors. Investigation of the SAR around four areas of diversity used facile chemistry to prepare compounds quickly. By focussing on reducing the lipophilicity and improving the aqueous solubility in the series we were able to prepare a compound (17e) with a good level of activity at GlyT-1, selectivity over GlyT-2 and moderate oral bioavailability.
authors: Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, UK. richard.blunt@xention.com
authors: Richard
authors: R
authors: Blunt
authors: Roderick
authors: R
authors: Porter
authors: Amanda
authors: A
authors: Johns
authors: David
authors: D
authors: Nash
authors: Gemma
authors: G
authors: Puckey
authors: Paul
authors: P
authors: Wyman
authors: Hugh
authors: H
authors: Herdon
authors: Simon
authors: S
authors: Teague
authors: Victoria
authors: V
authors: Hadden
authors: Stefano
authors: S
authors: Fontana
authors: Laurie
authors: L
authors: Gordon
mesh_terms: D000818:Animals; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C018556:glycine amide; D005998:Glycine