title: Synthesis and structure-activity relationships of 3-phenyl-2-propenamides as inhibitors of glycogen phosphorylase a.
abstract: A series of 3-phenyl-2-propenamides discovered from a high-throughput screening campaign as novel, potent, glucose-sensitive inhibitors of human liver glycogen phosphorylase a is described. A solid-phase synthesis on DMHB resin was also developed which provided efficient access not only to certain analogues that could not be cleanly made using more traditional means, but also to a variety of additional analogues. The SAR scope and synthetic strategy are presented herein.
authors.affiliation: Discovery Research, GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA 19426-0989, USA.
authors.forename: Yue H
authors.initials: YH
authors.lastname: Li
authors.forename: Frank T
authors.initials: FT
authors.lastname: Coppo
authors.forename: Karen A
authors.initials: KA
authors.lastname: Evans
authors.forename: Todd L
authors.initials: TL
authors.lastname: Graybill
authors.forename: Mehul
authors.initials: M
authors.lastname: Patel
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gale
authors.forename: Hu
authors.initials: H
authors.lastname: Li
authors.forename: Francis
authors.initials: F
authors.lastname: Tavares
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Thomson
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors*; D006801:Humans; D008099:Liver / Q000201:enzymology; D012117:Resins, Synthetic / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000178:Acrylamides; D004791:Enzyme Inhibitors; D012117:Resins, Synthetic; D024981:Glycogen Phosphorylase