title: 5-Chloroindoloyl glycine amide inhibitors of glycogen phosphorylase: synthesis, in vitro, in vivo, and X-ray crystallographic characterization.
abstract: The synthesis, in vitro, and in vivo biological characterization of a series of achiral 5-chloroindoloyl glycine amide inhibitors of human liver glycogen phosphorylase A are described. Improved potency over previously reported compounds in cellular and in vivo assays was observed. The allosteric binding site of these compounds was shown by X-ray crystallography to be the same as that reported previously for 5-chloroindoloyl norstatine amides.
authors.affiliation: Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. stephen_w_wright@groton.pfizer.com
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wright
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Rath
authors.forename: Paul E
authors.initials: PE
authors.lastname: Genereux
authors.forename: David L
authors.initials: DL
authors.lastname: Hageman
authors.forename: Carolyn B
authors.initials: CB
authors.lastname: Levy
authors.forename: Lester D
authors.initials: LD
authors.lastname: McClure
authors.forename: Scott C
authors.initials: SC
authors.lastname: McCoid
authors.forename: R Kirk
authors.initials: RK
authors.lastname: McPherson
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Schelhorn
authors.forename: Donald E
authors.initials: DE
authors.lastname: Wilder
authors.forename: William J
authors.initials: WJ
authors.lastname: Zavadoski
authors.forename: E Michael
authors.initials: EM
authors.lastname: Gibbs
authors.forename: Judith L
authors.initials: JL
authors.lastname: Treadway
mesh_terms: D000495:Allosteric Site; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000614:Aminocaproates / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005998:Glycine / Q000737:chemistry / Q000494:pharmacology; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000201:enzymology / Q000378:metabolism
chemical_list: C501381:5-chloroindoloyl glycine amide; D000577:Amides; D000614:Aminocaproates; D004791:Enzyme Inhibitors; D007211:Indoles; C034495:3-amino-2-hydroxy-5-methylhexanoic acid; D024981:Glycogen Phosphorylase; D005998:Glycine