title: Small molecule ago-allosteric modulators of the human glucagon-like peptide-1 (hGLP-1) receptor.
abstract: Following our previous publication describing the biological profiles, we herein describe the structure-activity relationships of a core set of quinoxalines as the hGLP-1 receptor agonists. The most potent and efficacious compounds are 6,7-dichloroquinoxalines bearing an alkyl sulfonyl group at the C-2 position and a secondary alkyl amino group at the C-3 position. These findings serve as a valuable starting point for the discovery of more drug-like small molecule agonists for the hGLP-1 receptor.
authors.affiliation: Department of Medicinal Chemistry, Pfizer Global Research and Development, La Jolla, 10770 Science Center Dr., San Diego, CA 92121-1194, USA. min.teng@pfizer.com
authors.forename: Min
authors.initials: M
authors.lastname: Teng
authors.forename: Michael D
authors.initials: MD
authors.lastname: Johnson
authors.forename: Christine
authors.initials: C
authors.lastname: Thomas
authors.forename: Dan
authors.initials: D
authors.lastname: Kiel
authors.forename: James N
authors.initials: JN
authors.lastname: Lakis
authors.forename: Tim
authors.initials: T
authors.lastname: Kercher
authors.forename: Shelley
authors.initials: S
authors.lastname: Aytes
authors.forename: Jarek
authors.initials: J
authors.lastname: Kostrowicki
authors.forename: Dilip
authors.initials: D
authors.lastname: Bhumralkar
authors.forename: Larry
authors.initials: L
authors.lastname: Truesdale
authors.forename: John
authors.initials: J
authors.lastname: May
authors.forename: Ulla
authors.initials: U
authors.lastname: Sidelman
authors.forename: Janos T
authors.initials: JT
authors.lastname: Kodra
authors.forename: Anker Steen
authors.initials: AS
authors.lastname: Jørgensen
authors.forename: Preben Houlberg
authors.initials: PH
authors.lastname: Olesen
authors.forename: Johannes Cornelis
authors.initials: JC
authors.lastname: de Jong
authors.forename: Peter
authors.initials: P
authors.lastname: Madsen
authors.forename: Carsten
authors.initials: C
authors.lastname: Behrens
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pettersson
authors.forename: Lotte Bjerre
authors.initials: LB
authors.lastname: Knudsen
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Jesper
authors.initials: J
authors.lastname: Lau
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007202:Indicators and Reagents; D008968:Molecular Conformation; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000819:agonists*; D013329:Structure-Activity Relationship