title: Discovery of 5-hydroxyalkyl-4-phenylpyridines as a new class of glucagon receptor antagonists.
abstract: 5-Hydroxyalkyl-4-phenylpyridines have been identified as a novel class of glucagon antagonists with potential utility for the treatment of diabetes. A lead structure with moderate activity was discovered through a high throughput screening assay. Structure-activity relationships led to the discovery of a potent antagonist, IC(50)=0.11 microM, more than 60-fold improvement over the lead structure.
authors.affiliation: Department of Chemistry Research, Bayer Research Center, 400Morgan Lane, West Haven, CT 06516, USA. gaetan.ladouceur.b@bayer.com
authors.forename: Gaetan H
authors.initials: GH
authors.lastname: Ladouceur
authors.forename: James H
authors.initials: JH
authors.lastname: Cook
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Doherty
authors.forename: William R
authors.initials: WR
authors.lastname: Schoen
authors.forename: Margit L
authors.initials: ML
authors.lastname: MacDougall
authors.forename: James N
authors.initials: JN
authors.lastname: Livingston
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D007004:Hypoglycemic Agents; D011725:Pyridines; D018027:Receptors, Glucagon