Discovery of 5-hydroxyalkyl-4-phenylpyridines as a new class of glucagon receptor antagonists.
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.
Ladouceur
Gaetan H
GH
Department of Chemistry Research, Bayer Research Center, 400Morgan Lane, West Haven, CT 06516, USA. gaetan.ladouceur.b@bayer.com
Cook
James H
JH
Doherty
Elizabeth M
EM
Schoen
William R
WR
MacDougall
Margit L
ML
Livingston
James N
JN
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
D007004:Hypoglycemic Agents; D011725:Pyridines; D018027:Receptors, Glucagon