title: Integration of optimized substituent patterns to produce highly potent 4-aryl-pyridine glucagon receptor antagonists.
abstract: Optimized substituent patterns in 4-aryl-pyridine glucagon receptor antagonists were merged to produce highly potent derivatives containing both a 3-[(1R)-hydroxyethyl] and a 2'-hydroxy group. Due to restricted rotation of the phenyl-pyridine bond, these analogues exist as four isomers. A diastereoselective methylcopper reaction was developed to facilitate the synthesis, and single isomers were isolated with activities in the range IC(50)=10-25 nM.
authors.affiliation: Department of Chemistry Research, Bayer Research Center, 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: Donald L
authors.initials: DL
authors.lastname: Hertzog
authors.forename: J Howard
authors.initials: JH
authors.lastname: Jones
authors.forename: Thomas
authors.initials: T
authors.lastname: Hundertmark
authors.forename: Mary
authors.initials: M
authors.lastname: Korpusik
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lease
authors.forename: James N
authors.initials: JN
authors.lastname: Livingston
authors.forename: Margit L
authors.initials: ML
authors.lastname: MacDougall
authors.forename: Martin H
authors.initials: MH
authors.lastname: Osterhout
authors.forename: Kathleen
authors.initials: K
authors.lastname: Phelan
authors.forename: Romulo H
authors.initials: RH
authors.lastname: Romero
authors.forename: William R
authors.initials: WR
authors.lastname: Schoen
authors.forename: Chunning
authors.initials: C
authors.lastname: Shao
authors.forename: Roger A
authors.initials: RA
authors.lastname: Smith
mesh_terms: D001593:Benzyl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001593:Benzyl Compounds; D011725:Pyridines; D018027:Receptors, Glucagon