title: Discovery and investigation of a novel class of thiophene-derived antagonists of the human glucagon receptor.
abstract: A novel class of antagonists of the human glucagon receptor (hGCGR) has been discovered. Systematic modification of the lead compound identified substituents that were essential for activity and those that were amenable to further optimization. This SAR exploration resulted in the synthesis of 13, which exhibited good potency as an hGCGR functional antagonist (IC50 = 34 nM) and moderate bioavailability (36% in mice).
authors.affiliation: Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. joseph_duffy@merck.com
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Duffy
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kirk
authors.forename: Zenon
authors.initials: Z
authors.lastname: Konteatis
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Campbell
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Brady
authors.forename: Mari Rios
authors.initials: MR
authors.lastname: Candelore
authors.forename: Victor D H
authors.initials: VD
authors.lastname: Ding
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Jiang
authors.forename: Frank
authors.initials: F
authors.lastname: Liu
authors.forename: Sajjad A
authors.initials: SA
authors.lastname: Qureshi
authors.forename: Richard
authors.initials: R
authors.lastname: Saperstein
authors.forename: Deborah
authors.initials: D
authors.lastname: Szalkowski
authors.forename: Sharon
authors.initials: S
authors.lastname: Tong
authors.forename: Lauri M
authors.initials: LM
authors.lastname: Tota
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Yang
authors.forename: Peter
authors.initials: P
authors.lastname: Zafian
authors.forename: Song
authors.initials: S
authors.lastname: Zheng
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Chapman
authors.forename: Bei B
authors.initials: BB
authors.lastname: Zhang
authors.forename: James R
authors.initials: JR
authors.lastname: Tata
mesh_terms: D006801:Humans; D015394:Molecular Structure; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology*
chemical_list: D018027:Receptors, Glucagon; D013876:Thiophenes