title: Novel CGRP receptor antagonists from central amide replacements causing a reversal of preferred chirality.
abstract: A previously utilized quinoline-for-N-phenylamide replacement strategy was employed against a central amide in a novel class of CGRP receptor antagonists. A unique and unexpected substitution pattern was ultimately required to maintain reasonable affinity for the CGRP receptor, while at the same time predicting acceptable heterocycle positioning for related analogs. Subsequently, specific quinoline and naphthyridine compounds were prepared which supported these structural predictions by displaying CGRP binding affinities in the 0.037-0.15 nM range.
authors.affiliation: Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 4, 770 Sumneytown Pike, West Point, PA 19486, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wood
authors.forename: Kathy M
authors.initials: KM
authors.lastname: Schirripa
authors.forename: June J
authors.initials: JJ
authors.lastname: Kim
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Bednar
authors.forename: John F
authors.initials: JF
authors.lastname: Fay
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Bruno
authors.forename: Eric L
authors.initials: EL
authors.lastname: Moore
authors.forename: Scott D
authors.initials: SD
authors.lastname: Mosser
authors.forename: Shane
authors.initials: S
authors.lastname: Roller
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Salvatore
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacca
authors.forename: Harold G
authors.initials: HG
authors.lastname: Selnick
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D013237:Stereoisomerism
chemical_list: D000577:Amides; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists