title: Chromenones as potent bradykinin B1 antagonists.
abstract: A series of fused 6,6-bicyclic chromenones was investigated for activity against the bradykinin B1 receptor. SAR studies based on a pharmacophore model revealed compounds with high affinity for both human and rabbit B1. These compounds demonstrated favorable pharmacokinetic properties and 5-chlorochromenone 15 was efficacious in a carrageenan-induced mechanical hyperalgesia model for chronic pain.
authors.affiliation: Department of Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
authors.forename: Marian C
authors.initials: MC
authors.lastname: Bryan
authors.forename: Kaustav
authors.initials: K
authors.lastname: Biswas
authors.forename: Tanya A N
authors.initials: TA
authors.lastname: Peterkin
authors.forename: Robert M
authors.initials: RM
authors.lastname: Rzasa
authors.forename: Leyla
authors.initials: L
authors.lastname: Arik
authors.forename: Sonya G
authors.initials: SG
authors.lastname: Lehto
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Feng-Yin
authors.initials: FY
authors.lastname: Hsieh
authors.forename: Cen
authors.initials: C
authors.lastname: Xu
authors.forename: Robert T
authors.initials: RT
authors.lastname: Fremeau
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Allen
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D002351:Carrageenan / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D059350:Chronic Pain / Q000188:drug therapy; D015195:Drug Design; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D011817:Rabbits; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C573893:5-chlorochromenone; D001578:Benzopyrans; D065169:Bradykinin B1 Receptor Antagonists; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan