title: Discovery and optimization of CRTH2 and DP dual antagonists.
abstract: A series of phenylacetic acid derivatives was discovered as CRTH2 antagonists. Modification of the series led to compounds that are also antagonists of DP. Since activation of CRTH2 and DP are believed to play key roles in mediating responses of asthma and other immune diseases, this series was optimized to increase the dual antagonistic activities and improve pharmacokinetic properties. These efforts led to selection of AMG 009 as a clinical candidate.
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. jiwenl@amgen.com
authors.forename: Jiwen
authors.initials: J
authors.lastname: Liu
authors.forename: Zice
authors.initials: Z
authors.lastname: Fu
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Wang
authors.forename: Mike
authors.initials: M
authors.lastname: Schmitt
authors.forename: Alan
authors.initials: A
authors.lastname: Huang
authors.forename: Derek
authors.initials: D
authors.lastname: Marshall
authors.forename: George
authors.initials: G
authors.lastname: Tonn
authors.forename: Lisa
authors.initials: L
authors.lastname: Seitz
authors.forename: Tim
authors.initials: T
authors.lastname: Sullivan
authors.forename: H
authors.initials: H
authors.lastname: Lucy Tang
authors.forename: Tassie
authors.initials: T
authors.lastname: Collins
authors.forename: Julio
authors.initials: J
authors.lastname: Medina
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D011982:Receptors, Prostaglandin / Q000737:chemistry* / Q000145:classification; D013329:Structure-Activity Relationship; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D011982:Receptors, Prostaglandin