title: Discovery of AMG 853, a CRTH2 and DP Dual Antagonist.
abstract: Prostaglandin D2 (PGD2) plays a key role in mediating allergic reactions seen in asthma, allergic rhinitis, and atopic dermatitis. PGD2 exerts its activity through two G protein-coupled receptors (GPCRs), prostanoid D receptor (DP or DP1), and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2 or DP2). We report the optimization of a series of phenylacetic acid derivatives in an effort to improve the dual activity of AMG 009 against DP and CRTH2. These efforts led to the discovery of AMG 853 (2-(4-(4-(tert-butylcarbamoyl)-2-(2-chloro-4-cyclopropylphenyl sulfonamido)phenoxy)-5-chloro-2-fluorophenyl)acetic acid), which is being evaluated in human clinical trials for asthma.
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: An-Rong
authors.initials: AR
authors.lastname: Li
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Mike G
authors.initials: MG
authors.lastname: Johnson
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Su
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Wang
authors.initials: W
authors.lastname: Shen
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lively
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brown
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: SuJen
authors.initials: S
authors.lastname: Lai
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Felix
authors.initials: F
authors.lastname: Gonzalez Lopez De Turiso
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Qingge
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Bettina
authors.initials: B
authors.lastname: Van Lengerich
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Mike
authors.initials: M
authors.lastname: Schmitt
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Zice
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Shanna
authors.initials: S
authors.lastname: Lawlis
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Seitz
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Jay
authors.initials: J
authors.lastname: Danao
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Jill
authors.initials: J
authors.lastname: Wait
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Hua Lucy
authors.initials: HL
authors.lastname: Tang
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Grillo
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Tassie L
authors.initials: TL
authors.lastname: Collins
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Sullivan
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Medina
keywords: AMG 853; CRTH2 receptor; DP receptor; antagonist; asthma; prostaglandin D2