title: Optimization of phenylacetic acid derivatives for balanced CRTH2 and DP dual antagonists.
abstract: Our first generation CRTH2 and DP dual antagonists, represented by AMG 009, are more potent toward the CRTH2 receptor than to the DP receptor. Here we report our efforts in the discovery of CRTH2 and DP dual antagonists with more balanced potencies to both receptors, such as compound 15.
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. jiwenl@amgen.com
authors.forename: Jiwen Jim
authors.initials: JJ
authors.lastname: Liu
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Wang
authors.forename: Michael G
authors.initials: MG
authors.lastname: Johnson
authors.forename: An-Rong
authors.initials: AR
authors.lastname: Li
authors.forename: Wang
authors.initials: W
authors.lastname: Shen
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Yongli
authors.initials: Y
authors.lastname: Su
authors.forename: Matthew
authors.initials: M
authors.lastname: Brown
authors.forename: Bettina
authors.initials: B
authors.lastname: Van Lengerich
authors.forename: Erika
authors.initials: E
authors.lastname: Rickel
authors.forename: Tod
authors.initials: T
authors.lastname: Martin
authors.forename: Alison
authors.initials: A
authors.lastname: Budelsky
authors.forename: Lisa
authors.initials: L
authors.lastname: Seitz
authors.forename: Jay
authors.initials: J
authors.lastname: Danao
authors.forename: H Lucy
authors.initials: HL
authors.lastname: Tang
authors.forename: Tassie
authors.initials: T
authors.lastname: Collins
authors.forename: Julio C
authors.initials: JC
authors.lastname: Medina
mesh_terms: D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*
chemical_list: D010648:Phenylacetates; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C501562:prostanoid D receptor 1, human; C025136:phenylacetic acid; C036293:prostaglandin D2 receptor