title: Optimization of phenylacetic acid derivatives for CRTH2 and DP selective antagonism.
abstract: We have previously reported that optimization of a series of phenylacetic acid derivatives led to the discovery of CRTH2 and DP dual antagonists, such as AMG 009 and AMG 853. During the optimization process, we discovered that minor structural modifications also afforded potent and selective CRTH2 or DP antagonists. Here we report the structure-activity relationship that led to the discovery of selective CRTH2 antagonists such as 2 and 17, and selective DP antagonists, such as 4 and 5.
authors: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Yingcai
authors: Y
authors: Wang
authors: Zice
authors: Z
authors: Fu
authors: Michael
authors: M
authors: Schmitt
authors: Xuemei
authors: X
authors: Wang
authors: Wang
authors: W
authors: Shen
authors: Erika
authors: E
authors: Rickel
authors: Tod
authors: T
authors: Martin
authors: Alison
authors: A
authors: Budelsky
authors: Derek
authors: D
authors: Marshall
authors: Tassie
authors: T
authors: Collins
authors: H Lucy
authors: HL
authors: Tang
authors: Julio C
authors: JC
authors: Medina
authors: Jiwen Jim
authors: JJ
authors: Liu
mesh_terms: D001249:Asthma / Q000628:therapy; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D010648:Phenylacetates / Q000737:chemistry / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology
chemical_list: C570879:AMG 009; D010648:Phenylacetates; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; C573852:vidupiprant; C025136:phenylacetic acid; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor