amg-853 and phenylacetic-acid

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.

Topics: Asthma; Chemistry, Pharmaceutical; Drug Design; Humans; Hypersensitivity; Inhibitory Concentration 50; Kinetics; Models, Chemical; Phenylacetates; Prostaglandin D2; Receptors, G-Protein-Coupled; Receptors, Immunologic; Receptors, Prostaglandin; Sulfonamides