251. Optimization of phenylacetic acid derivatives for CRTH2 and DP selective antagonism.
- Author
-
Wang Y, Fu Z, Schmitt M, Wang X, Shen W, Rickel E, Martin T, Budelsky A, Marshall D, Collins T, Tang HL, Medina JC, and Liu JJ
- Subjects
- Asthma therapy, Chemistry, Pharmaceutical methods, Drug Design, Humans, Hypersensitivity drug therapy, Inhibitory Concentration 50, Kinetics, Models, Chemical, Phenylacetates chemistry, Phenylacetates pharmacology, Prostaglandin D2 metabolism, Receptors, G-Protein-Coupled metabolism, Sulfonamides chemistry, Sulfonamides pharmacology, Receptors, Immunologic antagonists & inhibitors, Receptors, Prostaglandin antagonists & inhibitors
- 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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF