- Switching between agonists and antagonists at CRTh2 in a series of highly potent and selective biaryl phenoxyacetic acids.
Switching between agonists and antagonists at CRTh2 in a series of highly potent and selective biaryl phenoxyacetic acids.
Bioorganic & medicinal chemistry letters (2011-05-20)
Tim Luker, Roger Bonnert, Jerzy Schmidt, Carol Sargent, Stuart W Paine, Stephen Thom, Gary Pairaudeau, Anil Patel, Rukhsana Mohammed, Elizabeth Akam, Iain Dougall, Andrew M Davis, Phil Abbott, Steve Brough, Ian Millichip, Thomas McInally
PMID21592791
摘要
A novel series of biaryl phenoxyacetic acids was discovered as potent, selective antagonists of the chemoattractant receptor-homologous expressed on Th2 lymphocytes receptor (CRTh2 or DP2). A hit compound 4 was discovered from high throughput screening. Modulation of multiple aryl substituents afforded both agonists and antagonists, with small changes often reversing the mode of action. Understanding the complex SAR allowed design of potent antagonists such as potential candidate 34.