Medicinal Chemistry, AstraZeneca R&D Charnwood, Loughborough, Leicestershire, UK.
Bioorg Med Chem Lett. 2011 Jun 15;21(12):3616-21. doi: 10.1016/j.bmcl.2011.04.101. Epub 2011 Apr 28.
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.
我们发现了一系列新型联苯苯氧乙酸，它们是趋化因子受体同源表达于 Th2 淋巴细胞受体（CRTh2 或 DP2）的强效、选择性拮抗剂。高内涵筛选发现了一个先导化合物 4。对多个芳基取代基进行修饰可得到激动剂和拮抗剂，小的结构变化往往会改变作用模式。对复杂的 SAR 的理解使得设计出了强效拮抗剂，如潜在候选化合物 34。
