Merritt J Robert, Rokosz Laura L, Nelson Kingsley H, Kaiser Bernd, Wang Wei, Stauffer Tara M, Ozgur Lynne E, Schilling Adriane, Li Ge, Baldwin John J, Taveras Arthur G, Dwyer Michael P, Chao Jianping
Pharmacopeia Drug Discovery, Inc., 3000 Eastpark Blvd., Cranbury, NJ 08512, USA.
Bioorg Med Chem Lett. 2006 Aug 1;16(15):4107-10. doi: 10.1016/j.bmcl.2006.04.082. Epub 2006 May 11.
A novel series of 3,4-diaminocyclobut-3-ene-1,2-diones was prepared and found to show potent inhibitory activity of CXCR2 binding and IL-8-mediated chemotaxis of a CXCR2-expressing cell line. Microsome stability and Caco2 studies were subsequently used to show that compounds of this chemotype are predicted to have good oral bioavailability and are thus suitable for pharmaceutical development.
制备了一系列新型的3,4-二氨基环丁-3-烯-1,2-二酮，并发现它们对CXCR2结合以及CXCR2表达细胞系的IL-8介导趋化作用具有强效抑制活性。随后通过微粒体稳定性和Caco2研究表明，这种化学类型的化合物预计具有良好的口服生物利用度，因此适合用于药物开发。
