新型含二取代苯基的3,4-二氨基-3-环丁烯-1,2-二酮作为CXCR2受体拮抗剂的合成及构效关系
Synthesis and structure-activity relationships of new disubstituted phenyl-containing 3,4-diamino-3-cyclobutene-1,2-diones as CXCR2 receptor antagonists.
作者信息
Lai Gaifa, Merritt J Robert, He Zhenmin, Feng Daming, Chao Jianhua, Czarniecki Michael F, Rokosz Laura L, Stauffer Tara M, Rindgen Diane, Taveras Arthur G
机构信息
Pharmacopeia, Inc., 3000 Eastpark Boulevard, Cranbury, NJ 08512, USA.
出版信息
Bioorg Med Chem Lett. 2008 Mar 15;18(6):1864-8. doi: 10.1016/j.bmcl.2008.02.010. Epub 2008 Feb 10.
A series of 3,4- and 3,5-disubstituted phenyl-containing cyclobutenedione analogues were synthesized and evaluated as CXCR2 receptor antagonists. Variations in the disubstitution pattern of the phenyl ring afforded new compounds with potent CXCR2 binding affinity in the low nanomolar ranges. Moreover, two potent compounds 19 and 26 exhibited good oral pharmacokinetic profiles.
合成了一系列含3,4-和3,5-二取代苯基的环丁烯二酮类似物，并将其作为CXCR2受体拮抗剂进行评估。苯环二取代模式的变化产生了在低纳摩尔范围内具有强效CXCR2结合亲和力的新化合物。此外，两种强效化合物19和26表现出良好的口服药代动力学特征。
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