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ID: ALA1140777

Journal: Bioorg Med Chem Lett

Title: 3,4-Diamino-2,5-thiadiazole-1-oxides as potent CXCR2/CXCR1 antagonists.

Authors: Biju P, Taveras A, Yu Y, Zheng J, Chao J, Rindgen D, Jakway J, Hipkin RW, Fossetta J, Fan X, Fine J, Qiu H, Merritt JR, Baldwin JJ.

Abstract: A series of novel and potent 3,4-diamino-2,5-thiadiazole-1-oxides were prepared and found to show excellent binding affinities for CXCR2 and CXCR1 receptors and excellent inhibitory activity of Gro-alpha and IL-8 mediated in vitro hPMN MPO release of CXCR2 and CXCR1 expressing cell lines. On the other hand, a closely related 3,4-diamino-2,5-thiadiazole-dioxide did not show functional activity despite its excellent binding affinities for CXCR2 and CXCR1 in membrane binding assays. A detailed SAR has been discussed in these two closely related structures.

CiteXplore: 18006311

DOI: 10.1016/j.bmcl.2007.10.094