Design, synthesis, and evaluation of novel 3-amino-4-hydrazine-cyclobut-3-ene-1, 2-diones as potent and selective CXCR2 chemokine receptor antagonists

…, N Sawyer, FG Gervais, M Henault, S Kargman…

Index: Liu, Shilan; Liu, Yinhui; Wang, Hongmei; Ding, YiLi; Wu, Hao; Dong, Jingchao; Wong, Angela; Chen, Shu-Hui; Li, Ge; Chan, Manuel; Sawyer, Nicole; Gervais, Francois G.; Henault, Martin; Kargman, Stacia; Bedard, Leanne L.; Han, Yongxin; Friesen, Rick; Lobell, Robert B.; Stout, David M. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 19 p. 5741 - 5745

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Citation Number: 7

Abstract

We describe herein a novel series of 3-amino-4-hydrazine-cyclobut-3-ene-1, 2-diones as potent and selective inhibitors against the CXCR2 chemokine receptor and IL-8-mediated chemotaxis of a CXCR2-expressing cell line. Furthermore, these alkyl-hydrazine series inhibitors such as 5b demonstrated acceptable metabolic stability when incubated in human and rat microsomes.