- Synthesis and structure-activity relationship of 2-amino-3-heteroaryl-quinoxalines as non-peptide, small-molecule antagonists for interleukin-8 receptor
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Interleukin-8 modulation is implicated in many inflammatory and cancer diseases. Starting from a mass-screening hit, the synthesis and structure-activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule interleukine-8 receptor antagonists have been developed. The optimized derivatives, PD 0210293 (13y) and PD 0220245 (13r), show inhibition of both IL-8 receptor binding and IL-8-mediated neutrophil chemotaxis.
- Li, Jie Jack,Carson, Kenneth G.,Trivedi, Bharat K.,Yue, Wen Song,Ye, Qing,Glynn, Roberta A.,Miller, Steven R.,Connor, David T.,Roth, Bruce D.,Luly, Jay R.,Low, Joseph E.,Heilig, David J.,Yang, Weixing,Qin, Shixin,Hunt, Stephen
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p. 3777 - 3790
(2007/10/03)
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- Substituted quinoxaline derivatives as interleukin-8 receptor antagonists
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Quinoxaline compounds are described as well as methods for the preparation and pharmaceutical compositions of same, which are useful as interleukin-8 (IL-8) receptor antagonists and can be used in the treatment of a chemokine-mediated disease wherein the chemokine binds to an IL-8a (CXCR1) or b (CXCR2) receptor such as a chemokine-mediated disease selected from psoriasis, or atopic distress syndrome, arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, gastric ulcer, septic shock, endotoxic shock, gram-negative sepsis, toxic shock syndrome, stroke, cardiac and renal reperfusion injury, glomerulo-nephritis, or thrombosis, Alzheimer's disease, graft versus host reaction, allograft rejections, or allergic diseases.
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