Cesarini, Sara and Spallarossa, Andrea and Ranise, Angelo and Bruno, Olga and Arduino, Nicoletta and Bertolotto, Maria and Dallegri, Franco and Tognolini, Massimiliano and Gobbetti, Thomas and Barocelli, Elisabetta (2009) 6-Amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives as a new class of potent inhibitors of Interleukin-8-induced neutrophil chemotaxis. Bioorganic & Medicinal Chemistry, 17 (10). 3580 - 3587.
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Official URL: http://www.sciencedirect.com/science/article/B6TF8...
A series of 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives was synthesized. The compounds demonstrated to be novel, potent and selective inhibitors of Interleukin-8-induced human neutrophil chemotaxis. A SAR study was performed by varying the carbonyl function at position 5 and the chain linked to the amino group at position 6 of the scaffold. All the compounds of the series displayed inhibitory activity at nano- or picomolar concentrations against Interleukin-8-driven migration and no activity against fMLP- and C5a-induced chemotaxis. The binding tests of selected compounds on CXCR1 and CXCR2 receptors were negative. The most potent derivative showed in vivo efficacy in a mouse model of Zymosan-induced peritonitis.
|Uncontrolled Keywords:||eutrophil; Chemotaxis; Interleukin-8; Inhibitors; Peritonitis|
|Subjects:||Biomedical Science > Nanomedicine|
|Deposited On:||04 Aug 2009 10:39|
|Last Modified:||04 Aug 2009 10:39|
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