Abstract:
: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.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Cesarini S,Spallarossa A,Ranise A,Bruno O,Arduino N,Bertolotto M,Dallegri F,Tognolini M,Gobbetti T,Barocelli Edoi
10.1016/j.bmc.2009.04.006subject
Has Abstractpub_date
2009-05-15 00:00:00pages
3580-7issue
10eissn
0968-0896issn
1464-3391pii
S0968-0896(09)00346-0journal_volume
17pub_type
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