891658-02-9Relevant academic research and scientific papers
Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2
Moriconi, Alessio,Cesta, Maria Candida,Cervellera, Maria Neve,Aramini, Andrea,Coniglio, Silvia,Colagioia, Sandro,Beccari, Andrea Rosario,Bizzarri, Cinzia,Cavicchia, Michela Rita,Locati, Massimo,Galliera, Emanuela,Di Benedetto, Paola,Vigilante, Paolo,Bertini, Riccardo,Allegretti, Marcello
, p. 3984 - 4002 (2008/02/11)
Chemokines CXCL8 and CXCL1 play a key role in the recruitment of neutrophils at the site of inflammation. CXCL8 binds two membrane receptors, CXCR1 and CXCR2, whereas CXCL1 is a selective agonist for CXCR2. In the past decade, the physiopathological role of CXCL8 and CXCL1 has been investigated. A novel class of small molecular weight allosteric CXCR1 inhibitors was identified, and reparixin, the first drug candidate, is currently under clinical investigation in the prevention of ischemia/reperfusion injury in organ transplantation. Reparixin binding mode to CXCR1 has been studied and used for a computer-assisted design program of dual allosteric CXCR1 and CXCR2 inhibitors. In this paper, the results of modeling-driven SAR studies for the identification of potent dual inhibitors are discussed, and three new compounds (56, 67, and 79) sharing a common triflate moiety have been selected as potential leads with optimized pharmacokinetic characteristics.
2-ARYLPROPIONIC ACID DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Page/Page column 17-18, (2008/06/13)
The present invention relates to selected (R)-2-phenyl-propionamides and (R)-2-phenyl-sulfonamides with a hydrogen bond acceptor atom/group in a well defined position in the chemical space. These compounds show a surprising potent inhibitory effect on C5a induced human PMN chemotaxis. The compounds of the invention absolutely lack of CXCL8 inhibitory activity. Said compounds are useful in the treatment of pathologies depending on the chemotactic activation of neutrophils and monocytes induced by the fraction C5a of the complement. In particular, the compounds of the invention are useful in the treatment of sepsis, psoriasis, rheumatoid arthritis, ulcerative colitis, acute respiratory distress syndrome, idiopathic fibrosis, glomerulonephritis and in the prevention and treatment of injury caused by ischemia and reperfusion.
