83394-44-9Relevant articles and documents
NSAIDs do not require the presence of a carboxylic acid to exert their anti-inflammatory effect – why do we keep using it?
Ullah, Nasir,Huang, Zhangjian,Sanaee, Forough,Rodriguez-Dimitrescu, Alexandra,Aldawsari, Fahad,Jamali, Fakhreddin,Bhardwaj, Atul,Islam, Nazar Ul,Velázquez-Martínez, Carlos A.
, p. 1018 - 1028 (2016/10/09)
The carboxylic acid group (–COOH) present in classical NSAIDs is partly responsible for the gastric toxicity associated with the administration of these drugs. This concept has been extensively proven using NSAID prodrugs. However, the screening of NSAIDs
2-Arylpropionic CXC chemokine receptor 1 (CXCR1) ligands as novel noncompetitive CXCL8 inhibitors
Allegretti, Marcello,Bertini, Riccardo,Cesta, Maria Candida,Bizzarri, Cinzia,Di Bitondo, Rosa,Di Cioccio, Vito,Galliera, Emanuela,Berdini, Valerio,Topai, Alessandra,Zampella, Giuseppe,Russo, Vincenzo,Di Bello, Nicoletta,Nano, Giuseppe,Nicolini, Luca,Locati, Massimo,Fantucci, Piercarlo,Florio, Saverio,Colotta, Francesco
, p. 4312 - 4331 (2007/10/03)
The CXC chemokine CXCL8/IL-8 plays a major role in the activation and recruitment of polymorphonuclear (PMN) cells at inflammatory sites. CXCL8 activates PMNs by binding the seven-transmembrane (7-TM) G-protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2). (R)-Ketoprofen (1) was previously reported to be a potent and specific noncompetitive inhibitor of CXCLS-induced human PMNs chemotaxis. We report here molecular modeling studies showing a putative interaction site of 1 in the TM region of CXCR1. The binding model was confirmed by alanine scanning mutagenesis and photoaffinity labeling experiments. The molecular model driven medicinal chemistry optimization of 1 led to a new class of potent and specific inhibitors of CXCL8 biological activity. Among these, repertaxin (13) was selected as a clinical candidate drug for prevention of post-ischemia reperfusion injury.