Small molecule antagonists of the CXCR2 and CXCR1 chemokine receptors as therapeutic agents for the treatment of inflammatory diseases.
In the past eight years, numerous series of small molecule CXCR2 and CXCR1 antagonists have been disclosed. These compounds have proved to be effective inhibitors of ELR+ chemokine-induced chemotaxis of neutrophils and other immune cells in vitro and have also been efficacious in several animal models of inflammatory disease. Although some of these compounds have been reported to be in clinical development, no data on clinical studies in patients with inflammatory disease has been revealed to date. This review details the medicinal chemistry and pharmacology of the aforementioned antagonist series.
Busch-Petersen
Jakob
J
GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. Jakob.2.Busch-Petersen@gsk.com
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D015394:Molecular Structure; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors* / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000276:immunology; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B