Phenol-containing antagonists of the CXCR2 receptor

Background: ELR+ chemokines interact with the CXCR2 receptor on neutrophils and other immune cells to induce chemotaxis. This event plays a key role in a large number of autoimmune diseases and thus antagonists of the CXCR2 receptor have garnered considerable interest in the pharmaceutical industry during the past decade and a half. Objective: The objective of the article is to review recent developments in the patent literature related to the phenol-containing antagonists. Method: Although many other chemotypes have emerged since the first disclosure of phenol-containing antagonists, this compound class is by far the most successful, having yielded all but one of the clinical candidates reported so far, and thus the scope of this review is limited just this antagonist type. Conclusion: During the past few years, phenol-containing CXCR2 antagonists have evolved from promising leads to clinical candidates, and structural diversity within the class has been expanded. Lead compounds have now entered patient studies and will be of great importance not just for this compound class, but also for the therapeutic viability of CXCR2 antagonists in general.