Introduction: Several studies underlined the critical role of histamine H4 receptor (H4R) in inflammation, thus H4 modulators have been suggested as promising drug candidates in inflammatory diseases. First H4 ligands typically have indole or amino-pyrimidine scaffolds. During the last few years, however, serious efforts have been made to identify novel H4 chemotypes with improved pharmacodynamic and pharmacokinetic properties.
Areas covered: Areas covered in this review include an overview on H4 ligands published in scientific papers, as well as in patent applications between 2009 and 2011. Recently discovered scaffolds possessing significant H4 activity were analyzed and their therapeutic potential was reviewed.
Expert opinion: Recent results from the scientific literature and novel patent applications reinforce the major role of H4R in inflammatory diseases such as pruritus, asthma, inflammatory pain and allergic rhinitis. Novel studies suggest further indications of H4 modulators in cancer, neuropathic pain, vestibular disorders and type 2 diabetes. The number of active H4 chemotypes was increased significantly. The first H4 antagonist entered to clinics and the results from a proof-of-concept Phase II clinical study is expected to be disclosed soon.