The human histamine H4 receptor (H4R) is expressed primarily on hematopoietic cells including eosinophils, dendritic cells, and mast cells, and ligand-mediated modulation of H4R has been implicated in inflammatory and immune responses. Correspondingly, antagonists of the H4 receptor have demonstrated activity in numerous pre-clinical models of inflammation. Herein is described the synthesis and SAR investigation that led to the identification of the human H4R antagonist JNJ38518168 from a high-throughput screening hit. This molecule is being studied in human clinical trials for the treatment asthma, rheumatoid arthritis, and psoriasis.

Discovery and optimization of the human histamine H4 antagonist Toreforant (JNJ38518168) for the treatment of inflammatory diseases

249th National Meeting (2015)

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