title: A new generation of anti-histamines: Histamine H4 receptor antagonists on their way to the clinic.
abstract: At the turn of the millennium, the DNA sequence encoding the histamine H4 receptor (H4R) was identified in data from human genome databases. Considering the clinical importance of H1R and H2R ligands, and the clinical trials that are ongoing for H3R ligands, the latest addition to the histamine receptor family was noted with interest by the pharmaceutical industry. Initial studies describing the expression of the H4R, and the activity of this receptor in (patho)physiology, suggested that the H4R played a role in the immune system. The introduction of the reference H4R antagonist JNJ-7777120 (Johnson & Johnson Pharmaceutical Research & Development LLC/Abbott Laboratories), and proof of the efficacy of this agent in models of asthma, allergic rhinitis and pruritus, highlighted the H4R as a novel drug target. The first clinical candidates targeting the H4R have been identified, and new H4R antagonists are expected to enter the clinic in the near future.
authors.affiliation: Boehringer Ingelheim RCV GmbH & Co KG, Department of Medicinal Chemistry, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Engelhardt
authors.forename: Rogier A
authors.initials: RA
authors.lastname: Smits
authors.forename: Rob
authors.initials: R
authors.lastname: Leurs
authors.forename: Eric
authors.initials: E
authors.lastname: Haaksma
authors.forename: Iwan J P
authors.initials: IJ
authors.lastname: de Esch
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D015195:Drug Design; D055808:Drug Discovery; D006633:Histamine Antagonists / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015394:Molecular Structure; D010879:Piperazines / Q000494:pharmacology; D011537:Pruritus / Q000188:drug therapy / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011968:Receptors, Histamine / Q000378:metabolism; D000074040:Receptors, Histamine H4; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D018926:Anti-Allergic Agents; C418607:HRH4 protein, human; D006633:Histamine Antagonists; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine