title: Histamine H4 receptor ligands: future applications and state of art.
abstract: Histamine is a chemical transmitter found practically in whole organism and exerts its effects through the interaction with H1 to H4 histaminergic receptors. Specifically, H4 receptors are found mainly in immune cells and blood-forming tissues, thus are involved in inflammatory and immune processes, as well as some actions in central nervous system. Therefore, H4 receptor ligands can have applications in the treatment of chronic inflammatory and immune diseases and may be novel therapeutic option in these conditions. Several H4 receptor ligands have been described from early 2000's until nowadays, being imidazole, indolecarboxamide, 2-aminopyrimidine, quinazoline, and quinoxaline scaffolds the most explored and discussed in this review. Moreover, several studies of molecular modeling using homology models of H4 receptor and QSAR data of the ligands are summarized. The increasing and promising therapeutic applications are leading these compounds to clinical trials, which probably will be part of the next generation of blockbuster drugs.
authors.affiliation: Departamento de Ciências Exatas e da Terra, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, UNIFESP, Diadema, Brazil.
authors.forename: Michelle Fidelis
authors.initials: MF
authors.lastname: Corrêa
authors.forename: João Paulo
authors.initials: JP
authors.lastname: dos Santos Fernandes
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D008024:Ligands; D008958:Models, Molecular; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000276:immunology; D011968:Receptors, Histamine / Q000276:immunology; D000074040:Receptors, Histamine H4; D013329:Structure-Activity Relationship
chemical_list: C418607:HRH4 protein, human; D007093:Imidazoles; D007211:Indoles; D008024:Ligands; D011743:Pyrimidines; D011799:Quinazolines; D011810:Quinoxalines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C514526:indole-5-carboxamide; C012180:2-aminopyrimidine; C029899:imidazole
keywords: H4 receptor ligands; QSAR; antihistamines; molecular modeling; structure-activity relationships