Abstract
Background: Histamine is a chemical transmitter widely distributed in the human body. It exerts its effects through the interaction with histaminergic receptors (H1R to H4R). The H4R is mainly expressed in hematopoietic cells, especially those involved in immune and inflammatory responses, and thus it is an important target for novel antiinflammatory agents for the treatment of disorders such as asthma, dermatitis, rheumatoid arthritis, peritonitis, inflammatory bowel disease and allergic rhinitis. Current pharmacological therapy for the treatment of such inflammatory disorders includes poorly effective drugs in many cases, also causing important adverse reactions. Accordingly, the development of new drugs has been widely explored, especially those with a different mechanism of action from NSAIDs and corticosteroids.
Discussion: H4R antagonists/inverse agonists have demonstrated potential anti-inflammatory properties and thus several ligands have been reported, showing efficacy in several clinical and preclinical studies. The indolcarboxamides, aminopyrimidines, quinoxalines and quinazolines have been the most critically explored scaffolds to achieve highly selective and potent antagonists/inverse agonists. These derivatives have shown in vivo activity and important contributions for the structure-activity relationship data.
Conclusion: In this paper, a review of the main ligands is undertaken and reported in the literature showing in vivo anti-inflammatory activity and potential therapeutic application.
Keywords: H4 receptor, H4R ligands, H4R antagonists, H4R inverse agonists, antihistamines, inflammation, anti-inflammatory drugs.
Current Organic Chemistry
Title:Targeting the Histamine H4 Receptor: Future Drugs for Inflammatory Diseases
Volume: 22 Issue: 17
Author(s): Michelle Fidelis Correa*Joao Paulo dos Santos Fernandes*
Affiliation:
- Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo, Diadema-SP,Brazil
- Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo, Diadema-SP,Brazil
Keywords: H4 receptor, H4R ligands, H4R antagonists, H4R inverse agonists, antihistamines, inflammation, anti-inflammatory drugs.
Abstract: Background: Histamine is a chemical transmitter widely distributed in the human body. It exerts its effects through the interaction with histaminergic receptors (H1R to H4R). The H4R is mainly expressed in hematopoietic cells, especially those involved in immune and inflammatory responses, and thus it is an important target for novel antiinflammatory agents for the treatment of disorders such as asthma, dermatitis, rheumatoid arthritis, peritonitis, inflammatory bowel disease and allergic rhinitis. Current pharmacological therapy for the treatment of such inflammatory disorders includes poorly effective drugs in many cases, also causing important adverse reactions. Accordingly, the development of new drugs has been widely explored, especially those with a different mechanism of action from NSAIDs and corticosteroids.
Discussion: H4R antagonists/inverse agonists have demonstrated potential anti-inflammatory properties and thus several ligands have been reported, showing efficacy in several clinical and preclinical studies. The indolcarboxamides, aminopyrimidines, quinoxalines and quinazolines have been the most critically explored scaffolds to achieve highly selective and potent antagonists/inverse agonists. These derivatives have shown in vivo activity and important contributions for the structure-activity relationship data.
Conclusion: In this paper, a review of the main ligands is undertaken and reported in the literature showing in vivo anti-inflammatory activity and potential therapeutic application.
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Cite this article as:
Correa Fidelis Michelle*, dos Santos Fernandes Paulo Joao*, Targeting the Histamine H4 Receptor: Future Drugs for Inflammatory Diseases, Current Organic Chemistry 2018; 22 (17) . https://dx.doi.org/10.2174/1385272822666180710144636
DOI https://dx.doi.org/10.2174/1385272822666180710144636 |
Print ISSN 1385-2728 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5348 |
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