Functional Profiling of 2-Aminopyrimidine Histamine H4 Receptor Modulators

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• 作者：Mark S. Tichenor ; Robin L. Thurmond ; Jennifer D. Venable ; Brad M. Savall
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：September 24, 2015
• 年：2015
• 卷：58
• 期：18
• 页码：7119-7127
• 全文大小：410K
• ISSN：1520-4804

文摘

Histamine is an important endogenous signaling molecule that is involved in a number of physiological processes including allergic reactions, gastric acid secretion, neurotransmitter release, and inflammation. The biological effects of histamine are mediated by four histamine receptors with distinct functions and distribution profiles (H₁鈥揌₄). The most recently discovered histamine receptor (H₄) has emerged as a promising drug target for treating inflammatory diseases. A detailed understanding of the role of the H₄ receptor in human disease remains elusive, in part because low sequence similarity between the human and rodent H₄ receptors complicates the translation of preclinical pharmacology to humans. This review provides an overview of H₄ drug discovery programs that have studied cross-species structure鈥揳ctivity relationships, with a focus on the functional profiling of the 2-aminopyrimidine chemotype that has advanced to the clinic for allergy, atopic dermatitis, asthma, and rheumatoid arthritis.