α_2C-adrenoceptor modulators: a patent review

Abstract

Introduction: α₂-Adrenoceptors (α₂-ARs) are membrane proteins belonging to the superfamily of GPCRs. Detailed studies have shown three different subtypes, namely α_2A, α_2B and α_2C. Although numerous α₂-AR ligands exist, only a small set of compounds have shown even a degree of selectivity among the three α₂-AR subtypes. Moreover, these compounds suffer from binding to receptor sites outside the α₂-AR subfamily. Efforts made to understand the biological significance of each α₂-AR subtype have greatly been assisted by genetically engineered mice. The main results obtained suggest that α_2C-AR stimulation may represent a therapeutic strategy to get an analgesic response with reduced sedative effects and undesirable changes in blood pressure due to α_2A-AR activation.

Areas covered: This review summarizes the patent literature about the development of α_2C-AR modulators from 2000 to early 2010 and their therapeutic effects evoked by the interaction with this receptor subtype.

Expert opinion: Over 90 patents have been deposited in the last 10 years regarding different methods of α_2C-AR modulation (use of agonists or antagonists, nucleic acids and polypeptides) for diagnosis, prognosis and treatment of disorders involving this receptor. Nevertheless, despite the numerous published patents, ligands highly selective for the α_2C-AR subtype, which continues to be enigmatic, are lacking.

Keywords::

• α_2C-AR agonists
• α_2C-AR antagonists
• α_2C-AR modulators
• α_2C-AR selectivity

Notes

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