α2C-adrenoceptor modulators: a patent review.

INTRODUCTION: α2-Adrenoceptors (α2-ARs) are membrane proteins belonging to the superfamily of GPCRs. Detailed studies have shown three different subtypes, namely α2A, α2B and α2C. 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 α2C-AR stimulation may represent a therapeutic strategy to get an analgesic response with reduced sedative effects and undesirable changes in blood pressure due to α2A-AR activation. AREAS COVERED: This review summarizes the patent literature about the development of α2C-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 α2C-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 α2C-AR subtype, which continues to be enigmatic, are lacking.