P2X7 receptor antagonists: a patent review (2010-2015)

The P2X7 receptor (P2X7R) is a unique subtype among the family of seven purinergic P2X receptors, which are ATP-gated non-selective cation channels. P2X7R has been reported to have pathological roles in various diseases, including autoimmune diseases such as arthritis and inflammatory bowel disease, neurodegenerative diseases, chronic pain, mood disorders and cancers. Therefore, many pharmaceutical companies have endeavored to develop a clinical candidate targeting P2X7R. Areas covered: This review provides a summary of various patents on chemicals and biologics and their clinical use published between 2010 and 2015. The reader will gain information on structural claims, representative structures and biological activities of recently developed P2X7R antagonists. Expert opinion: P2X7R is a fascinating therapeutic target and potential biomarker for inflammation, pain disorders and cancers. Research on the development of P2X7R antagonists has continually increased despite the failure of AstraZeneca and Merck's compounds in phase II clinical trials. Various scaffolds have been disclosed by several pharmaceutical industries, and some compounds are currently under investigation in clinical trials.