The evolution of P2X7 antagonists with a focus on CNS indications

• Published in: Bioorganic & medicinal chemistry letters Vol. 26; no. 16; pp. 3838 - 3845
• Main Authors: Rech, Jason C., Bhattacharya, Anindya, Letavic, Michael A., Savall, Brad M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.08.2016
• Subjects: Animals; Brain penetrant; Central Nervous System Diseases - drug therapy; Central Nervous System Diseases - metabolism; Clinical Trials as Topic; Cytokines - metabolism; Half-Life; Heteroaromatic; Heterocyclic; Humans; IL-1β; Inflammation - prevention & control; Neuroinflammation; P2X7; Protein Binding; Purinergic; Purinergic P2X Receptor Antagonists - chemistry; Purinergic P2X Receptor Antagonists - pharmacokinetics; Purinergic P2X Receptor Antagonists - therapeutic use; Receptors, Purinergic P2X7 - chemistry; Receptors, Purinergic P2X7 - metabolism; Brain penetrant; P2X7; Neuroinflammation; Purinergic; Heteroaromatic; IL-1β; Heterocyclic

[Display omitted] The P2X7 receptor is an ATP-gated nonselective cation channel that has been linked to a number of inflammatory diseases. Activation of the P2X7 receptor by elevated levels of ATP results in the release of proinflammatory cytokines and elevated levels of these cytokines has been ass...