Document Detail

Recent patents on novel P2X(7) receptor antagonists and their potential for reducing central nervous system inflammation.
MedLine Citation:
PMID:  19705995     Owner:  NLM     Status:  MEDLINE    
Inflammation arises in the CNS from a number of neurodegenerative and oncogenic disorders, as well as from ischemic and traumatic brain injuries. These pathologies give rise to increased levels of extracellular adenine nucleotides which, via activation of a variety of cell surface P2 purinergic receptors, influence the inflammatory activities of responding immune cells. One P2 receptor subtype in particular, the P2X(7) receptor, potentiates the release of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta) from macrophage-like cells. It is also thought to contribute to secondary brain injury by inducing neuronal cell death. Therefore, antagonism of this receptor could have significant therapeutic impact on all disorders, not just CNS, to which excessive inflammatory activities contribute. The use of currently available P2X(7) receptor antagonists for the treatment of CNS inflammation has been limited to the generally non-selective antagonists PPADS, oxidized ATP, Brilliant Blue G, suramin, calmidizolium, and KN-62. However, the recent patents and development of novel P2X(7) receptor antagonists, as discussed in this review, will provide new tools both for clinical and research purposes. Here we discuss compounds for which patents have been applied since 2006, from the following categories: benzamide inhibitors, bicycloheteroaryl compounds, acylhdranzine antagonists, biaromatic P2X(7) antagonists, heterocyclic compounds and amide derivatives, and aromatic amine antagonists.
Scott A Friedle; Marjorie A Curet; Jyoti J Watters
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Recent patents on CNS drug discovery     Volume:  5     ISSN:  2212-3954     ISO Abbreviation:  Recent Pat CNS Drug Discov     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-17     Completed Date:  2010-03-01     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  101265656     Medline TA:  Recent Pat CNS Drug Discov     Country:  United Arab Emirates    
Other Details:
Languages:  eng     Pagination:  35-45     Citation Subset:  IM    
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MeSH Terms
Anti-Inflammatory Agents / chemistry,  therapeutic use*
Encephalitis / drug therapy*
Myelitis / drug therapy*
Patents as Topic*
Purinergic P2 Receptor Antagonists*
Receptors, Purinergic P2 / metabolism
Receptors, Purinergic P2X7
Grant Support
R01 NS049033/NS/NINDS NIH HHS; R01 NS049033-05/NS/NINDS NIH HHS; R25 GM083252/GM/NIGMS NIH HHS; R25 GM083252/GM/NIGMS NIH HHS; R25 GM083252-01/GM/NIGMS NIH HHS; R25 GM083252-04/GM/NIGMS NIH HHS; T32 HL007654/HL/NHLBI NIH HHS; T32 HL007654-23/HL/NHLBI NIH HHS; T32HL007654/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/P2RX7 protein, human; 0/Purinergic P2 Receptor Antagonists; 0/Receptors, Purinergic P2; 0/Receptors, Purinergic P2X7

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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