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Publication No: CN121646595 [China] Application No: CN202580003857
Title: Agonism-antagonism of endosomal TLR by modulating chemical characteristics of 8-oxopurine
Publication Date: 10-03-2026 File Date: 09-06-2025
Inventor(s): A Tarukdar; D Ganguli; D Carl; S Patanayak; U G Dustidar; P Bandopadhaya; B P Xinha; S Roy; J Sarif; R D Rosario; T Gosh; R Darth
IPC Classification: C07D473/28, A61K31/7076, A61P35/00, C07D473/00, C07D473/32, C07D487/04
Abstract:
Toll-like receptors (TLRs) are an integral part of the innate immune system and play a key role in the recognition and management of microbial pathogens. TLR7, TLR8 and TLR9 are located in endosomal-lysosomal compartments within cells, and are then dedicated to detection of microbial nucleic acids after they are phagocytosed and reach endosomal compartments. The biological importance of TLR agonists is that they can be a powerful tool for studying the innate immune response, developing vaccines and potential therapeutic applications. Furthermore, TLR agonists have been explored as immunotherapies, and antagonists of these TLRs can act as new causative nodes in the context of different autoimmune diseases. Therefore, agonists and antagonists of these endosomal TLRs are of therapeutic interest in different clinical settings. Previous studies on 8-oxo-adenine groups have shown that the C-6-NH 2 group is extremely important for recognition of the agonistic active site and subsequent induction of Interferon (IFN). The present invention explores the ability of 8-oxopurine derivatives which do not contain the requisite C-6 amine groups and are substituted with hydrogen. Substitution of the C-6 amino group with hydrogen (H) in 8-oxopurine derivatives provides exciting insight into the modulation of these endosomal TLRs. The ability of 8-oxopurine derivatives to modulate endosomal TLRs has been reported, the derivatives being related to various substitutions at N-7, N-9 and C-2, all containing a hydrogen at C-6.Structure 1
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