The invention provides novel compounds (adjuvants) that can be used as agonists for Toll-Like Receptor 7 (TLR7). By specifically targeting TLR7, these adjuvants elicit a type 1 interferon response which is essential in the development of antiviral responses.
Toll like receptors are activated by single stranded RNA. Typically, when toll like receptors are non-specifically activated, proinflammatory cytokines are upregulated, which results in adverse side effects.
These small molecule agonists specifically target TLR7. Due to this specificity, these small molecules induce potent anti-viral responses while avoiding inflammatory responses that result from activation of TLR-4, -5 or -8.
Because these small molecules avoid eliciting inflammation they can be used as effective and safe adjuvants.
Derivatives of 1H-imidazo[4,5-c]pyridine were synthesized that are specific for TRL7. Due to this specificity, these derivatives potently induce IFN-alpha in peripheral blood mononuclear cells while having a weak stimulatory effect on proinflammatory cytokines.
These novel TLR7 adjuvants are highly potent in cell based assays. Two of the compounds have an EC50 of 0.075 micro molar. In addition, the adjuvants are water soluble.
These novel small molecule agonists are pure agonists for TLR7. They, therefore, avoid the inflammatory side effects of the non-specific toll like receptor agonists that are currently on the market.