Synthesis and evaluation of 8-substituted adenine derivatives as toll-like receptor 7 agonists.
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Seifert, Zacharie J.
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Toll-like receptors (TLRs) are immune cell receptors that have the ability to recognize microbial pathogens and trigger innate immune responses. Research into TLR7 agonists is of specific interest because they can induce interferon (IFN) production without producing proinflammatory responses. In an ongoing study to synthesize small molecules that act as TLR7 agonists, several 9-benzyl-2-butoxyadenine derivatives with various substitutions at the 8-position have been prepared through a multi-step synthetic route. Utilizing the 8-bromoadenine derivative, both amine and thiol substitutions were performed. The 8-thioadenine derivative was then used to perform nucleophilic substitutions of numerous alkyl halides. These compounds were functionalized for their conjugation to a protein with the use of a protein linker while maintaining immune stimulatory activity.