The human immunodeficiency virus (HIV) has infected millions of people worldwide. In spite of many classes of effective antiviral drugs on the market, this virus is still a global pandemic due to the continued emergence of viral resistance to current drugs. The nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are one of the most used classes of drugs in antiretroviral therapy (ART). NRTIs and NNRTIs will inhibit reverse transcriptase (RT) enzyme, causing termination of the growing viral DNA chain. Although these drugs have been proven effective clinically, they have several drawbacks when used in long-term treatment regimes. Some of these drugs have relatively low bioavailability and require phosphorylation by human and/or viral kinases to become activated.<br/> <br/>Boronic acids and their derivatives have recently emerged as biologically interesting moieties, with increased attention in their use as pharmaceutical agents. In this research, we will investigate nucleoside boronic acids and their derivatives as potential NRTIs for HIV treatment. It is hypothesized that the incorporation of the boronic acid moiety will improve cellular permeability and pharmacological properties due to their lower negative charge compared to the current nucleoside analogs which incorporate phosphonate moieties. Herein, we report on the synthesis of borono-nucleoside analogs with various boronic acid warheads and varied linker lengths to support expanded structure activity relationship studies. Subsequently, these compounds will have their biological activity against HIV determined.

Synthesis of borono-nucleoside analogs with potential use as anti-HIV agents

ACS Spring 2022

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