Uracil derivatives as non-nucleoside inhibitors targeting HIV-1 reverse transcriptase

HIV-1 infection remains a global health challenge, and the development of new antiretroviral agents is crucial to combat drug resistance and improve treatment efficacy. Uracil, as an endogenous nitrogenous base and privileged heterocyclic scaffold, has attracted considerable attention due to its unique chemical structure and the inherent potential to form hydrogen bonds. Over the past decade, uracil derivatives have emerged as potential HIV-1 non-nucleoside inhibitors (NNIs), inhibiting the function of the polymerase domain as HIV-1 NNRTIs and HIV RT-associated RNase H domain, and playing a significant role in the development of more effective and durable antiretroviral therapies. This review provides a brief overview of uracil derivatives as NNIs targeting HIV-1 reverse transcriptase (RT) over the past decade, affording valuable references for the future development of effective HIV-1 inhibitors.